Compounds containing a Spiro Phosphorus Atom

12.21 Compounds containing a Spiro Phosphorus Atom N. A. Williams Kingston University, Kingston upon Thames, UK ª 2008 Elsevier Ltd. All rights reserved. 12.21.1

Introduction

1066

12.21.2

Theoretical Methods

1077

12.21.3

Experimental Structural Methods

1078

12.21.3.1

X-Ray Diffraction

1078

12.21.3.2

Magnetic Resonance

1079

12.21.3.2.1 12.21.3.2.2

NMR spectroscopy Electron spin resonance spectroscopy

1079 1082

12.21.3.3

Mass Spectrometry

1082

12.21.3.4

Electronic Spectroscopy, Circular Polarization, and Polarimetry

1082

12.21.3.5

Infrared Spectroscopy

1082

12.21.4

Thermodynamic Aspects

1082

12.21.5

Reactivity of Fully Conjugated Rings

1083

12.21.6

Reactivity of Nonconjugated Rings

1083

12.21.6.1

Spirophosphonia Compounds

1083

12.21.6.2

Spirophosphoranes

1084

12.21.6.3

Spiroperphosphoranides

1086

12.21.7

Reactivity of Substituents Attached to Ring Carbon

12.21.8

Reactivity of Substituents Attached to Ring Heteroatoms Including Spiro Phosphorus

12.21.9 12.21.9.1

12.21.9.2

1095 1095 1098

From One Monocyclic Component

1100 1100 1106 1110

Spirophosphoranes Spirophosphoranides Spirophosphoranes Spiroperphosphoranides

1116 1116 1116

By ring modification

1117

Spirophosphonia Spirophosphoranes

1117 1117

Other Methods

12.21.9.6.1 12.21.9.6.2

1111 1111 1114

By [2þ2] Cycloaddition to Phosphorus

12.21.9.5.1 12.21.9.5.2

12.21.9.6

Spirophosphonia compounds Spirophosphoranes Spiroperphosphoranides

By [4þ2] Cycloaddition to Phosphorus

12.21.9.4.1 12.21.9.4.2

12.21.9.5

1095

Spirophosphonia compounds Spirophosphoranes Spiroperphosphoranides

12.21.9.3.1 12.21.9.3.2

12.21.9.4

1095

All Components Acyclic

12.21.9.2.1 12.21.9.2.2 12.21.9.2.3

12.21.9.3

1087

Ring Syntheses

12.21.9.1.1 12.21.9.1.2 12.21.9.1.3

1087

1117

Spirophosphoranes Spiroperphosphoranide

1117 1117

1065

1066 Compounds containing a Spiro Phosphorus Atom 12.21.10 12.21.11

Critical Comparison of Routes to Compounds Containing a Spirocyclic Phosphorus Atom

1121

Important Compounds and Applications

1121

12.21.11.1 12.21.11.2 12.21.12

Nonmedical Applications

1121

Compounds of Medical Interest

1122

Further Developments

References

1122 1122

12.21.1 Introduction This chapter reviews compounds that are spiro fused with a phosphorus atom at the junction of the rings. A spiro compound has at least two rings which have only one atom in common and are not linked by a bridge. The rings may form part of other ring systems. The spirocyclic phosphorus atom may be four, five, or six coordinate, unlike spirocyclic nitrogen atoms that by necessity are always four coordinate. A greater range of compounds with a spiro phosphorus is therefore possible. Spirophosphonia compounds, for example, spirophosphonium salts 1 and ylides 2 have four-coordinate phosphorus. Four-coordinate phosphorus may also be anionic as in spirophosphoranides 3. Spirophosphoranes with five-coordinate spiro phosphorus are particularly well known (4). Six-coordinate spiro phosphorus compounds may be anionic (5) and should be named spiroperphosphoranides according to IUPAC rules, and not phosphates as has been the case in the past. The six-coordinate state allows the formation of a third ring, to give tricyclic species such as 6. Further structural variation is possible if bridges are introduced to the spiro rings, leading to phosphorus analogues of fenestranes 7 and hexacyclic 8 and tetracyclic 9 six-coordinate compounds. Examples are also known where the spiro phosphorus atom is also a bridgehead atom 10. Phosphoranes, phosphines, and phosphine oxides which have donor functional groups that can undergo dative bonding with the phosphorus center may complete a spiro system 11. Such compounds are included in this chapter.

Compounds containing a Spiro Phosphorus Atom

The first seven-coordinate phosphorus compound, 12, containing a spiro phosphorus atom has recently been reported <2000IC1338>. The IUPAC recommendations for the nomenclature of spiro compounds was revised and extended in 1999 <1999PAC531>. The range of cyclic systems for four-, five-, and six-coordinate compounds synthesized up to 1995 is summarized in <1996CHEC-II(8)1135>. This chapter aims to review advances in synthesis, characterization, reactivity studies, and applications of compounds containing a spiro phosphorus atom since 1995. Tables 1–7 give representative examples, reported since 1995, of the major classes compounds containing a spiro phosphorus atom. The subdivision of classes of compounds is that used in CHEC-II(1996); the compounds are grouped according to the number and type of heteroatoms bonded to the spiro phosphorus atom. The labels k, l, m, and n represent the sizes of the spiro rings.

1067

1068 Compounds containing a Spiro Phosphorus Atom

Table 1 Phosphoniaspiro compounds m

n

P-bound

Compound

Reference

4 4 4 4 4 4 4 5 5 5 5 5 5 6 6 6 6 7

4 4 4 5 7 7 7 5 5 5 5 5 6 5 5 6 7 7

CNO2 N4 N2O2 N3O CNO2 CNO2 N2O2 N3O N2O2 N2O2 N4 N4 and N2O2 N2O2 N2O2 N2O2 N4 N4 N2O2

13 14: 14: 15 16: 16: 17: 18 19 20 21 22 23 24 25 26: 27 28

2005ARK102 1996RJC1418 1996RJC1418 2004ICC842 2002CC40 2005JCD1847 2004JOC1880 2004ICC842 2005EJI1042 2004EJO1881 2002JCD365 2006POL953 1999IC5457 2006POL963 1999EJI1673 1999JCD891 1999JCD891 1999JCD891

X ¼ NBu; R ¼ Me, Ph X ¼ O; R ¼ Me, Ph X¼O X¼S R ¼ Me, Et

X ¼ F, Cl

Compounds containing a Spiro Phosphorus Atom

1069

1070 Compounds containing a Spiro Phosphorus Atom

Table 2 Spirophosphorane compounds m

n

P-bound

Compound

Reference

3 3 3 3 4 4 4 4 4 4 4 4 3 4 4 4 4 4 4 4 4

3 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 5 5 5 5 5

N4 N3P N2O2 N2O2 N2O2 NO3 O4 O4 O4 O4 O4 O4 N2O2 N2O2 O4 O4 O4 N2O2 N2O2 O3Re NO2Rh

29 30 31: R ¼ Et, Ph 32 33: R ¼ H, But 34: R ¼ Me, Pri, Bui, Bn 35 36 37 38 39 40: R ¼ Me, Ph 41 42 43 44 45 46: R ¼ Bn, p-FC6H4CH2 47: R ¼ H, ClCH2CH2 48 49

1997ZFA(623)1325 1997ZFA(623)1325 1999IC1093 1996PS493 2000HAC11 1998S376 1997PS419 1997IC2044 1999RJC333 2002PS1255 1997TL1615 2000RJC708 2003POL843 1998RJC530 2003PS2117 2000POL63 1997IC2044 2000ZFA412 1996CB725 2000POL2667 2000JOM418

Compounds containing a Spiro Phosphorus Atom

Table 3 Spirophosphoranes m

n

P-bound

Compound

Reference

4 4 4 4 4 4 4 4 4 5 6

6 6 6 7 7 7 7 7 7 6 6

O4 O4 O4 NO3 NO3 O4 O4 O4 O4 O4 O4

50 51 52 53: 54: 55 56 57 58: 59 60:

1997IC2044 2000POL63 2000POL63 2006NJC717 2006NJC717 1996JA9841 1996IC6552 1995IC4525, 1996IC6552 1996IC6552 2000POL63 1997IC2044, 2000POL63

X ¼ NCS, N3, Cl, NHMe X ¼ NCS, N3, Cl, NHMe

R ¼ Me, Ph R ¼ Me, C6H11

1071

1072 Compounds containing a Spiro Phosphorus Atom

Table 4 Spirophosphoranes with carbon-bonded phosphorus m

n

P-bound

Compound

References

3

3

C2O2

3 3 3 3 3 3

4 4 4 4 4 4

C3 O C2NO C2NO C2O2 C2O2 C3 O

3

4

C2NO

1997AGE2500 1997PS379 2001TL4417 1996PS489 1996PS489 2002JA7674, 2002HAC390 2002JA7674, 2002HAC390 1999CC1423 2000T4823, 2001TL4417 2002HAC97

4 4 4 4 4

4 4 4 4 4

C2O2 C2O2 C2O2 C2O2 C2O2

4 4

4 4

C2O2 N4

61: R ¼ Me R¼H 62 63 64 65 66 67: R1 ¼ But, R2 ¼ Me R1 ¼ R2 ¼ Pri 68: R1 ¼ Me; R2 ¼ H; R3 ¼ Me R1 ¼ R2 ¼ (CH2)3; R3 ¼ CF3 69: R ¼ Me, Bu, Bn 70: R ¼ Me, Bu, Bn 71 72 73: X ¼ OMe, COMe, SMe, NMe2 X ¼ R ¼ Me, n-Bu 74 75

1998JA6848 1998JA6848 2002JA13154 1997TL7753, 2002CL170 2002JOM441 1997TL4107 2001IC6229 1996T2995

Compounds containing a Spiro Phosphorus Atom

Table 5 Spirophosphoranes with a bridgehead phosphorus m

n

P-bound

Compound

Reference

4 4 4 4 4 4 4 4 4

5 5 4 4 5 5 15þ 4 4

CO3 CO3 N2O2 N2O2 N2O2 N2O2 NO3 N2O2 N2O2

76 77: R ¼ Me, Ph 78 79: R ¼ Me, Et, Pri, But, Ph 80: R ¼ Bn, p-FC6H4CH2 81 82: X ¼ O, S, NMe, OC2H4O, OC3H6O 83 84

1998HAC173 1997JFC129 1997PS5 1999OM915, 1997CCL629 1997JFC109 1997CB819 1996PS51, 1995PS199 1997PS5 1997PS5

1073

1074 Compounds containing a Spiro Phosphorus Atom

Compounds containing a Spiro Phosphorus Atom

Table 6 Spirophosphoranides and other hexacoordinate phosphorus compounds containing a spiro phosphorus l

m

n

P-bound

Compound

References

4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4

4 4 4 4 4 4 4 4 4 4 4 3 4 4 4 5 6 4 4

6 4 4 4 4 4 4 4 6 3 3 3 3 2 5 6 6 6 5

O6 O6 O6 O6 O6 O6 O6 O6 O6 C3O3 C3O3 CN3O2 CN3O2 C2O4 N4S NO5 NO5 NO5 NO5

85 86: X ¼ H, Br 87: R ¼ Me, Et, Pri, But 88 89 90: X ¼ H, Y ¼ F; X ¼ F, Y ¼ H 91: X ¼ N, CH 92: R ¼ Me, Ph 93 94: R ¼ Me, Ph, CF3 95 96 97: R ¼ Me, Et 98 99 100 101 102 103

2000OL4185 2002JOM392 2002HCA1364 1997AGE608 2002OL2309 2005AGE5060 2002EJO3580 2002EJO3580 2002EJO3580 1997TL547, 1997TL551 2002JA13154 1996PS493 1996PS493 1999JA6958 1996IC6899 1996JA9841 1996JA9841 1996JA9841 1996JA9841

1075

1076 Compounds containing a Spiro Phosphorus Atom

Table 7 Hexacoordinate phosphorus compounds containing a spiro phosphorus m

n

P-bound

Compound

References

4 4 4 4 4 4 4 5 5 4

4 4 4 4 4 4 5 5 5 4

O2P2 NO2S N2O2 O3S O3S O3S O4 N4 N4 C2N2

104 105 106 107: X ¼ Cl, NMe2, OC6H5 108: X ¼ Cl, NMe2, OC6H5 109 110 111 112: R ¼ OH, OEt, NEt2 113

1998AGE1098 2004JOC1880 1998RJC530 1997JA1317, 1998IC3747 1997JA1317, 1998IC3747 1997IC5730, 1997JA11434 1997IC2578 2001IC5553 2001IC5553 1999IC1336

Compounds containing a Spiro Phosphorus Atom

12.21.2 Theoretical Methods Molecular mechanics calculations using HyperChem software showed that for 56 and 58 (R ¼ Et, Ph), the structures with the eight-membered ring in a diequatorial position are of lower energy than the isomeric structures with the ring in an apical–equatorial orientation. This is in agreement with X-ray crystallography studies. Conversely, the calculations predict the correct geometry of 57, in which the eight-membered ring adopts an apical–equatorial position. This suggests the tert-butyl groups are responsible for favoring the diequatorial position <1996IC6552>. Density functional theory (DFT) calculations at the hybrid B3PW91 level indicate the presence of a low-lying * P–Oequatorial orbital for the O-cis isomer 69, which accounts for its greater reactivity toward nucleophiles compared with the transisomer 70. Reactions with the trans-isomer were shown to involve a higher energy * P–Cequatorial orbital <2002PS1671, 2002JA13154>. Experimental and semi-empirical AM1 studies demonstrate that 79 exists as two diastereomeric, trigonalbipyramidal species in equilibrium with a square planar transition state. In this case, AM1 calculations were more successful than a more rigorous study at DZP/SCF level of theory <1999OM915>. AM1 calculations have also been performed on macrocyclic spirophosphoranes 174 <2001PS177>. PM3 semi-empirical calculations on 67 supported the experimentally observed formation of the [2þ2] cycloaddition product rather than a [4þ2] Diels–Alder cycloadduct. The calculations indicate that the oxaphosphete ring is

1077

1078 Compounds containing a Spiro Phosphorus Atom ˚ <2000T4823>. Optimization of the geometry of 67 by AM1 semihighly strained with a very long P–O bond (1.99 A) empirical calculation leads to the opening of the strained four-membered ring <2001TL4417>. The equilibrium interconversion between an ethylene phosphite and a bicyclic spirophosphorane is shown to proceed by the insertion of the phosphite into the labile O–H bond of the hydroxyethyl ester. The mechanism is similar to the insertion of carbenes or nitrenes. Energy relationships of reaction intermediates were studied by MO RHF, MP2(full), MP4SDTQ, and DFT calculations. In most cases, they predicted that hydroxyethyl ethylene phosphates were more stable than the strained spirophosphoranes, which is not supported by the experimental evidence. The best correspondence to experimental data was obtained by DFT calculations with Perdew–Wang correlation functions <2003JST35>.

12.21.3 Experimental Structural Methods 12.21.3.1 X-Ray Diffraction The relative preference of substituents for the apical position in trigonal bipyramidal phosphoranes is known as apicophilicity and depends on the electronegativity of the substituent, steric factors, and p-donor effects. Small, highly electronegative substituents normally display high apicophilicity. In spirophosphoranes, ring constraints can play a more important role in controlling the apical site occupancy. For example, in spirophosphoranes with four- to seven-membered rings, normally each ring of the spirocyclic system prefers to occupy one apical and one equatorial site, leaving the monodentate ligand to occupy the remaining equatorial site, irrespective of the electronegativity of the substituent. Compound 58 (R ¼ Ph) was the first example of a spirophosphorane in which the least electronegative group, in this case the phenyl group, occupies the axial site, leaving both oxygens of the eight-membered ring to occupy two equatorial positions. <1995IC4525>. The ethyl and chloro derivatives 58 (R ¼ Et, Cl) also display reverse apicophilicity <1996IC6552, 2002POL1155>. Employing electron-withdrawing chlorine substituents instead of tert-butyl groups on the aromatic groups that make up the eight-membered phosphocin ring leads to the large ring occupying the more conventional axial–equatorial positions and the phenyl group occupying an equatorial site to give 57. This suggests that steric repulsions involving the tert-butyl groups are responsible for the eight-membered ring favoring a diequatorial arrangement at the phosphorus center <1996IC6552>. Numerous structural studies demonstrated that with the sterically hindered eight-membered ring axial–equatorial and equatorial–equatorial arrangements were both feasible <1996JA9841, 1996IC6552, 1997IC2044, 2000JA964. 2002JOC6653, 2006ACR324>. Small variations in substituents are sufficient to favor one isomer; for example, primary amide groups display normal apicophilicity in the formation of 117 while secondary amide groups display reverse apicophilicity in forming 116 <2000JA964, 2002IC2356>. X-Ray studies also reveal that the eight-membered ring adopts a boat-chair conformation when it spans two equatorial positions but adopts a distorted tub formation when it takes up an apical–equatorial position. It is clear that apical bonds are longer than equatorial bonds in pentacoordinate spirophosphoranes. This is demonstrated in 69 (R ¼ Bu), where P–Oapical ¼ 1.768 A˚ > P–Oequatorial ¼ 1.659 and P–Capical ¼ 1.863 A˚ > ˚ while for the apicophilic isomer 70 the pairs of bond distance are very similar, for example, P–Cequatorial ¼ 1.813 A, P–Oapical ¼ 1.753 and 1.765 A˚ <1996JA12866>. This is consistent with 3c-2e bonds for apical substituents and 2c-2e bonds for equatorial substituents. Similar behavior is seen in oxaphosphetane ring of 65 and 66 where for P–Capical ¼ 1.914 A˚ > P–Cequatorial ¼ 1.82 A˚ and P–Oapical ¼ 1.745 A˚ > P–Oequatorial ¼ 1.663 A˚ <2002JA7674>. The ˚ P–N bond in 116 and 117 is also significantly longer when the nitrogen occupies an apical position (1.76 and 1.67 A) ˚ than when it is equatorial (1.63 and 1.58 A) <2000JA964, 2002IC2356>. Eight-membered rings exhibit shorter P–O bond lengths than five-membered rings as a result of less strain, for example, for 57 P–Oapical bond length for eightmembered ring ¼ 1.661 A˚ compared to P–Oapical ¼ 1.747 A˚ for the five-membered ring <1996IC6552>. Five-membered ring systems have also shown anti-apicophilicity with carbon occupying an apical position in favor of oxygen 69. In this case, the ring still maintains an axial–equatorial disposition <1996JA12866, 2001OL1873>. Antiapicophilic spirophosphoranes 65 bearing a four-membered oxaphosphetane ring have been structurally characterized along with its apicophilic isomer 66 <2002JA7674>. Five-coordinate spirophosphoranes usually adopt a trigonal bipyramidal structure distorted along the Berry pseudorotation coordinate toward a square pyramidal structure in which the two rings occupy the four basal sites. A method for determining percentage distortion of the trigonal bipyramidal structure based on the dihedral angles is commonly employed. Distortion percentages reported include 11% for 118 and 119 <1997IC2044>, 22–26% for 120 <2001RJC330>, and 8–20% for 69 and 70 (R ¼ Bu, But, 2,4,6-(Pri)3C6H2 <2006EJO2739>.

Compounds containing a Spiro Phosphorus Atom

Studies of diastereomers of 61 indicate that the cis–cis- and the cis–trans-isomers have distorted (20%) TBP structure, whereas the trans–trans-isomer has a distorted square pyramidal structure <1997AGE2500>. X-Ray crystallographic investigations of 73 bearing COMe and NMe2 groups reveals p-conjugation interactions involving the phosphorus <2002JOM441>. X-Ray studies have been critical to confirming hexacoordination in structures 107–109, which contain a sulfur donor group incorporated into an eight-membered phosphocin ring. These compounds were shown to have octahedral geometries distorted toward a square pyramidal geometry. The octahedral character was estimated as 65% for 109 <1997IC5730> but as low as 24% for 108 (X ¼ NHBn) due to the presence of p-backbonding from the NHBn group <1997JA1317>. Electron-withdrawing groups on the aryl ligands increase the donor action and the percentage octahedral character for 107 and 108 (X ¼ OC6F5) <1998IC3747>. Analogous compounds 110 containing sulfonyl groups exhibit P–O donor action but less octahedral character than 107 <1997JA11434, 1997IC2578>. Hydrogen-bonding interaction between the NH proton and the apical oxygen lead to dimer formation in 44 and a chain structure for 59 (R ¼ Me) <2000POL63>. Extensive hydrogen bonding is seen in 121 leading to a linear polymeric structure <2001IC6229>. The carboxylate form 122 also displays hydrogen bonding, but in this case it involves interaction with ammonium ions <2002IC1645>. A range of spiro derivatives, 21 and 22, of the spermine-bridged bis-cyclotriphosphazene have been structurally characterized by X-ray crystallography and had their absolute configuration determined <2002JCD365, 2003JA4943, 2004AXB739>. Generally, the cyclophosphazene ring remains planar and the spiro ring adopts a chair or twisted chair conformation. The effect of electron-withdrawing substituents on the electron supply to the cyclophosphazene ring was analyzed from crystallographic data <2006POL953>. Many other cyclophosphazene-containing spirophosphonia have been subject to absolute structure determination allowing the correct assignment of chiral centers <1999EJI1673, 2004CEJ4915, 2004ICC657, 2004ICC842, 2004EJO1881, 2004JST139, 2006JCD1302>. Phosphonium salts 1 (m ¼ n ¼ 4) were shown to have tetrahedral geometry with small endocyclic C–P–C bond angles 97–98 <2002JA6126>. The octahedral geometry of spirophosphoranides allows the formation of chiral species, if three bidentate ligands are coordinated. The configurationally stable TRISPHAT anion 88 was prepared in enantiomerically pure form and was shown to have a near-perfect octahedral geometry. An absolute P configuration was confirmed by X-ray crystallography <1997AGE608>. X-Ray analysis revealed the BINPHAT anions 85 derived from (R)-BINOL to have an (, R) configuration <2000OL4185> whereas the major diastereomer of BINOTROP 89 made from (R)-BINOL had a (
, R) configuration <2002OL2309>. Fluorinated TRISPHAT derivatives 90 were shown to have an absolute
configuration <2005AGE5060> and TARPHAT 87 a  2R, 3R configuration <2002HCA1364>. Hexacoordinate 98 containing a three-membered PO2 ring was characterized by X-ray crystallography <1999JA6958>.

12.21.3.2 Magnetic Resonance 12.21.3.2.1 31

NMR spectroscopy

P nuclear magnetic resonance (NMR) spectroscopy has been of great use in determining the coordination state and stereochemistry of the phosphorus atom at the spiro position in spirophosphonia compounds, spirophosphoranes and spiroperphosporanides. The 31P chemical shift is also sensitive to the nature of the atoms directly bonded to the spiro phosphorus center and the size of rings of the spirocyclic system. Four-coordinate spirophosphonium ylides display 31P chemical shifts that are further downfield to those seen in pentacoordinate spirophosphoranes with similar ligands. It is noted that large rings can have a considerable shielding effect as seen for systems containing eight-membered rings, for example, 18 (m ¼ 7; n ¼ 7), P ¼ 25 ppm; 19 (m ¼ 5, n ¼ 7), P ¼ 14 ppm; and 21 (m ¼ 5, n ¼ 5), P ¼ 6.3 ppm <1999JCD891>. Small rings have an opposite deshielding effect, for example, 14 (m ¼ 4, n ¼ 4), P ¼ 28 ppm <1996RJC1418>. Certain spirophosphonium ylides display signals further downfield, for example, 16 (m ¼ 4, n ¼ 7), P ¼ 62 ppm <2005JCD1847>. Obviously, the nature of the groups bound to the phosphorus play an important role as well. 31 P NMR and a chiral solvating agent, (S)-(þ)-2,2,2,-trifluoro-1-(99-anthryl)ethanol, has been used to determine the stereogenic properties of spirophosphonium ylides <2002JCD365, 2004ICC657, 2004ICC842, 2004EJO1881, 2005EJI1042, 2006JCD1302>. Chiral shift reagents have also been used to help characterize the chiral properties of similar molecules <2000JA12447, 2002JCD365>. It has been noted that more NMR signals than would be predicted may observed on adding chiral shift reagents or chiral solvating agents to a solution of spermine-bridged cyclophosphazenes. This anomalous behavior is only seen for the meso-forms and is explained by a complexation equilibrium of the chiral ligand with the meso-compounds <2003JA4943>.

1079

1080 Compounds containing a Spiro Phosphorus Atom 31

P NMR chemical shift data for a series of tetraoxyamino-spirophosphoranes demonstrates that five- and sevenmembered rings deshield phosphorus relative to six- and eight-membered rings <1997IC2044, 2000POL63, 2002POL1155, 2002IC2356>, for example, 123 (m ¼ 7, n ¼ 5), P ¼ 70 ppm, 124 (m ¼ 7, n ¼ 6), P ¼ 59 ppm, 117 (X ¼ NC6H11, m ¼ 7, n ¼ 4), P ¼ 55 ppm, 52 (m ¼ 6, n ¼ 4), P ¼ 37 ppm, 45 (m ¼ 5, n ¼ 4), P ¼ 46 ppm, 50 (m ¼ 4, n ¼ 4), P ¼ 28 ppm. In the related anti-apicophilic structures with the amino group occupying the apical position, the 31 P NMR signal is shifted downfield, for example, 116 (X ¼ N(Pri)2, m ¼ 7, n ¼ 4, p ¼ 41.9 ppm). Similar chemical shifts are seen for spirophosphoranes bearing Martins ligands 69 and 70 <1996JA12866, 2002JOM441>. The pseudorotation between enantiomers of 70 <1996JA12866> and between diastereomers of 73 <2002JOM441> was studied by 19 F and 31P NMR spectroscopy. The rate of cyclization of 125 (R ¼ Bu) to 70 and 125 (R ¼ tert-Bu) to 70 has been monitored by 19F and 31P NMR spectroscopy <1996TL8409, 2006EJO218>. The stereomutation mutation of O-cisarylspirophosphoranes 69 (R ¼ Aryl) to the O-trans-isomer 70 could also be followed by NMR spectroscopy <2006EJO2739>. Activation parameters for stereomutation were estimated from Eyring plots derived from NMR data and used to determine the apicohilicity of groups in spirophosphoranes <2002JOM441>. The order derived was OMe, H > COMe, SMe, NMe2 > Me > Bu. In contrast, NMR spectroscopy reveals that the greater electronegativity of substituents in tetraoxyspirophosphoranes results in solution structures that are rigid at room temperature <1996IC6552>.

Compounds containing a Spiro Phosphorus Atom

Variable-temperature NMR spectroscopy has been widely used to study a variety of intramolecular rearrangements of spirophosphoranes. The 31P NMR spectrum of 116 (X ¼ NMe2) at 233 K in toluene reveals two signals of equal intensity ( 42.3, 43.1 ppm) and an upfield signal ( 47.1 ppm). As the temperature is raised, the two downfield signals coalesce; this is attributed to a boat-chair $ tub conformation isomerism of the NMe2 axial isomer 116 (Equation 1). At higher temperature, the upfield signal broadens and then disappears. This signal is attributed to the eight-membered ring in the NMe2 equatorial isomer undergoing an exchange between axial–equatorial coordination and an equatorial–equatorial coordination (Equation 2), hence forming the NMe2 axial isomer <2000JA964, 2002IC2356>.

ð1Þ

ð2Þ

The difference in chemical shift can be attributed to a significant change to the local environment of the phosphorus where the O–P–O angle may change from 95 to 117 and changes in P–N bond lengths can be expected. Low-temperature NMR has indicated the presence of more than two isomers for related compound 117 (R ¼ Me and Et) when in solution <2004OL145>. Compound 54 in toluene also exhibits three peaks in the pentacoordinate phosphorus region of the 31P NMR spectrum at 298 K. A weak signal at  39.5 is seen to grow significantly and a pair of signals ( 60.1, 60.4 ppm) are seen to coalesce and then diminish in intensity as the temperature is raised. The coalescing upfield signals are attributed to a boat-chair and tub conformation exchange of the eight-membered ring in 54. The increase in the lowfield signal is assigned to the isomerization of 54 to structure 126 (Equation 3), which displays normal apicophilictity with the two nitrogen groups occupying equatorial positions. <2002JOC6653>. The related compound 54 (X ¼ N3) exhibits two peaks in the 31P NMR spectrum at 298 K ( 61.0 and 69.7 ppm); on the basis of the chemical shift difference, the signals were tentatively assigned to the N3 apical and equatorial isomers rather than isomers derived from a rearrangement of the five-membered ring.

ð3Þ

1 H{15N} double resonance and two-dimensional (2-D) 15N/1H heteronuclear correlation (HETCOR) experiments were used to determine the signs of phosphorus 1J and 2J coupling constants for spirophosphoranes 33 derived from aminophenols. Isotope-induced chemical shifts were also measured, using an INEPT-HEED pulse sequence <2000HAC11>. The sign of spin coupling constants was also obtained for 29 and 30 by analysis of cross multiplets in the 2-D 13C and 1H correlation spectroscopy (COSY) and correlation through long-range coupling (COLOC) spectra <1997ZFA1325>. Hexacoordinate, tricyclic spirophosphoranides, 88 <1997AGE608, 2004JOC8521>, 89 <2002OL2309>, 91 and 92 <2002EJO3580>, bearing only diolato ligands typically display 31P chemical shifts in the  77 to 82 ppm region, whereas spirophosphoranides 94 and 95 bearing an oxphosphetane ring exhibit 31P signals in the  110 to 120 ppm region <1997TL547, 2002JA13154>.

1081

1082 Compounds containing a Spiro Phosphorus Atom 1

H and 19F NMR demonstrates an intraconversion between hexacoordinate and pentacoordinate structures for 110 revealing the donor interaction of the sulfonyl group to be labile <1997JA11434, 1997IC2578>. Other hexacoordinate structures 107 and 108, with donor interactions, maintain their coordination geometry in solution <2002IC1645>. 1H NMR reveals that hexacoordinate 113 undergoes an intramolecular 1,2 shift of ligands <1999IC1336>. 1H homodecoupling measurements suggested a rapid exchange process involving the oxaphosphetane ring in spirophosphoranide intermediate 94 <1997TL547>.

12.21.3.2.2

Electron spin resonance spectroscopy

Electron spin resonance (ESR) indicates that the single electron reduction of phosphorus porphyrin derivatives 112 gives porphyrin p-anion radicals as the main products. Spectral line widths suggest an interaction between the unpaired electron on the porphyrin ring and the central phosphorus atom <2001IC5553>. The phosphaverdazyl radical 127 has been investigated by ESR and electron–nuclear double resonance (ENDOR). The results suggest that spin density is transferred from the verdazyl ring to the phosphazene ring <2002CJC1501, 2004CJC1119>.

12.21.3.3 Mass Spectrometry Fragmentation of amino acid-derived spirophosphorane 128 has been analyzed using field desorption (FD), EI, and CI mass spectrometry <1997RCM1825, 1997CCL629>. In spiro-crypta cyclophosphazene derivatives 129, the major decomposition pathway involved the initial cleavage of a P–Cl bond rather than cleavage of an exocyclic P–N bond as is normally seen for cyclophosphazenes <2004JST139>.

12.21.3.4 Electronic Spectroscopy, Circular Polarization, and Polarimetry Electron absorption spectra of phosphorus porphyrin derivatives 112 display a Soret band in the 415–432 nm region and two Q bands. Electron-donating axial ligands cause a redshift. The dialkyl compounds 112 (X ¼ alkyl) show hypercharacter even though they are high-valent phosphorus(V) compounds <2001IC5553>. Polarimetry experiments provided support for the configurational stability of the TRISPHAT anion 88 in solution <1997AGE608>. Circular dichroism techniques have been used to demonstrate the diastereoselective preparation of chiral-at-metal complexes with achiral ligands through asymmetric induction using the TRISPHAT anion 88 as a chiral auxillary <2004CEJ2548>. Circular dichroism has also been used to determine the absolute configuration of other metal complexes containing the TRISPHAT anion 88 <2001EJI1745, 2006JCD2058>. Homochiral ion pairing of [Fe(eilatin)3]2þ and 88 has been demonstrated using circular dichroism <2006CC850>.

12.21.3.5 Infrared Spectroscopy Vibrational circular dichroism (VCD) and IR spectra of 88 have been compared to VCD and IR spectra derived from DFT calculations; the vibrational properties of the anion are discussed in detail <2005CH1143>. Vibrational data have only occasionally been reported for novel compounds with a spiro phosphorus atom. Associated N–H and free N–H stretching absorptions have been reported for amino spirophosphoranes 75 <1996T2995>, 36, 45, 50, and 60 <1997IC2044, 2000POL63>, and 120 <2001RJC330>. Absorption bands in 1350–1370 cm1 region have been attributed to the P¼N stretch in spirophosphonium compounds 14 <1996RJC1418>. An intense peak at 757 cm1 assigned to the symmetric P–O–C stretch has been used to support the oxaphosphete structure of 67 <2001TL4417>.

12.21.4 Thermodynamic Aspects Variable-temperature NMR studies have been employed to determine the thermodynamic activation parameters for the Berry pseudorotation of 69 and 70 <1995TL2261, 1996JA12866, 1999PS561, 2006EJO2739>, and of diastereomers of 73 <1997TL4107>. The
G‡ for these processes are typically in the range 20–30 kcal mol1 at 298 K. Thermodynamic activation parameters have also been calculated for other ligand processes such as the cyclization of 125 <1996TL8409>, the 1, 2 intramolecular ligand shift of 113, 130, and 131 <1999IC1336>, and the intraconversion between pentacoordinate and hexacoordinate isomers of 110 <1997JA11434>. The apicophilic isomer 70 (R ¼ Bu) was estimated to be 12 kcal mol1 more stable than the anti-apicophilic isomer 69 (R ¼ Bu) <2006EJO218>.

Compounds containing a Spiro Phosphorus Atom

12.21.5 Reactivity of Fully Conjugated Rings There are no fully conjugated spirophosphorus compounds. Novel classes of spiroaromatic ring systems having a common phosphorus atom in which each ring can exhibit either Mo¨bius or Hu¨ckel aromaticity have been proposed, such as 132 and 133 <2002J(P2)1499>.

12.21.6 Reactivity of Nonconjugated Rings 12.21.6.1 Spirophosphonia Compounds Reaction of 2-(methylamino)ethanol with 16 (X ¼ O) results in 1, 4 Michael-type addition leading to a ring expansion from a five-membered ring to a nine-membered ring in the spirosphosphonium ylide 135. The amino group presumably attacks the -carbon, followed by the hydroxyl group attacking the phosphorus center and cleavage of the P–C bond. Trifluoroethanol adds across the PTN bond of 16 to give spirophosphorane 134 (Scheme 1) <2002CC40, 2004JOC1880, 2005JCD1847>. The spirocylcic phophinimine derived from an isothiocyanate reacts similarly with trifluoroethanol to give 134 (X ¼ S). Hydrolysis of the product during open air recrystallization resulted in ring opening and formation of the vinyl phosphonate 136 (Scheme 2) <2005JCD1847>.

Scheme 1

Scheme 2

1083

1084 Compounds containing a Spiro Phosphorus Atom Spirophosphonium ylide 17 undergoes a two-step addition process with diols: first the P–N bond is cleaved, followed by addition of the OH bond across the PTN double bond. Reaction with binaphthol stops after the first step to give 137, whereas catechol adds across the double bond to give 138 (Scheme 3) <2004JOC1880>.

Scheme 3

12.21.6.2 Spirophosphoranes Triquinphosphoranes 79 react with borane to give two diasteromeric adducts with different selectivity (Scheme 4). The diasteroselectivity is dependent on the nature and position of the substituent <1999OM915>.

Scheme 4

Tetraaryl derivatives 61 (R ¼ H) undergo double alkene extrusion to give two equivalents of the alkene. Alkene extrusion is not seen in the analogous trifluoromethyl derivatives. Introducing electron-withdrawing groups to the aryl substituents causes a reduction in the ease of alkene extrusion (Scheme 5) <1997PS379>. Heating a toluene solution of spirophosphorane azide 140 promotes N2 elimination followed by a Curtius-type rearrangement to give the spirophosphonium compound 141 which is in dynamic equilibrium with the dimer 142 (Scheme 6) <2004JOC1880>. In the hydrolysis of neutral tricyclic hexacoordinate spirophosphorane 143 with internal N!P dative bonds, the six-membered phosphorinane ring is retained during the first stage of hydrolysis. Five-, seven-, and eight-membered rings were preferentially hydrolysed (Equation 4) <1998POL3643>.

Compounds containing a Spiro Phosphorus Atom

Scheme 5

Scheme 6

ð4Þ

1085

1086 Compounds containing a Spiro Phosphorus Atom Addition of hexafluoroacetone to compound 30 leads to cleavage of the P–P bond and formation of spirocyclic 29, containing two four-membered rings (Equation 5) <1997ZFA1325>.

ð5Þ

12.21.6.3 Spiroperphosphoranides Spirophosphoranes 70 bearing an alkyl ester group react with aromatic or aliphatic aldhehydes after treatment with BuLi to give the thermodynamically less-stable (Z)-alkenes with high selectivity <1997JA5970, 2002CL170>. The high (Z)-selectivity is attributed to the addition of the aldehyde being the rate-determining step and the rate of the reverse, retro-aldol reaction being slow. Hexacoordinate 139 rather than the usual pentacoordinate oxaphosphetane intermediates were proposed, but not observed (Scheme 7). The feasibility of such intermediates is supported by the relatively stable hexacoordinate phosphoranides 94 <1997TL547, 1997TL551>. Preparation of all four diastereomers of -hydroxy-diphenylethyl spirophosphoranes 72 facilitated a subsequent mechanistic study on stereospecific alkene formation <1997TL7753>. Treatment of all four with sodium or potassium bases yielded alkenes with high stereoselectivity; however, two of the diastereomers gave rise to the retro-aldol products <2003T255>. In two cases, hexacoordinate species were identified by the upfield 31P chemical shift ( 112 ppm). It was noted that phosphoranes that ring-closed to form hexacoordinate tricyclic species 139 were the ones that did not undergo the retro-aldol reaction to produce aldehydes. The ring closure was disfavored for intermediates with steric repulsion between trifluoromethyl and phenyl groups.

Scheme 7

Thermolysis of tricyclic spirophosphoranide containing an oxaphosphetane ring 94 (R1 ¼ R2 ¼ CF3) yielded an alkene and the oxidophosphorane 144, whereas heating 94 (R1 ¼ R2 ¼ Ar) results in the elimination of benzophenone derivatives and the formation of 145 (Scheme 8) <1997TL551>. Thermolysis of 95 generates stilbene quantitatively after 4 days at 60  C (Equation 6) <2002JA13154>. The elimination of stilbene from the same oxaphosphetane ring in the apicophilic trans-O isomer occurs rapidly even at 40  C to give the same products <1997TL7753, 2003T255>.

Compounds containing a Spiro Phosphorus Atom

Scheme 8

ð6Þ

12.21.7 Reactivity of Substituents Attached to Ring Carbon The reactivity of substituents attached to a ring carbon atom has attracted very little attention and no new examples are reported here.

12.21.8 Reactivity of Substituents Attached to Ring Heteroatoms Including Spiro Phosphorus Addition of triethylamine to 146 results in loss of HCl and formation of 147 which slowly dimerizes to give bisspirophosphorane 32 (Scheme 9) <1996PS493>. Substitution of the chloride in spirophosphorane 53 (R ¼ Cl) with pyrazole or imidazole has been reported <2006NJC717>.

Scheme 9

1087

1088 Compounds containing a Spiro Phosphorus Atom Pentacoordinate spiro phosphorus centers have been used instead of phosphoryl groups to stabilize adjacent carbanions for use in the Wittig and Horner–Wadsworth–Emmons (HWE)-type reactions. For example, lithiation of spiroxyphosphorane 148 with LiHMDS at 78  C generates lithiophosphorane 149 <1996JA1549, 1996PS156>. 13 C NMR indicates that a highly delocalized, nearly planar carbanion is formed, but the stereochemistry of the enolate is undetermined. Reaction with benzaldehyde is presumed to proceed via trigonal bipyramid phosphoranes which gives a diastereomeric mixture of hexacoordinated oxyphosphoranes 150, identified by characteristic upfield shift in the 31P NMR ( 106 to 116 ppm). Rapid equilibriation to pentacoordinate phosphoranes 151, followed by the slow extrusion of the alkene, gives the final anionic phosphorane product and a mixture of (E)- and (Z)-alkenes. The stereochemistry of the carbon–carbon double bond formation can be influenced by variation of the reaction temperature after the addition of benzaldehyde. Under kinetic control at low temperature, the anti-addition product is favored and the thermodynamically less stable (Z)-alkene predominates (Scheme 10).

Scheme 10

Akiba subsequently reported a much improved (Z)-selectivity for cinnamic esters by treating spirophosphorane 70 (R ¼ Me) with t-BuOK, followed by addition of benzaldehyde <1997JA5970>. A strong counterion effect was observed at 0  C with potassium enolates giving a (Z:E ratio of 98:2 compared to a Z:E ratio of 72:28 with lithium enolates. The steric hindrance of the trifluoromethyl groups results in almost exclusive production of the antiintermediate. It also reduces the possibility of a retro-aldol reaction and hence prevents thermal equilibriation between anti- and syn-intermediates. Thus, the high (Z)-selectivity is attributed to the addition of the aldehyde being the rate-determining step and the rate of the reverse, retro-aldol reaction being slow. Hexacoordinate rather than the usual pentacoordinate oxaphosphetane intermediates were proposed in agreement with the mechanism proposed by Evans, who identified such intermediates by characteristic 31P chemical shifts <1996JA1549>. However, such intermediates were not observed for 70. In an attempt to observe related hexacoordinate spiroperphosphoranides, -hydroxyalkylphosphorane 152 was synthesized by deprotonation of 70 followed by addition of benzophenone. Deprotonation of 152 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in diglyme at 130  C gave 94 in quantitative yield, as evidenced by a 100 ppm upfield shift in the 31P NMR. The initial species was found to undergo stereomutation to form isomer 153. NMR analysis suggested that the rate-determining step was heterolytic cleavage of a P–O bond assisted by a potassium ion (Scheme 11) <1997TL547>. A hydrospirophosphorane 154 reacts with methylsulfide via a free radical mechanism (Equation 7) <2001JOC6181>. The success of the reaction is dependent on their being minimal steric congestion around the central phosphorus of the radical species that attacks the dimethyl sulfide. Phosphoranes carrying the SMe group have been prepared by treating the hydrophosphorane 70 (R ¼ H) with DBU, followed by elemental sulfur and methyl iodide (Equation 8)

Compounds containing a Spiro Phosphorus Atom

<1997TL4107>. The analogous methoxy phosphorane is accessible via treatment of 70 with DBU, then SO2Cl2 and an excess of methanol. In both cases, a mixture of exo- and endo-isomers is obtained <1997TL4107>. The nucleophilic substitution reactions of the SMe compounds with alkyllithium reagents resulted in inversion of configuration at the phosphorus center. The corresponding methoxy complexes however gave varying ratios of inversion and retention products dependent on the stereochemistry of the starting materials and the polarity of the solvent (Equation 9); Table 8). Retention of configuration results from nucleophile entering between an equatorial carbon atom and the equatorial oxygen, rather than between the two equatorial carbons, which would lead to inversion. It appears that there is an attractive interaction between the methoxy group and the nucleophile which guides the attack of the nucleophile. Such an attraction is less prevalent in tetrahydrofuran (THF), hence some inversion is seen.

Scheme 11

ð7Þ

ð8Þ

1089

1090 Compounds containing a Spiro Phosphorus Atom

ð9Þ

Table 8 Stereochemistry of nucleophilic substitution reaction X

Reactant ratio exo:endo

Solvent

R

Product ratio exo:endo

Configuration

SMe SMe SMe OMe OMe OMe OMe OMe

90:10 88:12 7:93 90:10 93:7 93:7 7:93 10:90

Et2O Et2O Et2O Et2O Hexane THF Et2O Et2O

Me n-Bu Me Me Me Me Me Bu

10:90 20:80 85:15 91:9 85:15 44:56 66:34 60:40

Inversion Inversion Inversion Retention Retention Inversion Inversion Inversion

The reaction of spiro hydrophosphorane 70 (R ¼ H) with 3 equiv of alkyllithium reagents, followed by addition of HCl, gave monocyclic hydrophosphorane 133 with the hydride in the apical position (Equation 10). Isomers with intramolecular hydrogen bonding and intermolecular bonding to a solvent molecule were separated and characterized by X-ray crystallography <1996TL8409>.

ð10Þ

Preparation of all four diastereomers of -hydroxydiphenylethyl spirophosphoranes 72 via deprotonation of hydrospirophosphoranes 70 (R ¼ H) with BuLi facilitated a subsequent mechanistic study on stereospecific alkene formation <1997TL7753, 2002CL170>. Three of the diasteromers could be formed by reacting 70 (R ¼ H) with BuLi, followed by treatment with cis or trans-stilbene oxide at room temperature (Scheme 12). Diastereomer 155 was most conveniently prepared by treatment of 70 (R ¼ Bn) with BuLi followed by benzoyl chloride, to give carbonyl compound 154 and then subsequent stereoselective reduction with LiBH4 (Scheme 13) <1997TL7753>. Interestingly, the O-cis-isomer 69 gives a rearranged product 156 after benzoylation (Scheme 14) <2002JA13154>. Treatment of all four diasteromers of 72 with sodium or potassium bases yielded stilbenes with high stereoselectivity (Scheme 15) <2003T255>. Two of the diastereomers gave rise to some retro-aldol products. In two cases, hexacoordinate species were identified by the upfield 31P chemical shift ( 112 ppm). It was noted that phosphoranes that ring-closed to form hexacoordinate tricyclic species were the ones that did not undergo the retro-aldol reaction to produce aldehydes. The ring closure was disfavored for intermediates with steric repulsion between trifluoromethyl and phenyl groups.

Compounds containing a Spiro Phosphorus Atom

Scheme 12

Scheme 13

Scheme 14

O-cis-Spirophosphoranes 69, which display anti-apicophilicty, exhibit enhanced reactivity toward nucleophiles compared to O-trans-spirophosphoranes 70; for example 69 produces hexacoordinate 157 on treatment with MeLi at 0  C while 70 is unreactive under the same conditions (Scheme 16). Compound 69 (R ¼ Bn) is more reactive toward bases than 70 (R ¼ Bn) with KHMDS deprotonating 69 (R ¼ Bn) in THF at 0  C but not 70 (R ¼ Bn). n-BuLi was sufficiently basic to deprotonate both 69 and 70 <2002JA13154>. Further differences are observed in the stability and stereochemistry of the brominated products formed between the reaction of the anion with BrCF2CF2Br. The effect of the bromide substituent in the O-cis-derivative is such that it accelerates pseudorotation to the O-trans-isomer (Scheme 17).

1091

1092 Compounds containing a Spiro Phosphorus Atom

Scheme 15

Scheme 16

Compounds containing a Spiro Phosphorus Atom

Scheme 17

Two equivalents of hydrospirophosphorane 158 add rapidly to diimines at room temperature to give alkyl bis(aminospirophosphoranes) 159 (Equation 11) <2002T5651>. Amphiphilic (-amino)phosphonic acids 160 in enantiopure form have been synthesized by reacting chiral spirophosphoranes 158 with long-chain prochiral aldimines and subsequent selective hydrolysis (Scheme 18) <2003CC1858>. Reaction of spirophosphorane 158 derived from hydroxyisovaleric acid was nearly instantaneous, while reactions of spirophosphorane 43 (R ¼ Et) derived from diethyltartrate were very slow, requiring up to 10 days.

ð11Þ

Scheme 18

Reaction of hydrophosphorane 38 with sulfur or selenium in the presence of a base produces sulfuro- and selenospirophosphoranes 161 (Equation 12) <2002PS1255>.

ð12Þ

1093

1094 Compounds containing a Spiro Phosphorus Atom Spirophosphoranes 79 and 162 undergo ring opening upon reaction with [Rh(CO)2Cl]2 and [PtCl2(COD)] to give 163 and 49, respectively (Scheme 19; Equation 13) <2000JOM148>.

Scheme 19

ð13Þ

Spirophosphorane 162 also undergoes ring opening upon treatment with [PtCl2(COD)] and [PdCl2(COD)] to give 164 (M ¼ Pd, Pt) (Equation 14) <1999ICA164>.

ð14Þ

Reaction of 165 with neutral nucleophiles such as aniline leads to disubstitution of the PCl2 group but with no further substitution. Sterically undemanding charged nucleophiles replace all the three chlorines (Scheme 20) <2004CEJ4915>.

Scheme 20

Compounds containing a Spiro Phosphorus Atom

12.21.9 Ring Syntheses 12.21.9.1 All Components Acyclic 12.21.9.1.1

Spirophosphonia compounds

There are no ring syntheses of spirophosphonia compounds starting from acyclic components to report.

12.21.9.1.2

Spirophosphoranes

Spirooxyphosphoranes 166 were obtained by the cyclodehydration of ortho-carboxyarylmethyl phosphine oxides under acidic conditions (Equation 15) to give 166 (X ¼ Y ¼ O) in which the oxygens occupy the axial positions. Related spirocyclic azoxyphosphoranes 166 (X ¼ NH, NMe) were synthesized from amidoarylmethyl phosphine oxides and trifluoracetic acid <1996PS241>.

ð15Þ

Dichloromethylphosphine reacts with 2 equiv of 4,4,4,-trifluorobutane-3-hydroxyl-1-phenylbutane-1-one to give the unstable trioxy spirophosphorane with a bridgehead phosphorus 77 (R ¼ Me) (Scheme 21) <1997JFC129>. Reaction of dichlorophenylphosphine with hexafluoropentane-2,4-dione gave a similar product 77 (R ¼ Ph) <1998HAC173>.

Scheme 21

Treatment of bis(-hydroxyalkyl)phosphine oxides with triphenylphosphine and a base yields spirophosphorane 61 possessing two 1,2-oxaphosphetane rings (Equation 16) <1997PS379, 1997AGE2500>. All diastereomers could be obtained. Oxidation of tri(o-tolyl)phosphine with potassium permanganate was used to generate spirophosphorane 74 (Equation 17) <2001IC6229>. Treatment of chloromethyl)dichlorophosphine with N,N9-bis(trimethylsilyl)dimethylurea yielded 30 (Equation 18) <1997ZFA1325>. Acylaminotetraoxyspirophosphoranes 167 (R ¼ H, Me, Pri, Bui, Bn) are conveniently synthesized by the treatment of EtOPCl2 with N,O-bis(trimethylsilyl)amino acids followed by addition of phenanthrenequinone (Equation 19) <1998S376>.

ð16Þ

1095

1096 Compounds containing a Spiro Phosphorus Atom

ð17Þ

ð18Þ

ð19Þ

Substitution of two chlorines in (1,2-benzenedioxy)trichlorophosphorane by N,O bis(trimethylsilyl)amino acids gives 34 (X ¼ Cl); further substitution of chlorine by phenol gives 34 (X ¼ OPh) (Scheme 22) <1998S855>. The reaction of P(NMe2)3 with 2-aminophenols generates aminophosphoranes 33 (R ¼ H, But) (Equation 20) <2000HAC11>.

Scheme 22

ð20Þ

Compounds containing a Spiro Phosphorus Atom

The norephedrine derivatives 168 and 169 yielded only one epimer of the spirophosphorane in each case, viz. 78 and 84, respectively (Equations 21 and 22). The selectivity is attributed to the methyl group - to the axial nitrogen favoring an exo-position <1997PS5, 1997RCB1154>. Spirocyclic tricyclophosphoranes 83 (X ¼ CH2, CO) were synthesized from P(NMe2)3 and N,N9-bis[2-hydroxyl)phenyl]ethylenediamine and N,N9-bis[2-hydroxyl)phenyl]oxamide <1997PS5>. The reaction of P(NMe2)3 with diaminodiols 170 in toluene under reflux gives bicyclic spirophosphoranes 79 after 30 min (Equation 23). Chiral diaminodiols 171 derived from cyclohexanediamine and diphenyl ethylene-1,2-diamine gave 172 (Equation 24) <1999OM915>.

ð21Þ

ð22Þ

ð23Þ

ð24Þ

Addition of glutaric acid to PCl3 affords spirophosphorane 173, which undergoes ring closure involving the exocyclic carboxylic acid to give a lactone structure 38 (Scheme 23) <2002PS1255>. Macrocyclic bis-spirophosphoranes 174 have been prepared by condensation of P(NMe2)3 with isopropylidenemannitols (Scheme 24) <2001PS177>.

Scheme 23

1097

1098 Compounds containing a Spiro Phosphorus Atom

Scheme 24

Spiro hydrophosphorane 175 is conveniently prepared by addition of 2 equiv of glycidol to PCl3 at low temperature (Equation 25) <1997PS173, 2000RJC708>. The formation of analogous bromethyl derivatives as by-products in the reaction of glycidol with bromotris(alkoxy)phosphoinium bromides has also been reported <1997RJC1204>.

ð25Þ

12.21.9.1.3

Spiroperphosphoranides

Addition of 3 equiv of tetrachlorocatechol to a toluene solution of phosphorus pentachloride followed by treatment with an amine base produces the hexacoordinated phosphorus anion 88 known as TRISPHAT (Equation 26) <1997AGE608>. Fluorinated TRISPHAT anions 90 have been synthesized using 1 equiv of 3-fluorocatechol or 4fluorocatechol <2005AGE5060>. C2-symmetric spirophosphoranide anions 87 (R ¼ Me, Et, Pri, But) containing a tartrate ligand have also been prepared in a one-pot process <2002HCA1364>. The chiral tartrate ligands impose some control on the configuration of the anions and diastereoselectivity is observed. In the preparation of BINPHAT anion 85, the chiral C2-symmetric BINOL ligand controls the configuration such that a diastereomeric ration of >39:1 is obtained. This represents the first example of complete predetermination of chirality of a phosphorus center in a hexacoordinate spirophosphoranide by a chiral ligand. The reaction proceeds via a three-step one-pot reaction (Scheme 25) <2000OL4185>.

ð26Þ

Compounds containing a Spiro Phosphorus Atom

Scheme 25

Only partial control of the phosphorus configuration is achieved by chiral hydrobenzoin ligands in the formation of HYPHAT anion 86 from P(NMe2)3, tetrachlorocatechol, and diarylethane-1,2-diol (Equation 27) <2002JOM392>. Although rapid precipitation of the anion gives the kinetic product in high diastereoselectivity (de 92%), when the product is dissolved epimerization occurs giving a reduced diastereoselectivity (de 50%). The diasteroselectivity is increased if ortho-bromo-substituents are introduced to the phenyl rings of the hydrobenzoin ligands. This is attributed to the ortho-subsituent increasing the steric interaction between the aryl groups and the terachlorocatecholate ligands.

ð27Þ

A range of bis(tetrachlorocatecholato)spirophosphoranides 91 and 92 have been prepared from diones <2002EJO3580>. Careful fine-tuning of the polarity of the solvent mixture was required for the precipitation of the dimethylammonium salts of the spirophosphoranides. A C1-symmetric spirophosphoranide 93 with three different bidentate ligands was also prepared. The synthesis required the addition of the dione to a phosphoramidite generated

1099

1100 Compounds containing a Spiro Phosphorus Atom in situ followed by addition of enantiopure diol. The dimethylammonium salt of 93 was isolated as the major product by selective precipitation from dichloromethane. The reaction of tropolone, bi(2-naphthol), and phosphorus trichloride affords the novel C2-symmetric hexacoordinated phosphorus cation 89 as a mixture of two diastereomers. Isolation of the major diastereomer was achieved by a chromatographic exchange of the chloride counterion with 88 (Equation 28) <2002OL2309>.

ð28Þ

Hexacoordinate spirocyclic phosphorus compounds have been prepared in which the spirocyclic system involves dative bonds from the dimethylamino-1-naphthyl ligand <1996JOM173, 1997PS181, 1999IC1336> for example 113 (Equation 29). Spirophosphoranide 122 was synthesized by deprotonation of the acid precursor 121 with triethylamine (Equation 30) <2001IC6229, 2002IC1645>.

ð29Þ

ð30Þ

12.21.9.2 From One Monocyclic Component 12.21.9.2.1

Spirophosphonia compounds

Tris-spiro compounds have been generated from hexachlorocyclotriphosphazene by substitution with dihydroxybypyridine derivatives (Equation 31) <1999IC5457>. Treatment of hexachlorocyclotriphosphazene with 2 equiv of biphenol or binaphthol yields only the meso-compounds 25 and 176. Enantiomerically pure cyclotriphosphazenes were generated from the (R)- or (S)-forms of binaphthol (Equation 32) <1999EJI1673>.

Compounds containing a Spiro Phosphorus Atom

ð31Þ

ð32Þ

Octachlorocyclotetraphoshazene 177 reacts with the sodium salt of 2,29-methylenebis(4,6-di-tert-butylphenol) to give the 2,2-spiro product 28. A similar substitiution product 27 is formed when 177 is reacted with 1 equiv of N,N9diisopropylpropane-1,3-diamine 178. Reaction of 177 with two equivalents of 178 gave the novel 2,2,6,6-dispiro derivative 179 (Scheme 26). Reaction of hexachlorocyclotriphosphazene with two equivalents of 178 gave the monospiro derivative 126 (X ¼ Cl) <1999JCD891>. The tetra-spiro cyclic cyclophosphazene 181 is the major product of the thermolysis of the azide 180 (Equation 33) <2003ICC394>.

Scheme 26

1101

1102 Compounds containing a Spiro Phosphorus Atom

ð33Þ

A range of bis- and tris-spirocyclic cyclotriphosphazenes 182–187 containing bi-2-napthoxy, 2,29-biphenoxy, 2,2dimethyl-1,3-propane diamino, and 2,2-dimethyl-1,3-propane dioxy ligands have been prepared from the appropriate diamines and diols <2004POL979>.

Compounds containing a Spiro Phosphorus Atom

Chiral spermine-bridged cyclotriphosphazenes 21 have been synthesized by the reaction of a gem-disubstituted cyclophosphazene 188 with spermine (Equation 34). The chiral products are also accessible by derivatizing a spermine-bridged cyclophosphazene <2002JCD365>.

ð34Þ

Treatment of spermine-bridged cyclophosphazene 189 with 1,3-propanediol gives a mixture of spiro and ansa derivatives. The formation of spiro forms is preferred; mono-, di-, tri-, and tetra-spiro forms, 190–193 were all isolated. A di-spiro, mono-ansa structure 194 was also isolated <2006POL953>. A similar preference for spiro derivatives over ansa derivatives was seen for the reaction of tetrafluorobutane-1,4-diol with hexachlorotriphosphazene. Again, a range of isomers 24, 195, 196, and 197 were isolated <2006POL963>. Cis and trans geometric isomers of di-spiro products 198–201 have been synthesized from the reaction of 3-amino-propanol or N-methylethanolamine with hexachlorocyclotriphosphazene <2004ICC657>. Spirane-bridged cyclotriphosphazenes 20 and 202 have been prepared by treatment of disubstituted tetrachlorocyclotriphosphazene with pentaerythritol <2004EJO1881>. When the reaction was repeated with the sodium derivative of pentaerythritol, the formation of the ansa ring was favored. Large quantities of the spiro–ansa derivative 203 were obtained <2006JCD1302>.

1103

1104 Compounds containing a Spiro Phosphorus Atom

A range of spiro and ansa isomers 204–207 were isolated from the reaction of 202 (X ¼ Cl) with 1,3-propanediol and sodium hydride (Equation 35) <2005EJI1042>. The monospiro monoansa spirane derivaties are meso-diastereomers. The formation of a spiro group is 4 times more likely than an ansa group. This preference is consistent with the spiro ring being in a six-membered stable chair form in contrast to an eight-membered strained ansa ring.

ð35Þ

Compounds containing a Spiro Phosphorus Atom

Condensation of hexachlorotriphoshazene and crown ethers offers a route to novel spiro-crypta-phosphazene derivatives 129 (n ¼ 1, 2) (Equation 36) <2004JST139>. The reaction is regioselective with no ansa-cryta and bino- isomers being produced. Diazaphospholes generated from the thermolysis of diazphospholenes react with diimines or benzil to give spiro compounds 14 <1996RJC1418>.

ð36Þ

Phosphorus(III) isocyanate and phosphorus(III) isothiocyanates 208 undergo 1,3-(P,C) dipolar cycloaddition with dimethyl acetylenedicarboxylate (DMAD) to give spirocyclic phosphinimines 16 (Equation 37) <2002CC40, 2005JCD1847>. The reaction of the thiocyanate with diethyl azodicarboxylate (DEAD) gives 209 as the major product and the triphosphorus compound 210 as a minor product (Equation 38). The yield of the latter can be increased by reducing the amount of DEAD used. A novel spirophosphonium compound 212 is obtained when DMAD is reacted with azide 211; the reaction involves two molecules of azide and one of DMAD (Equation 39) <2002CC40>. The isocyanate 208 (X ¼ O) reacts similarly with dialkylazocarboxylates (Equation 40) <2004JOC1880>.

ð37Þ

ð38Þ

1105

1106 Compounds containing a Spiro Phosphorus Atom

ð39Þ

ð40Þ

12.21.9.2.2

Spirophosphoranes

Reaction between ,"-diketone and 2,6-bis(trifluoroacetyl)-4-methylphenol gave the cycloaddition product 213 (Equation 41) <1997PS419>.

ð41Þ

Phospholine 214 dimerizes to give 215 on standing at 20  C for 30 days. Both 214 and 215 give spirophosphorane 216 on treatment with aminophenol. The mechanism is thought to involve addition of aminophenol to a phosphonimidate intermediate (Scheme 27) <2001RJC330>. Alkylation of thiophosphoramide 217 generates a range of cyclen(alkylthio)phosphoranes 218 (Equation 42) <1996T2995>. Treatment of a seleno-subsitituted phosphorane 219 containing a diazaphosphetidinone ring with bis(2-chloroethyl)amine hydrochloride and triethylamine gave the spirophosphorane 220 in 21% yield (Equation 43) <1995ZFA2001, 1997ZFA1325>. The oxidative addition of hexafluoroacetone to 221 gives 222 (X ¼ CH) in which chloromethane has been eliminated in a ring-closing step to give a product with a bridgehead phosphorus center (Scheme 28). Analogous products 223 were obtained by treatment of 221 (X ¼ N) with hexafluoroacetone (Scheme 29) <2000ZFA412>. The oxidative addition was found to be reversible. Treatment of the phosphoric ester 224 with triethylamine breaks the intramolecular hydrogen bonding in the solution structure and promotes cyclization to give spirophosphorane 43 (Equation 44) <2003PS2117>.

Compounds containing a Spiro Phosphorus Atom

Scheme 27

ð42Þ

ð43Þ

Scheme 28

1107

1108 Compounds containing a Spiro Phosphorus Atom

Scheme 29

ð44Þ

The macrocyclization of bis-hydrobicyclophosphoranes 225 with pentan-1,5-diols carrying different O, S, NMe substituents at the 3-position and polyethylene glycols gave a large range of ring bis(spirophosphoranes) 82 (Equation 45) <1996PS51>.

ð45Þ

Akiba and co-workers reported the first isolation of a spirophosphorane that exhibited reversed apicophilicity without employing steric constraints to block the formation of the normal configuration. Compounds 69 and 70 were formed by the thermal cyclization of 125 with the elimination of H2 (Equation 46) <1996JA12866>. Heating monocyclic hydrophosphoranes in donor solvents favors formation of anti-apicophilic spirophosphoranes 69 (R ¼ Me, n-Bu, and tert-Bu). Heating the same compounds in non-donor solvents results in the formation of the thermodynamically more stable apicophilic spirophosphoranes 70 in which the oxygens occupy the apical positions. <2006EJO218>. This method is not generally suitable for synthesizing phosphoranes with reversed apicophilicity as the elevated temperatures promote the isomerization to the more stable O-trans-isomer. A milder procedure was subsequently developed in which 70 (R ¼ H) was treated with BuLi to give the dianion and then oxidized in situ using suitable agents such as iodine, hydrogen peroxide, or metachloroperbenzoic acid (MCPBA) (Scheme 30) <1999PS561, 2001OL1873, 2002JA13154, 2006EJO2739>. This method produces O-cis-isomers 70 (R ¼ Me, Bu, But, aryl) exclusively at low temperatures and in high yields. It also allowed O-cis-phosphoranes bearing an aryl group to be isolated for the first time. In this case, a carbon occupies an axial position with one of the two oxygens occupying an equatorial position. The O-cis-spirophosphoranes were found to be much more reactive toward nucleophilic attack than the corresponding trans-isomers <2002PS1671>.

Compounds containing a Spiro Phosphorus Atom

ð46Þ

Scheme 30

A range of diastereomeric spirophosphoranes were synthesized from a Martin ligand 226 and a modified Martin ligand 227, where one trifluoromethyl group is replaced by a methyl group (Scheme 31) <2002JOM441>.

Scheme 31

The first spirophosphorane with an azaphosphetidine ring 63 was prepared from the intramolecular cyclization and dehydration of phosphane oxides with DEAD/PPh3 <1996AGE1096, 1996PS489>. Dissolution of 63 in [d8]-toluene led to some isomerization to the pseudorotamer 64, where the electronegative nitrogen occupies the equatorial position (Scheme 32). Such rotamers were previously unknown for the analogous oxaphosphetanes.

1109

1110 Compounds containing a Spiro Phosphorus Atom

Scheme 32

Oxaphosphetanes which display such reverse apicophilicity and have been assumed to be the intermediates in the Wittig reaction that give the alkene product were subsequently reported. In this case, a tertiary butyl group rather than a phenyl group was required to stabilize the anti-apicophilic isomer. Oxidation of 228 using BuLi followed by iodine gave a 1:1 mixture of 65 and 66 (Equation 47) <2002JA7674>. Isomer 65 could be crystallized out of solution by addition of hexane. When 65 was dissolved in anhydrous CDCl3, complete conversion to 66 occurred within minutes.

ð47Þ

Ribonucleosides such as uridine undergo an ester exchange reaction with oxyphosphorane 229 to give diasteromeric spiroxyphosphorane 39 in solution (Equation 48). The labile product was not isolated. Cytidine, guanosine, and adenosine analogues were also generated and characterized by NMR spectroscopy <1996PS257, 1997TL1615>.

ð48Þ

12.21.9.2.3

Spiroperphosphoranides

A series of tricyclic spiroperphosphoranides 231 (R ¼ Me) have been synthesized by the reaction of spirophosphoranes 230 with tetrachlorocatechol in the presence of NEt3. The same complexes could also be synthesized via addition of tetrachlorocatechol to spiroperphosporanides generated from the treatment of 230 with hexafluoropropan2-ol and triethylamine (Scheme 33) <2000JOC304>.

Compounds containing a Spiro Phosphorus Atom

Scheme 33

The reaction of azaphosphole 232 with 2 equiv of DEAD gives ths zwitterionic spiroperphosphoranide 233 in 37% yield (Equation 49) <2000S417>.

ð49Þ

12.21.9.3 By [4þ2] Cycloaddition to Phosphorus 12.21.9.3.1

Spirophosphoranes

[4þ2] Cycloaddition reactions of phosphines with diketones have continued to be exploited in the synthesis of fivecoordinate spirophosphoranes. A range of cyclic phosphites 234 undergo [4þ2] cycloaddition reactions with diisopropyl azodicarboxylate (DIAD) to give a mixture of two isomers of the spirophosphorane product 54 and 235, where the monodentate substituent occupies an apical or an equatorial site (Equation 50) <2002JOC6653>. Spirophosphoranes 58 were formed by the cycloaddition of cyclic phosphite 115 with O-tetrachloroquinone (Equation 51) <1995IC4525>. Spirophosphorane 57 was formed by similar reaction starting with 236 (Equation 52) <1996IC6552>. Related products 56 derived from 115 can be obtained by oxidation with benzil, instead of tetrachloro-1,2-benzoquinone <1996IC6552>. A range of spirophosphoranes 36, 44, 45, 50, 51, 52, 59, and 60 with an equatorial cyclohexylamino or methylamino group have been prepared by oxidative addition reaction using tetrachloro-1,2-benzoquinone or 9,10-phenanthraquinone and appropriate cyclic aminophosphites <1997IC2044, 2000POL63>. Subsequent syntheses of complexes 116 (X ¼ N(Me)Ph, N(Pri)2, NCS) and 117 (X ¼ NH2, NHPh, NHMe) demonstrated that with the sterically hindered eight-membered ring, axial–equatorial and equatorial–equatorial arrangements were equally feasible, for example, Equation (53) <1996JA9841, 1996IC6552, 1997IC2044, 2000JA964, 2002IC2356>.

1111

1112 Compounds containing a Spiro Phosphorus Atom

ð50Þ

ð51Þ

ð52Þ

ð53Þ

Compounds containing a Spiro Phosphorus Atom

Heptafluoro-4-(trifluoromethyl)-2,3-pentanedione undergoes cycloaddition with phosphorus isocyanate 237 to give a spirocyclic dioxaphospholene 35 (Equation 54) <1997PS419>.

ð54Þ

Oxidative addition of perfluorinated diketones to benzodiazophosphorinone 238 followed by a ring-closing N-alkylation step and subsequent elimination of chloroform produces tricyclic spirophosphoranes 80 (Equation 55). It was found that steric bulk at the N-3 substituent plays a key role in forcing the ring closure. In the case of the methyl derivative 239, N-alkylation does not occur and a bicyclic spirophosphorane 240 is isolated instead (Equation 56) <1997JFC109>. Amino-substituted 1,3,5,2-triazaphosphorinanediones 241 also react with perfluorinated diketones without ring closure, for example, the formation of 47 (Equation 57) <1996CB725>. The oxidative addition of tetrachloro-o-benzoquinone to the diazaphosphorinone 242 proceeds via a similar route giving the tricyclic spirophosphoranes 243 after abstraction of chloromethane (Equation 58) <1996S473>. Perfluorinated diketone has been added to 244 to give spirophosphorane 245 with a 1,3,2-dioxaphosphole ring (Equation 59) <2005RJC549>.

ð55Þ

ð56Þ

ð57Þ

ð58Þ

1113

1114 Compounds containing a Spiro Phosphorus Atom

ð59Þ

Phosphorus heterocycles 246 derived from hydroxyphenyl benzimidazole and aminophenyl benzimidazole undergo oxidative cycloaddition with 3,5-di-tert-butyl-1,2-benzoquinone to give a mixture of 247 and 248 (Equation 60) <2004HAC307, 2004HAC321>. Oxidative addition of ortho-chloranil to bis- and tetrakis-cyclodiphosphazene compounds gives bis- and tetrakis-spirophosphoranes, for example, 41 (Equation 61).

ð60Þ

ð61Þ

12.21.9.3.2

Spirophosphoranides

Cycloaddition of ortho-chloroanil and phenanthrenequinone to the appropriate cyclic phosphite 249 (X ¼ Cl) yields neutral hexacoordinate products 107 and 108 in which the sulfur is coordinated to the phosphorus center, for example, Equation (62) <1997JA1317>. Further derivatives 107 (X ¼ NMe2, NHTol) and 108 (X ¼ NMe2, NHBn) are accessible by substitution of 107 and 108 (X ¼ Cl) with amines <1997JA1317, 1998IC3747>. Reaction of catechol and 3-fluorocatechol with 249 gives similar compounds, for example, 109 <1997IC5730>.

Compounds containing a Spiro Phosphorus Atom

ð62Þ

The sulfonyl group containing cyclic phosphine 250 was treated with ortho-chloroanil or catechol to prepare 110 and 251, respectively (Scheme 34) <1997IC2578, 1997JA11434>. In compound 251, the sulfonyl group is not coordinated to the phosphorus. This can be attributed to the electron-withdrawing behavior of the phenoxy group and the four chloro substituents on the catechol group increasing the electrophilicity of the phosphorus, hence favoring the Lewis base action of the sulfonyl group.

Scheme 34

The hexacoordinate spirophosphorane 105 has been synthesized from the [4þ2] cycloaddition reaction between 252 and DIAD (Equation 63) <2004JOC1880>. Hexacoordination is also seen in the chloro derivative 114; however, in this case, the chloro substituent is positioned cis to the coordinated sulfur rather than the trans-position occupied by the phenyl group in 105 <2006NJC717>.

ð63Þ

1115

1116 Compounds containing a Spiro Phosphorus Atom

12.21.9.4 By [2þ2] Cycloaddition to Phosphorus 12.21.9.4.1

Spirophosphoranes

Keglevich reported the first examples of [2þ2] cycloaddition involving a PTO group and an alkyne. The reactivity of the PTO group is a consequence of the electron-donating P-aryl substituents employed. A series of spirocyclic oxaphosphetes including 62–67, the unsaturated derivatives of the oxaphosphetane intermediates in the Wittig reaction, were synthesized from DMAD and phosphorus heterocycles, for example, Equations (64) and (65) <1999CC1423, 2000T4823, 2001TL4417>. It is of interest that while 4-chloro-5-methyl-1-aryl-1,2-dihydrophosphinine oxide 253 underwent a [2þ2] cycloaddition with DMAD, the isomeric 4-chloro-3-methyl-1-aryl-1,2-dihydrophosphinine oxide reacted with DMAD according to a [4þ2] cycloaddition, albeit slowly. The difference in reactivity is attributed to the steric hindrance of the 2,4,6-trimethylphenyl group suppressing Diels–Alder reactivity in the 3-methyl derivative <2001J(P1)1062>. Spirocyclic oxaphosphetanes 68 can be formed by the [2þ2] cycloaddition of imino-oxaphospholenes 254 and hexafluoroacetone (Equation 66) <2002HAC97>. The first azaphosphetine containing spirophosphorane 256 was isolated as the [2þ2] cycloaddition product from the reaction of iminophosphorane 255 and an alkyne (Equation 67) <2000TL5237, 2001CC2096>.

ð64Þ

ð65Þ

ð66Þ

ð67Þ

12.21.9.4.2

Spiroperphosphoranides

Exposure of anion 257 to air at 0  C gave the tricyclic spiroperphosphoranide 98, which represents the first example of a dioxaphosphirane, a species containing a three-membered O–P–O ring (Equation 68) <1999JA6958>.

Compounds containing a Spiro Phosphorus Atom

ð68Þ

12.21.9.5 By ring modification 12.21.9.5.1

Spirophosphonia

There are no ring modification reactions of spirophosphonia to report.

12.21.9.5.2

Spirophosphoranes

Treatment of 30 with hexafluoroacetone results in a ring contraction to give compound 29 (Equation 69) <1997ZFA1325>.

ð69Þ

12.21.9.6 Other Methods 12.21.9.6.1

Spirophosphoranes

Electrophilic addition to spiro phosphenium cations 258 provides a route to spirophosphoranes. However, only very active electrophiles are suitable, for example, benzenesulfonyl azide which on reflux in acetonitrile with 258 yields 259 (Equation 70) <1998RJC530>.

ð70Þ

12.21.9.6.2

Spiroperphosphoranide

Addition of phosphinomethyl spirophosphorane 260 to isocyanates and azides presumaby generates anionic nitrogen intermediates that cyclize with the phosphorane to give spirophosphoranides 96, 97, and 261 (Scheme 35) <1996PS493>. Addition of chlorine to spirophosphenium cation 262 generates the six-coordinate 263, which can be converted to the more stable tetrachlorocatechol derivative 264 by addition of bis(trimethylsiloxy)tetrachlorobenzene (Scheme 36) <1998RJC530>.

1117

1118 Compounds containing a Spiro Phosphorus Atom

Scheme 35

Scheme 36

Tricyclic spirophosphoranides 94 containing an oxaphosphetane ring unsubstituted at the carbon  to phosphorus have been observed in solution below 40  C. These were prepared by deprotonation of apicophilic spirophosphoranes 265 (X ¼ R1R2C(OH)CH2 in the presence of a crown ether (Equation 71) <1997TL547, 1997TL551>. At higher temperatures, alkene elimination occurs. Treatment of the anti-apicophilic spirophosphorane 266 with a phenyl group at the -position under the same conditions generates a stable six-coordinate tricyclic spirophosphoranide 95 (Equation 72) <2002JA13154>.

ð71Þ

Compounds containing a Spiro Phosphorus Atom

ð72Þ

A range of hexacoordinate phosphorus(V) porphyrins 111 and 112 (X ¼ Cl, R, OH, OR, NEt2) have been prepared by inserting PCl3 into octaethylporphyrin 267 in the presence of 2,6-dimethylpyridine (Equation 73). Further derivatization with alcohols and amines to give 268–271 was reported (Scheme 37) <1995JA8287, 2001IC5553>.

Scheme 37

1119

1120 Compounds containing a Spiro Phosphorus Atom

ð73Þ

Addition of pyridine-2-thiol to hexachlorocyclotriphoshazene in the presence of triethylamine gave the bissubstituted cyclotriphosphazene 99. The pyridine thiolate group is bonded to the phosphorus in a bidentate fashion giving a hexacoordinate product <1996IC6899>. A neutral hexacoordinate spirophosphorane 115 is prepared by substituting two phenoxide groups with biphenol (Equation 74) <2004JOC1880>. The lithium salt of tris(oxalato)phosphate 272 has been isolated from the reaction of oxalic acid with PCl5 followed by addition of lithium hydride (Equation 75) <2004CEJ2451>.

ð74Þ

ð75Þ

A range of neutral tricyclic hexacoordinate spirophosphoranes with internal N ! P dative coordination have been synthesized by addition of diols to monocyclic phosphites <1996JA9841>. For example, reaction of 273 with 1 equiv of 2,29-biphenol at 60  C in the presence of N-chlorodiisopropylamine gave the tricyclic derivative 100. Treatment of 273 with 2 equiv gave 101 as an additional product in 30% yield (Scheme 38). This derivative must arise from the exchange of the six-membered phosphorinane ring by a seven-membered phosphepin ring. Perhaps more surprising is that a similar reorganization occurs when 274 is reacted with 8-hydoxyquinoline even though no 2,29-biphenol is added (Equation 76). It was suggested that the aromatic substituents on the phosphepin ring increase the Lewis acidity of the phosphorus center, thereby increasing the strength of the N ! P dative bond in the resulting complex.

Compounds containing a Spiro Phosphorus Atom

Scheme 38

ð76Þ

12.21.10 Critical Comparison of Routes to Compounds Containing a Spirocyclic Phosphorus Atom The initial synthesis and resolution of 88 was performed as a one-step procedure with the resolving agent added to the reaction mixture after addition of PCl5 <1997AGE608>. An improved two-step procedure enabled the scale-up of the reaction from a 100 mg scale to a 40 g scale <1998TL4825, 2004JOC8521>.

12.21.11 Important Compounds and Applications 12.21.11.1 Nonmedical Applications The D3-symmetric TRISPHAT anion 88, tris(tetrachlorobenzenediolato)phosphate, is chiral and configurationally stable. It can be resolved by association with chiral ammonium salts such as cinchonidine <1997AGE608, 2004JOC8521>. TRISPHAT 88 displays high selectivity for cinchonidine and does not associate with the related diasteromer cinchonine <1998TL4825>. The selective ion pairing behavior of TRISPHAT has been exploited in

1121

1122 Compounds containing a Spiro Phosphorus Atom simple ion exchange chromatography and the purification of cationic species such as triarycarbenium and monomethine cations <1998TL567> and others <2002OL3939>. The strong ion pairing results in poor affinity for polar chromatographic phases. Anion 88 has been used for asymmetric induction on cationic metal complexes <1998AGE2379, 2001EJI1745, 2002AGE2317, 2003CC2014, 2006CC850>, enantioselective extraction of a tris(diimine) ruthenium complexes <2000AGE3695>, synthesis of enantiomers of (bipyridyl)ruthenium complexes <2003EJI499>, resolution of dinuclear triple helicates by asymmetric extraction/precipitation <2000CEJ4297>, diastereoselective homochiral self assembly <2001EJI201>, self-assembly of a fluorescent pseudorotoxane <2006EJO105>, enantiodifferentiation of triphenylphosphonium salts <2003TL2467>, and stereoselective precipitation <2003IC4810, 2004CEJ2548>. It has found its greatest use however as a chiral shift reagent in NMR spectroscopy <1997CC2285>. It has been applied to a wide range of cationic ruthenium <2001JOM388, 2002OM4385>, rhodium and iridium <2002MI257>, manganese <2001OM4107>, and cobalt <2001OM1904> complexes. It has even been successful for enantiodifferentiation of neutral chromium arene complexes <2000OM3997, 2003CC658>. The ion pairing of 88 with chiral copper complexes allows enantiodifferentiation by NMR spectroscopy, which enabled the kinetics of racemization to be determined <2003IC255, 2006JCD2058>. A comparative study of the enatiodifferentiation by NMR spectroscopy of a chiral ruthenium complex using 88 and Eu(tfc)3 revealed that 88 was superior due to less signal broadening and a better signal-to-noise ratio <2003NJC748>. C2-symmetric spirophosphoranides 85 <2000OL4185> and HYPHAT <2002JOM392> have displayed improved chiral shift properties for organic cations such as metacholine <2002OL1351, 2002TL423>. The hexacoordinate phosphate(V) cation 89 has been shown to be an efficient chiral shift reagent for chiral phosphate and borate anions <2002OL2309>. The ion pairing of racemic helicene derivatives with enatiomerically pure 85 enabled identification by NMR spectroscopy of the P and M enantiomers of chiral helicene cations <2003AGE3162>. The applications of spirophsophanides have been reviewed in more detail elsewhere <2003CSR373, 2005OBC15>.

12.21.11.2 Compounds of Medical Interest Compounds containing a spirocyclic phosphorus atom have attracted very little medical interest; no new examples are reported here.

12.21.12 Further Developments Further spirophosphonia compounds derived from hexachlorocyclotriphosphazene and octachlorocyclotetraphosphazene have been reported <2006IC8755, 2007IC2575, 2007JST172>. Other recent developments include the experimental determination of nN!* P-O interaction energy of O-equatorial C-apical spirophosphoranes bearing an amino group <2006IC7269> and the synthesis of a nitrogen-containing derivative of the TRISPHAT anion which allows the stereocontrol of chiral ligands bound to metal centers <2007OM2141>.

References N. V. Timosheva, A. Chandrasekaran, T. K. Prakasha, R. O. Day, and R. R. Holmes, Inorg. Chem., 1995, 34, 4525. Y. Yamamoto, R. Nadano, M. Itagaki, and K.-y. Akiba, J. Am. Chem. Soc., 1995, 117, 8287. D. Houalla, L. Moureau, S. Skouta, and M. R. Mazie´res, Phosphorus, Sulfur Silicon Relat. Elem., 1995, 103, 199. S. Kojima, M. Nakamoto, K. Kajiyama, and K.-y. Akiba, Tetrahedron Lett., 1995, 36, 2261. V. A. Pinchuk, C. Muller, A. Fischer, H. Tho¨nnessen, P. G. Jones, R. Schmutzler, L. N. Markovsky, Y. G. Shermolovich, and A. M. Pinchuk, Z. Anorg. Allg. Chem., 1995, 621, 2001. 1996AGE1096 T. Kawashima, T. Soda, and R. Okazaki, Angew. Chem., Int. Ed. Engl., 1996, 35, 1096. 1996CB725 A. Kadyrov, I. Neda, T. Kaukorat, R. Sonneburg, A. Fischer, P. G. Jones, and R. Schmutzler, Chem. Ber., 1996, 129, 725. 1996CHEC-II(8)1135 J. C. Tebby; in ‘Comprehensive Heterocyclic Chemistry’, A. R. Katritzky, C. W. Rees, and E. F. V. Scriven, Eds.; Pergamon, Oxford, 1996, Vol. 8, p. 1135. 1996IC6552 N. V. Timosheva, A. Chandrasekaran, T. K. Prakasha, R. O. Day, and R. R. Holmes, Inorg. Chem., 1996, 35, 6552. 1996IC6899 O. S. Jung, S. H. Park, Y. A. Lee, Y. H. Cho, K. M. Kim, S. Lee, K. Chae, and Y. S. Chon, Inorg. Chem., 1996, 35, 6899. 1996JA1549 M. L. Bojin, S. Barkallah, and S. A. Evans, Jr., J. Am. Chem. Soc., 1996, 118, 1549. 1996JA9841 M. A. Said, M. Pulm, R. Herbst-Irmer, and K. C. Kumara Swamy, J. Am. Chem. Soc., 1996, 118, 9841. 1996JA12866 S. Kojima, K. Kajiyama, M. Nakamoto, and K. Akiba, J. Am. Chem. Soc., 1996, 118, 12866. 1996JOM173 M. Chauhan, C. Chuit, R. J. Corriu, C. Reye´, J. P. Declerq, and A. Dubourg, J. Organomet. Chem., 1996, 510, 173. 1996PS156 S. Barkallah, M. L. Bojin, and S. A. Evans, Jr., Phosphorus, Sulfur Silicon Relat. Elem., 1996, 109–110, 156. 1996PS241 O. Nir, M. Fridkin, and Y. Segall, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 109–110, 241. 1996PS489 T. Kawashima, T. Soda, K. Kato, and R. Okazaki, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 109–110, 489. 1995IC4525 1995JA8287 1995PS199 1995TL2261 1995ZFA2001

Compounds containing a Spiro Phosphorus Atom

1996PS493 1996PS51 1996PS257 1996RJC1418 1996S473 1996T2995 1996TL8409 1997AGE608 1997AGE2500 1997CB819 1997CC2285 1997IC2044 1997IC2578 1997IC5730 1997JA1317 1997JA5970 1997JA11434 1997JFC129 1997JFC109 1997RCB1154 1997CCL629 1997PS5 1997PS181 1997PS379 1997PS419 1997PS173 1997RCM1825 1997RJC1204 1997TL547 1997TL551 1997TL1615 1997TL4107 1997TL7753 1997ZFA1325 1998AGE1098 1998AGE2379 1998HAC173 1998IC3747 1998JA6848 1998POL3643 1998RJC530 1998S376 1998S855 1998TL567 1998TL4825 1999CC1423 1999EJI1673 1999JA6958 1999JCD891 1999JFC223 1999IC1093 1999IC1336 1999IC5457 1999ICA164 1999OM915 1999PAC531 1999PS561 1999RJC333 2000AGE3695 2000CEJ4297 2000HAC11

I. G. Shevchenko, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 109–110, 493. D. Houalla and L. Moureau, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 114, 51. X. Chen, N.-J. Zhang, Y. Ma, and Y.-F. Zhao, Phosphorus, Sulfur Silicon Relat. Elem., 1996, 118, 257. A. M. Kibardin, T. V. Gryaznova, A. D. Pudovik, and V. A. Naumov, Russ. J. Gen. Chem., 1996, 66, 1418. I. Neda, C. Melnicky, A. Vollbrecht, and R. Schmutzler, Synthesis, 1996, 473. N. Oget, F. Chuburu, J. J. Yaouanc, and H. Handel, Tetrahedron, 1996, 52, 2995. K. Kajiyama, S. Kojima, and K.-y. Akiba, Tetrahedron Lett., 1996, 37, 8409. J. Lacour, C. Ginglinger, C. Grivet, and G. Bernadinelli, Angew. Chem., Int. Ed. Engl., 1997, 36, 608. T. Kawashima, R. Okazaki, and R. Okazaki, Angew. Chem., Int. Ed. Engl., 1997, 36, 2500. S. Volbrecht, A. Volbrecht, J. Jeske, P. G. Jones, R. Schmutzler, and W. W. Du Mont, Chem. Ber. Recueil, 1997, 130, 819. J. Lacour, C. Ginginger, F. Favarger, and S. Torche-Haldimann, Chem. Commun., 1997, 2285. M. A. Said, M. Pulm, R. Herbst-Irmer, and K. C. Kumara Swamy, Inorg. Chem., 1997, 36, 2044. A. Chandrasekaran, R. O. Day, and R. R. Holmes, Inorg. Chem., 1997, 36, 2578. P. Sood, A. Chandrasekaran, T. K. Prakasha, R. O. Day, and R. R. Holmes, Inorg. Chem., 1997, 36, 5730. D. Sherlock, A. Chandrasekaran, R. O. Day, and R. R. Holmes, J. Am. Chem. Soc., 1997, 119, 1317. S. Kojima, R. Takagi, and K.-y. Akiba, J. Am. Chem. Soc., 1997, 119, 5970. A. Chandrasekaran, R. O. Day, and R. R. Holmes, J. Am. Chem. Soc., 1997, 119, 11434. V. G. Ratner, E. Lork, K. I. Pashkevich, and G. V. Ro¨schenthaler, J. Fluorine Chem., 1997, 85, 129. I. Neda, C. Muller, and R. Schmutzler, J. Fluorine Chem., 1997, 86, 109. I. S. Mikhel, K. N. Gavrilov, D. V. Lechki, and A. I. Rebrov, Russ. Chem. Bull., 1997, 46, 1154. Q. Wang, H. Y. Lu, X. Chen, and Y. Zhao, Chin. Chem. Lett., 1997, 8, 629. M. Tlahuextl, F. J. Martı´nez-Martı´nez, M. Rosales-Hoz, and R. Contreras, Phosphorus, Sulfur Silicon Relat. Elem., 1997, 123, 5. F. Carre´, M. Chauhan, C. Chuit, R. J. Corriu, and C. Reye´, Phosphorus, Sulfur Silicon Relat. Elem., 1997, 123, 181. T. Kawashima, R. Okazaki, and R. Okazaki, Phosphorus, Sulfur Silicon Relat. Elem., 1997, 124–125, 379. M. Go¨rg, U. Dieckbreder, R.-M. Schoth, A. A. Kadyrov, and G.-V. Ro¨schenthaler, Phosphorus, Sulfur Silicon Relat. Elem., 1997, 124–125, 419. A. A. Bredikhin, S. A. Lazarev, Z. A. Bredikhina, and V. A. Al’Fonsov, Phosphorus, Sulfur Silicon Relat. Elem., 1997, 131, 173. H. Fu, Z. Li, Y. Zhao, D. Guo, H. Xiao, J. Wang, and Y. Wu, Rapid Commun. Mass Spectrom., 1997, 11, 1825. V. F. Mironov, A. A. Bredikhin, Z. A. bredikhina, V. G. Novikova, and I. V. Knovalova, Russ. J. Gen. Chem. (Engl. Trans.), 1997, 67, 1204. S. Kojima and K.-y. Akiba, Tetrahedron Lett., 1997, 38, 547. T. Kawashima, K. Watanabe, and R. Okazaki, Tetrahedron Lett., 1997, 38, 551. X. Chen, N.-J. Zhang, Y.-M. Li, Y. Jiang, X. Zhang, and Y.-F. Zhao, Tetrahedron Lett., 1997, 38, 1615. S. Kojima, M. Nakamoto, K. Yamazaki, and K.-y. Akiba, Tetrahedron Lett., 1997, 38, 4107. S. Kojima, K. Kawaguchi, and K.-y. Akiba, Tetrahedron Lett., 1997, 38, 7753. I. Neda, V. A. Pinchuk, A. Thonnessen, L. Ernst, P. G. Jones, and R. Schmutzler, Z. Anorg. Allg. Chem., 1997, 623, 1325. H. Luo, R. McDonald, and R. G. Cavell, Angew. Chem., Int. Ed. Engl., 1998, 37, 1098. J. Lacour, J. J. Jodry, C. Ginglinger, and S. Torche-Haldimann, Angew. Chem., Int. Ed. Engl., 1998, 37, 2379. G. Bekiaris and G. V. Roschenthaler, Heteroatom Chem., 1998, 9, 173. P. Sood, A. Chandrasekaran, R. O. Day, and R. R. Holmes, Inorg. Chem., 1998, 37, 3747. T. Kawashima, K. Kato, and R. Okazaki, J. Am. Chem. Soc., 1998, 120, 6848. K. C. K. Swamy, M. A. Said, S. Kumaraswamy, R. Herbst-Irmer, and M. Pu¨lm, Polyhedron, 1998, 17, 3643. S. E. Pipko, Y. V. Balitskii, A. N. Chernega, and A. D. Sinitsa, Russ. J. Gen. Chem., 1998, 68, 530. N.-J. Zhang, H.-Y. Lu, X. Chen, and Y.-F. Zhao, Synthesis, 1998, 376. H. Fu, G.-Z. Tu, Z.-L. Li, and Y.-F. Zhao, Synthesis, 1998, 855. J. Lacour, S. Barche´chath, J. J. Jodry, and C. Ginglinger, Tetrahedron Lett., 1998, 39, 567. J. Lacour, C. Ginglinger, and F. Favarger, Tetrahedron Lett., 1998, 39, 4825. G. Keglevich, H. Forintos, A. Szo¨llo¨sy, and L. To¨ke, Chem. Commun., 1999, 1423. I. Dez, J. Levalois-Mitjaville, H. Gru¨tzmacher, V. Gramlich, and R. de Jaeger, Eur. J. Inorg. Chem., 1999, 1673. M. Nakamoto and K.-y. Akiba, J. Am. Chem. Soc., 1999, 121, 6958. S. Kumaraswamy, M. Vijjulatha, C. Muthiah, K. C. Kumara Swamy, and U. Engelhardt, J. Chem. Soc., Dalton Trans., 1999, 891. O. D. Gupta, R. L. Kirchmeier, and J. M. Shreeve, J. Fluorine Chem., 1999, 97, 223. N. Thirupathi, S. S. Krishamurthy, and M. Nethaji, Inorg. Chem., 1999, 38, 1093. M. Chauhan, C. Chuit, A. Fruchier, and C. Reye´, Inorg. Chem., 1999, 38, 1336. O.-S. Jung, Y. T. Kim, Y.-A. Lee, Y. J. Kim, and H. K. Chae, Inorg. Chem., 1999, 38, 5457. A. V. Korostylev, O. G. Bondarev, K. A. Lyssenko, A. Yu Kovalevsky, P. V. Petrovskii, G. V. Tcherkaev, I. S. Mikhel, V. A. Davankov, and K. N. Gavrilov, Inorg. Chim. Acta, 1999, 295, 164. C. Marchi, F. Fotiadu, and G. Buono, Organometallics, 1999, 18, 915. G. P. Moss, Pure Appl. Chem., 1999, 71, 531. K.-y. Akiba, K. Kajiyama, M. Yoshimune, M. Nakamoto, and S. Kojima, Phosphorus, Sulfur Silicon Relat. Elem., 1999, 144– 146, 561. A. A. Preschenko, M. V. Livantsov, D. G. Pol’shchikov, E. V. Grigor’ev, S. N. Nikolaev, and D. N. Kustrya, Russ. J. Gen. Chem. (Engl. Transl.), 1999, 69, 333. J. Lacour, C. Goujon-Ginglinger, S. Torche-Haldimann, and J. J. Jodry, Angew. Chem., Int. Ed. Engl., 2003, 39, 3695. J. J. Jodry and J. Lacour, Chem. Eur. J., 2000, 6, 4297. J. Herna´ndez-Dı´az, R. Contreras, and B. Wrackmeyer, Heteroatom Chem., 2000, 11, 11.

1123

1124 Compounds containing a Spiro Phosphorus Atom

2000IC1338 2000JA964 2000JA12447 2000JOC304 2000JOM148 2000OL4185 2000OM3997 2000POL63 2000POL2667 2000RJC708 2000S417 2000T4823 2000TL5237 2000ZFA412 2001CC2096 2001EJI201 2001EJI1745 2001IC5553 2001IC6229 2001J(P1)1062 2001JOC6181 2001JOM388 2001OL1873 2001OM1904 2001OM4107 2001PS177 2001RJC330 2001TL4417 2002AGE2317 2002CC40 2002CL170 2002CJC1501 2002EJO3580 2002HAC97 2002HAC390 2002JA6126 2002JA7674 2002JA13154 2002JCD365 2002J(P2)1499 2002JOC6653 2002JOM392 2002JOM441 2002IC1645 2002IC2356 2002MI257 2002HCA1364 2002OL1351 2002OL2309 2002OL3939 2002OM4385 2002POL1155 2002PS1255 2002PS1671 2002T5651 2002TL423 2003AGE3162 2003CC658

A. Chandrasekaran, N. T. Timosheva, R. O. Day, and R. R. Holmes, Inorg. Chem., 2000, 39, 1338. S. Kumaraswamy, C. Muthiah, and K. C. Kumara Swamy, J. Am. Chem. Soc., 2000, 122, 964. D. B. Davies, T. A. Clayton, R. E. Eaton, R. A. Shaw, A. Egan, M. B. Hursthouse, G. D. Sykara, I. Porwolik-Czomperlik, M. Siwy, and K. Brandt, J. Am. Chem. Soc., 2000, 122, 12447. A. Skowronska, J. Kowara, R. Kaminski, G. Bujacz, and M. W. Wieczorek, J. Org. Chem., 2000, 65, 304. K. N. Gavrilov, A. V. Korostylev, A. I. Polosukhin, O. G. Bondarev, K. A. Lyssenko, A. Yu. Kovalevsky, and V. A. Davankov, J. Organomet. Chem., 2000, 613, 148. J. Lacour, A. Londez, C. Goujon-Ginglinger, V. Buss, and G. Bernardinelli, Org. Lett., 2000, 2, 4185. H. Ratni, J. J. Jodry, J. Lacour, and E. P. Ku¨ndig, Organometallics, 2000, 19, 3997. C. Muthiah, M. S. Said, M. Pu¨lm, R. Herbst-Irmer, and K. C. Kumara Swamy, Polyhedron, 2000, 19, 63. T. Glowiak, W. K. Rybak, and A. Skarzynska, Polyhedron, 2000, 19, 2667. A. A. Bredikhin, S. N. Iazarev, Y. Y. Efremov, D. R. Sharafutadinova, and Z. A. Bredikhina, Russ. J. Gen. Chem. (Engl. Transl.), 2000, 70, 708. C. Peters, F. Tabellion, M. Schro¨der, U. Bergstra¨ßer, F. Preuss, and M. Regitz, Synthesis, 2000, 3, 417. G. Keglevich, H. Forintos, G. M. Keseru¨, L. Hegedu¨s, and L. To¨ke, Tetrahedron, 2000, 56, 4823. N. Kano, X. J. Hua, S. Kawa, and T. Kawashima, Tetrahedron Lett., 2000, 41, 5237. R. Sonnenburg, I. Neda, H. Tho¨nnessen, P. G. Jones, and R. Schmutzler, Z. Anorg. Allg. Chem., 2000, 626, 412. N. Kano, A. Kikuchi, and T. Kawashima, Chem. Commun., 2001, 2096. O. Maury, J. Lacour, and H. Le Bozec, Eur. J. Inorg. Chem., 2001, 201. M. Brissard, M. Gruselle, B. Male´zieux, R. Thouvenot, C. Guyard-Duhayon, and O. Convert, Eur. J. Inorg. Chem., 2001, 1745. K.-y. Akiba, R. Nadano, W. Satoh, Y. Yamamoto, S. Nagase, Z. Ou, X. Tan, and K. M. Kadish, Inorg. Chem., 2001, 40, 5553. A. Chandrasekaran, R. O. Day, and R. R. Holmes, Inorg. Chem., 2001, 40, 6229. G. Keglevich, A. Vasko´, A. Dobo´, K. Luda´nyi, and L. To¨ke, J. Chem. Soc., Perkin Trans. 1, 2001, 1062. M. Garrossian, W. G. Bentrude, and G.-V. Ro¨schenthaler, J. Org. Chem., 2001, 66, 6181. D. Monchand, J. Lacour, C. Coudret, and S. Fraysse, J. Organomet. Chem., 2001, 624, 388. K. Kajiyama, M. Yoshimune, M. Nakamoto, S. Matsukawa, S. Kojima, and K.-y. Akiba, Org. Lett., 2001, 3, 1873. H. Amouri, R. Thouvenot, M. Gruselle, B. Malezieux, and J. Vaissermann, Organometallics, 2001, 20, 1904. J. Giner Planas, D. Prim, E. Rose, F. Rose-Munch, D. Monchaud, and J. Lacour, Organometallics, 2001, 20, 4107. A. Munoz and A. Rochale, Phosphorus, Sulfur Silicon Relat. Elem., 2001, 174, 177. S. A. Terent’eva, M. A. Pudovik, A. T. Gubaidullin, I. A. Litvinov, and A. N. Pudovik, Russ. J. Gen. Chem. (Engl. Transl.), 2001, 71, 330. G. Keglevich, T. Ko¨rtve´lyesi, H. Forintos, A. Tama´s, K. Luda´nyi, V. Izvekov, and L. To¨ke, Tetrahedron Lett., 2001, 42, 4417. D. Monchaud, J. J. Jodry, D. Pomeranc, V. Heitz, J.-C. Chambron, J.-P. Sauvage, and J. Lacour, Angew. Chem., Int. Ed., 2002, 41, 2317. S. Kumaraswamy, P. Kommana, N. Satish Kumar, and K. C. Kumara Swamy, Chem. Commun., 2002, 40. S. Kojima, K. Kawaguchi, S. Matsukawa, K. Uchida, and K.-y. Akiba, Chem. Lett., 2002, 170. T. M. Barclay, R. G. Hicks, A. S. Ichimura, and G. W. Patenaude, Can. J. Chem., 2002, 80, 1501. J. Lacour, S. Constant, and V. Hebbe, Eur. J. Org. Chem., 2002, 3580. D. V. Sevenard, E. Lork, K. I. Pashkevich, and G.-V. Ro¨schenthaler, Heteroatom Chem., 2002, 97. K.-y. Akiba, S. Matsukawa, K. Kajiyama, M. Nakamoto, S. Kojima, and Y. Yamamoto, Heteroatom Chem., 2002, 390. U. Monkowius, N. W. Mitzel, A. Schier, and H. Schmidbaur, J. Am. Chem. Soc., 2002, 124, 6126. S. Kojima, M. Sugino, S. Matsukawa, M. Nakamoto, and K.-y. Akiba, J. Am. Chem. Soc., 2002, 124, 7674. S. Matsukawa, S. Kojima, K. Kajiyama, Y. Yamamoto, K.-y. Akiba, S. Re, and S. Nagase, J. Am. Chem. Soc., 2002, 124, 13154. S. J. Coles, D. B. Davies, R. J. Eaton, M. B. Hursthouse, A. Kilic, T. Mayer, R. A. Shaw, and G. Yenilmez, J. Chem. Soc., Dalton Trans., 2002, 365. H. S. Rzepa and K. R. Taylor, J. Chem. Soc., Perkin Trans. 2, 2002, 1499. N. S. Kumar, P. Kommana, J. J. Vittal, and K. C. Kumara Swamy, J. Org. Chem., 2002, 67, 6653. J. Lacour and A. Londez, J. Organomet. Chem., 2002, 643–644, 392. M. Nakamoto, S. Kojima, S. Matsukawa, Y. Yamamoto, and K.-y. Akiba, J. Organomet. Chem., 2002, 643–644, 441. A. Chandrasekaran, R. O. Day, and R. R. Holmes, Inorg. Chem., 2002, 41, 1645. P. Kommana, S. Kumaraswamy, J. J. Vittal, and K. C. Kumara Swamy, Inorg. Chem., 2002, 41, 2356. H. Amouri, R. Thouvenot, and M. Gruselle, C. R. Chim., 2002, 5, 257. J. Lacour, A. Londez, D.-H. Tran, V. Desvergnes-Breuil, S. Constant, and G. Bernardinelli, Helv. Chim. Acta, 2002, 85, 1364. J. Lacour, L. Vial, and C. Herse, Org. Lett., 2002, 4, 1351. J. Lacour, L. Vial, and G. Benardinelli, Org. Lett., 2002, 4, 2309. L. Vial and J. Lacour, Org. Lett., 2002, 4, 3939. J. G. Planas, D. Prim, F. Rose-Munch, and E. Rose, Organometallics, 2002, 21, 4385. S. Kumaraswamy and K. C. Kumara Swamy, Polyhedron, 2002, 21, 1155. A. Munoz, H. Gornitzka, and A. Rochal, Phosphorus, Sulfur Silicon Relat. Elem., 2002, 177, 1255. K.-y. Akiba, S. Matsukawa, T. Adachi, Y. Yamamoto, S. Re, and S. Nagase, Phosphorus, Sulfur Silicon Relat. Elem., 2002, 177, 1671. K. Vercruysse-Moreira, C. De´jugnat, and G. Etemad-Moghadam, Tetrahedron, 2002, 58, 5651. C. Pascquini, V. Desvergnes-Breuil, J. J. Jodry, A. Dalla Cort, and J. Lacour, Tetrahedron Lett., 2002, 43, 423. C. Herse, D. Bas, F. C. Krebs, T. Bu¨rgi, J. Weber, T. Weslowski, B. W. Laursen, and J. Lacour, Angew. Chem., Int. Ed. Engl., 2003, 42, 3162. A. Berger, J.-P. Djukic, M. Pfeffer, A. De Cian, N. Kyritsakas-Gruber, J. Lacour, and L. Vial, Chem. Commun., 2003, 658.

Compounds containing a Spiro Phosphorus Atom

2003CC1858 2003CC2014 2003CSR373 2003EJI499 2003IC255 2003IC4810 2003JA4943 2003JST35 2003NJC748 2003ICC394 2003POL843 2003PS2117 2003T255 2003TL2467 2004AXB739 2004CEJ2451 2004CEJ2548 2004CEJ4915 2004CJC1119 2004HAC307 2004HAC321 2004EJO1881 2004ICC657 2004ICC842 2004JST139 2004JOC1880 2004JOC8521 2004OL145 2004POL979 2005AGE5060 2005ARK102 2005CH1143 2005EJI1042 2005JCD1847 2005OBC15 2005RJC549 2006ACR324 2006CC850 2006EJO105 2006EJO218 2006EJO2739 2006IC7269 2006IC8755 2006JCD1302 2006JCD2058 2006NJC717 2006POL953 2006POL963 2007IC2575 2007JST172 2007OM2141

C. De´jugnat, G. Etemad-Moghadam, and I. Rico-Lattes, Chem. Commun., 2003, 1858. C. Perollier, S. Constant, J. J. Jodry, G. Bernardinelli, and J. Lacour, Chem. Commun., 2003, 2014. J. Lacour and V. Hebbe-Viton, Chem. Soc. Rev., 2003, 32, 373. R. Caspar, H. Amouri, M. Gruselle, C. Cordier, B. Malezieux, R. Duval, and H. Leveque, Eur. J. Inorg. Chem., 2003, 499. V. Desvergnes-Breuil, V. Hebbe-Viton, C. Dietrich-Buchecker, J.-P. Sauvage, and J. Lacour, Inorg. Chem., 2003, 42, 255. M. Chavarot, S. Me´nage, O. Hamelin, F. Charanay, J. Pe´caut, and M. Fontecave, Inorg. Chem., 2003, 42, 4810. S. Bes¸li, S. J. Coles, D. B. Davies, R. J. Eaton, M. B. Hursthouse, A. Kilic¸, R. A. Shaw, G. Yenilmez, C¸iftc¸i, and S. Yes¸ilot, J. Am. Chem. Soc., 2004, 125, 4943. J. Kanetti, S. M. Bakalova, and M. T. Nguyen, J. Mol. Struct., 2003, 633, 35. G. Bruylants, C. Bresson, A. Boisdenghien, F. Pierard, A. Kirsch-De Mesmaeker, J. Lacour, and K. Bartik, New. J. Chem., 2003, 27, 748. P. Kommana, S. Kumaraswamy, and K. C. Kumara Swamy, Inorg. Chem. Commun., 2003, 6, 394. P. Kommana, J. J. Vittal, and K. C. Kumara Swamy, Polyhedron, 2003, 22, 843. D. G. Boyer, M.-T. Boisdon, A. Rochal, and A. Munoz, Phosphorus, Sulfur Silicon Relat. Elem., 2003, 178, 2117. S. Kojima, K. Kawaguchi, S. Matsukawa, and K.-y. Akiba, Tetrahedron, 2003, 59, 255. V. Hebbe, A. Iondez, C. Goujon-Ginglinger, F. Meyer, J. Uziel, S. Juge´, and J. Lacour, Tetrahedron Lett., 2003, 44, 2467. S. Coles, D. B. Davies, M. B. Hursthouse, A. Kilic¸, T. A. Mayer, R. A. Shaw, G. Yenilmez, and C¸iftc¸i,, Acta Crystallogr. Sect. B, 2004, 60, 739. U. Wietelman, W. Bonrath, T. Netscher, H. No¨th, J-C. Pantiz, and M. Wohlfahrt-Mehrens, Chem. Eur. J., 2004, 10, 2451. O. Hamelin, J. Pecaut, and M. Fontecave, Chem. Eur. J., 2004, 10, 2548. S. Bes¸li, S. J. Coles, D. B. Davies, R. J. Eaton, M. B. Hursthouse, H. Ibis¸oglu, A. Kilic¸, and R. A. Shaw, Chem. Eur. J., 2004, 10, 4915. R. G. Hicks, Can. J. Chem., 2004, 82, 1119. J. Herna´ndez-Diaz, A. Flores-Parra, and R. Contreras, Heteroatom. Chem., 2004, 15, 307. J. Herna´ndez-Diaz, A. Flores-Parra, and R. Contreras, Heteroatom. Chem., 2004, 15, 321. S. J. Coles, D. B. Davies, R. J. Eaton, M. B. Hursthouse, A. Kilic¸, R. A. Shaw, and A. Uslu, Eur. J. Org. Chem., 2004, 1881. S. J. Coles, D. B. Davies, R. J. Eaton, M. B. Hursthouse, A. Kilic¸, R. A. Shaw, A. Uslu, and S. Yesilot, Inorg. Chem. Commun., 2004, 7, 657. S. Bes¸li, S. J. Coles, D. B. Davies, R. J. Eaton, M. B. Hursthouse, A. Kilic¸, R. A. Shaw, S. Sahin, A. Uslu, and S. Yesilot, Inorg. Chem. Commun., 2004, 7, 842. S. Bilge, Z. Kilic¸, N. Caylak, and T. Ho¨kelek, J. Mol. Struct., 2004, 707, 139. N. S. Kumar, K. P. Kumar, K. V. P. Pavan Kumar, P. Kommana, J. J. Vittal, and K. C. Kumara Swamy, J. Org. Chem., 2004, 69, 1880. F. Favarger, C. Goujon-Ginglinger, D. Monchaiud, and J. Lacour, J. Org. Chem., 2004, 69, 8521. P. Komman, N. Satish Kumar, J. J. Vittal, E. G. Jayasree, E. D. Jemmis, and K. C. Kumara Swamy, Org. Lett., 2004, 6, 145. N. S. Kumar and K. C. Kumara Swamy, Polyhedron, 2004, 23, 979. R. Frantz, A. Pinto, S. Constant, G. Bernardinelli, and J. Lacour, Angew. Chem., Int. Ed. Engl., 2005, 44, 5060. W. M. Abdou, M. A. I. Salem, and A. A. Sediek, ARKIVOC, 2005, 102. D. Bas, T. Bu¨rgl, J. Lacour, J. Vachon, and J. Weber, Chirality, 2005, 17, 143. A. Uslu, S. J. Coles, D. B. Davies, R. J. Eaton, M. B. Hursthouse, A. Kilic¸, and R. A. Shaw, Eur. J. Inorg. Chem., 2005, 1042. S. Kumaraswamy, K. S. Kumar, N. Satish Kumar, and K. C. Kumara Swamy, J. Chem. Soc., Dalton Trans., 2005, 1847. J. Lacour and R. Frantz, Org. Biomol. Chem., 2005, 3, 15. I. V. Konovalova, V. F. Mironov, G. A. Ivkova, E. R. Zagidullina, A. T. Gubaidullin, I. A. Litvinov, and M. A. Kurykin, Russ. J. Gen. Chem. (Engl. Transl.), 2005, 75, 549. K. C. Kumara Swamy and N. S. Kumar, Acc. Chem. Res., 2006, 39, 324. S. Bergman, R. Frantz, D. Gut, M. Kol, and J. Lacour, Chem. Commun., 2006, 850. M. Clement-Le´on, C. Pasquini, V. Hebbe-Viton, J. Lacour, A. Dalla Cort, and A. Credi, Eur. J. Org. Chem., 2006, 105. S. Kojima, K. Kajiyama, M. Nakamoto, S. Matsukawa, and K.-y. Akiba, Eur. J. Org. Chem., 2006, 218. K. Kajiyama, M. Yoshimune, S. Kojima, and K.-y. Akiba, Eur. J. Org. Chem., 2006, 2739. T. Adachi, S. Matsukawa, M. Nakamoto, K. Kajiyama, S. Kojima, Y. Yamamoto, K.-Y. Akiba, S. Re, and S. Nagase, Inorg. Chem., 2006, 45, 7269. S. Bilge, S¸ . Demiririz, A. Okumus¸, Z. Kilic¸, B. Tercan, T. Ho¨kelek, and O. Bu¨yu¨kgu¨ngo¨r, Inorg. Chem., 2007, 46, 8755. S. J. Coles, D. B. Davies, R. J. Eaton, M. B. Hursthouse, A. Kilic, R. A. Shaw, and A. Uslu, J. Chem. Soc., Dalton Trans., 2006, 1302. V. Hebbe-Viton, V. Desvergnes, J. J. Jodry, C. Dietrich-Buchecker, J.-P. Sauvage, and J. Lacour, J. Chem. Soc., Dalton Trans., 2006, 2058. K. V. P. Kumae, N. S. Kumar, and K. C. Kumara Swamy, New J. Chem., 2006, 30, 717. S. J. Coles, D. B. Davies, R. J. Eaton, A. Kilic¸, R. A. Shaw, and G. Yenilmez C¸iftc¸i, Polyhedron, 2006, 25, 953. S. Bes¸li, S. J. Coles, D. B. Davies, R. J. Eaton, A. Kilic¸, and R. A. Shaw, Polyhedron, 2006, 25, 963. E. W. Ainscough, A. M. Brodie, A. B. Chaplin, A. Derwahl, J. A. Harrison, and C. A. Otter, Inorg. Chem., 2007, 46, 2575. N. Asmafiliz, E. Ilter, M. Is¸iklan, Z. Kilic¸, B. Tercan, N. C¸aylak, T. Ho¨kelek, and O. Bu¨yu¨kgu¨ngo¨r, J. Mol. Struct., 2007, 832, 172. S. Constant, R. Frantz, J. Mu¨ller, G. Bernardinelli, and J. Lacour, Organometallics, 2007, 26, 2141.

1125

1126 Compounds containing a Spiro Phosphorus Atom Biographical Sketch

Neil Williams studied at the University of Southampton, where he obtained a first class B.Sc. (Hons.) degree in chemistry in 1989 and his Ph.D. in 1993, under the supervision of Professor J. Evans. He then spent two years at the National Institute of Materials and Chemical Research in Japan as a Royal Society/Japanese STA Fellow, working in the laboratory of Professor M. Tanaka. In 1995, he returned to the United Kingdom with a Royal Society Return Fellowship, which he took up at the University of Sussex, working with Professor M. Lappert, FRS. After a further period of postdoctoral work at the University of East Anglia and a temporary lecturership at the University of Central Lancashire, he took up a lectureship at Kingston University in 1999. He is now a principal lecturer in the School of Pharmacy and Chemistry at Kingston University. His research interests lie in the field of ligand synthesis and homogeneous catalysis.