Compounds containing a Spiro Phosphorus Atom

8.41 Compounds containing a Spiro Phosphorus Atom JOHN C. TEBBY Staffordshire University, Stoke-on-Trent, UK 8.41.1 INTRODUCTION

1136

8.41.2 THEORETICAL METHODS

1137

8.41.3 EXPERIMENTAL STRUCTURAL METHODS

1143

8.41.3.1 X-ray diffraction 8.41.3.2 Magnetic Resonance 8.41.3.2.1 NMRSpectroscopy 8.41.3.2.2 Electron spin resonance spectrometry 8.41.3.3 Mass Spectrometry 8.41.3.4 Electronic Spectroscopy, Circular Polarization, and Polarimetry 8.41.3.5 Vibrational Spectroscopy

1143 1147 WAI 1149 1149 1149 1150

8.41.4

THERMODYNAMIC ASPECTS

1150

8.41.5

REACTIVITY OF FULLY CONJUGATED RINGS

1150

8.41.6

REACTIVITY OF NONCONJUGATED RINGS

1150

8.41.6.1 8.41.6.2 8.41.6.3

Spirophosphonium Salts and Ylides Spirophosphoranes Spiroperphosphoranides

1150 1151 1152

8.41.7

REACTIVITY OF SUBSTITUENTS ATTACHED TO RING CARBON

1153

8.41.8

REACTIVITY OF SUBSTITUENTS ATTACHED TO RING HETEROATOMS INCLUDING SPIRO PHOSPHORUS

1154

8.41.9

RING SYNTHESES

1155

8.41.9.1 All Components Acyclic 8.41.9.1.1 Spirophosphonia compounds 8.41.9.1.2 Spirophosphoranes 8.41.9.1.3 Perphosphoranides 8.41.9.2 From One Monocyclic Component 8.41.9.2.1 Spirophosphonia compounds 8.41.9.2.2 Spirophosphoranes 8.41.9.2.3 Spiroperphosphoranides 8.41.9.3 By 2 + 4 Cyclouddition to Phosphorus 8.41.9.3.1 Spirophosphonia compounds 8.41.9.3.2 Spirophosphoranes 8.41.9.4 By 2 + 2 Cycloaddition to Phosphorus 8.41.9.4.1 Spirophosphoranes 8.41.9.5 By Ring Modification 8.41.9.5.1 Spirophosphonia compounds 8.41.9.5.2 Spirophosphoranes 8.41.9.6 Other Methods 8.41.9.6.1 Spirophosphoranes 8.41.9.6.2 Spiroperphosphoranides

1155 1155 1156 1157 1157 1157 1159 1163 1163 1163 1164 1164 1164 1165 1165 1165 1166 1166 1166

1135

Compounds containing a Spiro Phosphorus Atom

1136

1167 1167 1168

8.41.10 IMPORTANT COMPOUNDS AND APPLICATIONS 8.41.10.1 Nonmedical Applications 8.41.10.2 Compounds of Medical Interest

8.41.1

INTRODUCTION

Compounds which have four coordinate phosphorus at the spiro position are analagous to the corresponding quaternary ammonium compounds in that they may be salts, for example phosphoniaspiro(m,n)alkanes (1), or mesoionic, for example an ylide. However, phosphorus may also be five coordinate, for example spirophosphorane (2), and indeed these compounds have attracted the major attention of phosphorus chemists. There are also a number of six coordinate spiro phosphorus compounds which may also be a salt, for example anion (3), or mesoionic. The six coordinate state permits the formation of a third ring, for example anion (4). In these valence expanded states, the compounds are stabilized by small rings (usually five membered rings), and by the presence of electronegative atoms or groups bound to phosphorus, either as part of a ring(s) and/or as the noncyclic group(s). There also exists an example of a tetraaza analogue of a phosphonium fenestrane (5) <8UAl28i). A further consequence of the five and six coordinate states is the possibility of a new spiro situation where the spiro phosphorus atom is also a bridgehead atom, for example phosphorane (6). Y (CH 2 ) n

(CH 2 )

Y (CH2)M

(CH 2 ) m

(CH2)W

(CH 2 ) n

Z (3)

(2)

(1)

P-

(CH 2 ) n

(CH 2 ) (CH 2 ) n

(CH 2 )

(CH 2 ) m

(CH 2 )

(CH 2 ) (4)

(6)

As with the nitrogen analogues there are no fully conjugated compounds, but there are many examples of spiro phosphorus atoms which are part of five- and six-membered rings possessing six p electrons, for example the cyclotriphosphazene (7). However in these coordination states the phosphorus atom is not able to transmit the potential conjugation and the compounds show no evidence of aromaticity. Organophosphorus chemistry is renowned for its nomenclature problems. One striking fundamental nomenclature problem relates to the six coordinate compounds R6P~ which have been called phosphates and causing confusion with four coordinate (ortho)-phosphates. However IUPAC rules indicate that the six coordinate compounds R 6 P" should be named "perphosphoranides" the four coordinate phosphorus anions R4P~ being named as phosphoramides as usual. There are many compounds which have a variety of heterocyclic atoms and structural features which makes the formal IUPAC system unduly complex. As a consequence in this review the more common ring systems have been abbreviated to a set of three letters to represent the atoms and groups making up the ring apart from the central phosphorus atom, for example the glycol group OCH2CH2O is abbreviated to Glc. A list of abbreviations is given below (see Figure 1). x

X I

P=N

N X

P-N

Y

X (7)

The range of cyclic systems is shown in the tables below (Tables 1-16), m and n representing the sizes of the spiro rings. The four, five, and six coordinate compounds will normally be reviewed in

Compounds containing a Spiro Phosphorus Atom

H

R

R N H

N

O

N N H

Ami

Amc

N H

Amo

Bip

Bid

O O

O

Dme

Don

Dop

O

O

O

O

N H Eph

N H

O

Eta

Glc

Cat

F3C N H

\ Nox

Oam

Me Me

Pmp

Ph

O

Hyc

O

F3C

O

Pfc

Pic

O

Me Me

N H Pda

O

Pfe

H N

O

Dpe

Gls O

FiC

Ph

O

F3C

O-N

1137

O

Cl

Pnc

Tic

Ch = O, S, Se (Chalcogenide) E = CO2R

Figure 1 Structural abbreviations used in Chapter 8.41

this sequence. There are very few alicyclic compounds which have phosphorus as the only hetero atom. There are more examples of benzo derivatives, but the vast majority of compounds incorporate a number of additional hetero atoms within the ring systems. The five coordinate spirophosphoranes have played an important role with respect to understanding the stereochemistry of four coordinate phosphorus reactions which proceed via phosphorane intermediates. Variable temperature NMR studies have established the apicophilicities of a wide range of groups (i.e. relative preferences of a series of groups to occupy an apical position rather than an equatorial position of a trigonal bipyramidal (t.b.p.) conformation of a phosphorane). The spiro ring system has been used to stabilize transient reaction intermediates of acyclic compounds, for example hydrolysis intermediates such as hydroxyphosphoranes.

8.41.2 THEORETICAL METHODS The stabilizing influence on the hypervalent state of phosphorus produced when phosphorus is incorporated into small rings is very well established and is especially effective in the spiro compounds

Compounds containing a Spiro Phosphorus Atom

1138

Table 1 Phosphoniaspiro compounds with P-bound atoms = C4.

x-

X

(10)

(9)

// A //

\

x-

Me.O Me

X

4 4 4 4 4 5 5 5 5

4 4 4 4 4 5 5 5 5

(13)

(12)

(U)

n

N-H

Me

O Me

m

H-N

N N

Ref.

Compound 5-phosphoniaspiro(4,4)nonane triiodide (1) 5-phosphonia(b,e)dibenzospiro(4,4)nonane (8) 5-phosphonia(a,c,d,f)tetrabenzospiro(4,4)nonane (9; R 5-phosphonia(a,c,d,f)tetrabenzospiro(4,4)nonane (9; R (10) 6-phosphoniaspiro(5,5)undecane bromide (1) 6-phosphoniaspiro(5,5)undecane ylide (11) urea (12) dibenzophosphorin (13)

68ZOB331 73JHC395 69JOC1130 73RTC1308 72CC404 80ZN(B)990 81CB3161 81PS207 75JOC766

H) Me)

Table 2 Phosphoniaspiro compounds with P-bound atoms = C2XY. CF3SO3

PC12

(15)

(14)

m

n

XY

4 4 4

4 5 5

o2 N2 o2

Compound benzodioxaphospholan (14) cyclotriphosphazene (15) (16)

SbCl6" (16)

Ref. 78JA7434 90JCS(D)2303 88ZAAC(561)49

covered here. Extended Hiickel MO calculations indicated that the small rings lowered the occupation of the phosphorus 3d orbitals and favored nucleophilic attack at phosphono leading to t.b.p. phosphoranes <69JA12OO>. Possible mechanisms for the permutational isomerism of five coordinate phosphoranes have been explored <74CC15>. The Berry pseudorotation mechanism <75CPL(30)276> involving t.b.p. intermediates, which deform via square pyramidal (s.p.) geometries where the two

Compounds containing a Spiro Phosphorus Atom

1139

Table 3 Phosphoniaspiro compounds with four P-bound nitrogen atoms. Me |

Me

NN

N\

Me Me

Me R

N

N

i

i

N'

N.

N i

I

Me

/

(17)

N"

i

Me Me

n

P-bound

3 3 3 3 4 4 4 4 5 5

3 3 4 5 4 4 5 5 5 5

N4 N4 N4 N4 N4 N4 N4 N4 N4 N4

P=N Ph 2

R

/

Me R

(18)

m

N

P N

N

Ph

H N

P-N

R

*

Y

N'

j

Me

N-

N P Ph2

N

(20)

(19)

Ref.

Compound (17; Y = Z = CO) (17; Y = Me 2 Si, Z = P(NR)NHR) (18) (17; Y = N H , Z = Me 2 Si) (19; Y = N = CMe) (19; Y = Q H 4 ) (7; Y = N M e , Z = [CH2]2) (7; Y = N M e , Z = Q H 4 ) (7; Y = N M e , Z = PCl 2 NMePCl 2 ) cyclotriphosphazene (20)

87JGU2143 87CB1183 74JCS(D)2153 77MI 841-03 86TL2971 91TL501 77CB3231 72JGU1490 77CB3231 75CB1454

Table 4 Phosphoniaspiro compounds with P-bound oxygen or sulfur atoms. HSO,

O

N

/V\

o o

CN /—Ph \

X

Ph CN

P I

i

m

n

P-bound

4 4 4 4 4 4 4 5 5 5 5 5

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

co 3 NO 3 N2O2 s4 N2O2 N2O2 N 2 O?

N2O2 S4 s4 N2O2 N2O2

N

(23)

N

(24)

N

Me

Y2 P-N

x

P\ 7

(22)

(21)

Ph

X Y

R O

N-P Y2 (25)

Compound (21) phosphazene (22) (23; X = O, Y = CMe = CMe) (24; R = [CH2]2) (7; Y = O, Z = [CH2]2) (7; Y = O, Z = [C 6 H 4 ) (23; X = O, Y = [CH J 3 ) (7; Y = O, Z = 1,8-dinaphthyl) (24; R = [CH2]3) (24; R = Q H 4 ) (7; Y = O, Z = Bid) (25; R = CH 2 CMe 2 CH 2 , Y = Cl)

Ref. 84PS(21)249 82JGU189 84TL5521 83ZN(B)1046 76ZAAC(426)275 76JA5120 76T2039 71IC1643 83ZN(B)1046 73CC144 76JA5120 91PS(55)59

apical bonds join two of the equatorial bonds—the remaining equatorial bond (the pivot) being transformed into the apical bond of the s.p. structure, remains the most favored mechanism <77JA3318>, although a turnstile mechanism <74T37l> based on NMR studies of (83) has been explored.

Compounds containing a Spiro Phosphorus Atom

1140

Table 5 Four coordinate compounds with two or more phosphoniaspiro centers.

O

O

Me i

R

Me

i

R RR

I

N ii

N \ / N\ / N\ +,PN + / P N / PXF 2 N N N I

i

Me

R

C12P

N

I

Me

2 F~ (28)

(26)

Cl2

CloP

HN^ ^N N N

I

P-bound

3 3 5 5 5 6 6

3 5 5 5 7 7 7

N4 C2N2 N2O2 N4 N2O2 N4 N2O2

,PC12

N /

NH

(30)

(29) n

11

N

HN

m

N

II

R

"N

/

Ref.

Compound (26) diphosphorin (27) (28) (29; R = (CH 2 ) 3 ) (25); R = Bip, Y 2 = Cat) (30) (25); R = Bip, Y 2 = O Q H 4 Q H 4 O )

86MI 841-01 93TL3107 75ICA(14)L40 89JST( 196)221 76JA5120 91PS(57)111 71IC1643

Table 6 Four coordinate spirophosphoranides R4P .

m

n

P-bound

4 4

4 4

C2O2 N4

Compound (31; Y = Me) Tme 2 P-

Ref. 78JA7434 94CCR53

Molecular mechanics calculations have been extended from four coordinate phosphoryl compounds to five coordinate phosphoranes by adding a term which measures the effects of electron pair repulsions, modified by the ligand electronegativity, and taking into account the t.b.p. and s.p. conformational possibilities <77JA546l). These studies were extended to calculations of the relative energies of t.b.p. and s.p. conformations <75JA5379>. It was concluded that the s.p. conformation is stabilized relative to the t.b.p. conformation when the phosphorus atom was part of an unsaturated

1141

Compounds containing a Spiro Phosphorus Atom Table 7 Five coordinate spirophosphoranes with P-bound atoms = C5 R1

R

P-R

R (33)

(32)

m

n

P-bound

4 4 4 4 4 4

4 4 4 4 4 4

Q C5 C5 c5 c5 c5

Ref.

Compound (2; Y = Me) (32) (33; R1 = H, R2 = CH=CMe 2 , 2-furyl, 2-thienyl) (33; R1 = H, R2 = Bun, C=CBu n ) (33; R1 = Me, R2 = Ph, 2-Pr) (34; proposed intermediate)

72AG(E)722 72CC404 70JCS(C)1425 70LA(742)163 74JA5398 83TL5831

Table 8 Five coordinate spirophosphoranes with P-bound atoms = C4X.

R3 (35) m

n

X

3 4 4 4

4 4 4 5

O H O O

(36) n = 2, 3 Compound

Wittig intermediate (35) (33; R1 = R2 = H) (36; n = 2) (36; n = 3)

Ref. 90JA3905 69CB528 79CB501 79CB501

ring and when the phosphorus was bound to highly electronegative atoms; that the t.b.p. conformation was destabilized by additional ring strain (3-4 kcal mol" 1 for the dioxaphospholenes) produced by the need for the different bond length requirements of the t.b.p. conformation and that the s.p. conformation also accommodated four membered rings better than the t.b.p. conformation. A method for the calculation of the barriers to pseudorotation for the interconversion of the above conformations <78JA433> also took into account the apicophilicities of the P-bound atoms. This was achieved using an element effect based on electronegativity preferences for the t.b.p. axial, equatorial, and s.p. apical and basal orientated atoms, which were then optimized to obtain the best fit with recorded barrier energies. In 1989 a set of force field parameters which include 1-3 interactions have been developed for molecular mechanics calculations of phosphoranes including those for hydridospirophosphorane (61; X = O, Y = Z = NH) <89CCllO3>.

1142

Compounds containing a Spiro Phosphorus Atom Table 9 Five coordinate spirophosphoranes with P-bound atoms = C3X2. Bul P-0

(38)

(37)

(40)

Y— O Y—

.»\ A r

(42)

(41) m

«

2 2 2 3 3 3 3 3 4 4 4 4 4 4 4

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

(43)

Ref

Compound

o2 s2 o2 o2 o2 o2 o2 o2 o2 o2 o2 o2 o2 o2

CIO

(44)

(37; Ch = O, R = CMe2CMe2) (37; Ch = S, R = CCF 3 =CCF 3 ) (38; X = CN) (39) (40; Y = CH 2 CH 2 , R = Ph) (40; Y = C[CF3]2C[CF3]2, R = 4-Br-Ph) (40; Y = 1,3-cyclopentyl, R = Ph) (40; Y = [CH2]4, R = Ph) (41; R1 = Me, Et, R3 = CH2CH2) (41; R1 = Et, R2 = H, R3 = C6H4) (41; R1 = Ph, R2 = Me, R3 = C6H4) (42; Y = Z = CO, R = Me, Ph) (42; Y = CMe2, Z = CO, R = Me) (43; Y = CMe2) (44; X = CF3)

78CC854 74J A317 90TL3429 73JCS(Pl)1300 78IC3265 74JA4143 83JOC2621 77PS(3)51 71JGU471 75JGU686 77JA3332 75CC399 79JA3687 76ZN(B)948 88ZAAC(561)49

Table 10 Five coordinate spirophosphoranes with P-bound atoms = C2X3.

R2

P.'' Me

1

R

\

o

(45) m

n

2 4 4 4 4 4 4 4

4 4 4 4 4 4 4 5

(47)

(46) Compound

O2X o3 o3 o3 NO 2 FO 2 N2O O2P

(38; X = Br, Cl, F, N3) (42; Y = Z = CO, R = OH) Hydroxyphosphorane (42; R = OH, Y = Z = CMe2) (42; R = OH, Y = Z = C(CF3)2) (45; R = H, X = CH 2 , Y = CHR, Z = CO) (46) (47) (48)

(48)

Ref 90TL3429 79JA3687 79JA4618 81JA1049 78IZV2185 70CC476 89PS(45)255 88CB391

Compounds containing a Spiro Phosphorus Atom

1143

Table 11 Five coordinate spirophosphoranes with P-bound atoms = CX4. O

R2 N ,Y N - P- N - R 2

R1

O

Me

0

N R-N CO2R

O-P

P-P

Me

X

Ar

N X

Ri'

O

O

R2

R

(50)

(49)

O (51)

(52)

R1 N

N H

Z

V

I

Y

P-NH N

O

1

R (54)

(53)

(56)

R

O

Ph O-P O

O-P

(58)

(57)

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

n 3 4 4 4 4 4 4 4 4 4 5 5 6 7 5 6

O

Compound N4 o4 N3P N2O2 o4 NO 3 NO 3 N2O2 O2S2 s4 o4 o4 O2S2 o4 o4 o4

1

2

(49; R , R = Me, Y = Me) Horner Intermediate (50) (51; R = Me, Ar = Ph) (52; R = Me, X = NHR, Y = NR, Z = PR) (53; R1 = Ph, R2 = Me, X = OMe, Y = Ac, Z = Pnc) (52; R = Me, Ph, X = Ph, Y = NMe, Z = CHMeCHPh) (45; R1 = Ph, R2 = Ar, X = O, Y, Z = CHMeCHPh) (54) (55; X = O, R = Ph) (55; X = S; R = Ph) (56; X, Y = O, R = Ph, Z = CPh = CPh) (56; R = OMe, X = O, Y = CH 2 , Z = C H = C H ) (57) (58; n = 5) (56; R = Ph, X = O, Z = CH 2 CMe 2 CH 2 ) (59; Y = Ph)

Ref. 95ZAAC(621)2001 79TL2203 81CB2132 85JGU2327 72CR(C)288 92JOC5195 75JCS(P1)2376 77CB1124 78JOM( 156)253 78JOM(156)253 91IC1052 77IZV2000 83JOC3815 79CC191 77JCS(P1)8O 92IC5494

8.41.3 EXPERIMENTAL STRUCTURAL METHODS 8.41.3.1

X-ray diffraction

X-ray diffraction studies of four coordinate phosphonium compounds include the cyclotriphosphazenes (21) <79ZN(B)9ll> and (7; X = NMe2, Y = NH, Z = CH 2 CH2) <78ZN(B)588>, and the bis spirophosphazene (84) <82IC3916>.

1144

Compounds containing a Spiro Phosphorus Atom Table 12 Five coordinate spirophosphoranes with P-bound atoms = HX4, O

Y\

o-

\

o

Y-P-Z Y X

O

(60)

m

n

4 4 4 4 4

4 4 4 4 5

(61)

Ref

Compound

o4 X 2 YZ N2O2 N2O2 o4

(60; Y = CMe2, Z = H) (61; X, Y, Z = O, S, NH) (62; R = H, X = O, Y = Z = NH) (63; X = NH, Y = CMe2, Z = H) (63; X = O, Y = (CH2)3, Z = H)

79TL4205 75BSF407 75JGU252 75CR(C)809 86PS(27)321

Table 13 Five coordinate spirophosphoranes with P-bound atoms = X5. X

Z R2 I

R1

R1

(65)

(64)

3 3 3 4 4 4 4 4 4 6

OH MeN

N-P-.

i

N-Y

m

R2

O

n 3 4 4 4 4 5 5 5 10 6

(68)

(67)

Ref.

Compound 2

84JA7065 76JCS(D)306 90PS(54)227 75PS(5)285 75TL2529 76CC1031 93PS(78)271 91JA7945 84JGU1754 77PS(3)35

(49;R',R = Me, Y = N3) (64; R1, R2 = Me, X = O, Y = PF 3 , Z = F) (65; R1, R2 = Me, X1 = NMe, X2 = N + Me 2 , Y = (CH 2 CH 2 ), Z = T (52; R = Ph, X = NMe 2 , Y = NMe, Z = CHMeCHPh) (66; n = 2, R = H, X = O, Y = O, Z = NMe2) (66; n = 3, R = CF 3 , X = NMeY = O, Z = OAr) (67; Y = C6H4) intermediate (68) crown ethers (63; X = O, Y = (CH 2 CH 2 O) 2 CH 2 CH 2 (59; Y = F)

N5 FN 2 O 2 IN 4 N2O3 NO 4 NO 4 N3O3 o3s2 O4X FO 4

Table 14 Five coordinate bis spirophosphoranes.

YN

(

Me Me Me \

X P

Bu

Bul

l

R

(69) m

n

X.

3 3 4

4 4 4

C2N3 N3O2 C1N4

X* (70)

Compound (69; R = CO2Me) (70; R = Ph, X = N 3 , Y = Glc) (71)

N | ! NV O

O

N

N

1

I

N

Me Me Me (71)

Ref. 86TL2863 83JGU247 70ZAAC(372)285

Compounds containing a Spiro Phosphorus Atom

1145

Table 15 Five coordinate spirophosphoranes incorporating a bridgehead phos phorus. Ph N P O I

i

O P N (72)

(74)

(73) O Me II Me i Jx^ i

,. Me

.. Me

O

O N Me

m

n

0

x$

3 3 3 3 5

4 4 3 5 5

4 4 3 5 5

CN 2 O 2 N3O2 NO 4 N4O o5

I ¥ I Me II Me O (75)

Me (76)

Ref.

Compound (72) (73) (74; Ch = O, R = CF3) (75) (76)

87CC1131 78CB2086 80JA5073 86PS(26)193 70CR(C)418

Table 16 Six coordinate mono and bis spiroperphosphoranides F6P

\— P v R

OXO \ I/ P | OyO

R (77)

R

m

R

P-X

-/ P

Cl m

O

n

4 4 4 3 4 4 4 4 4 4 5

4 4 4 4 4 4 4 4 4 4 5

0

4 4 4 4 4 5 5 5

Xe HNO 4 HO 5 N2O4 N2O4 Q o6 o6 CNO 4 o6 o6

NMe2

+£ Me

(82)

(81) n

o

N

n

m

+

(79) I

N

z

n

Me O

Y m

(78)

Ph

x

Compound +

(77; R = Me, X = C 5 H 5 N , Y = H) (78; R = CO2Me, X = OCHRCHROH, Y = H) (77; R = H, X = Y = C 5 H 5 N + ) (79; m = l , n = 2, R = H, X = NPh, Y = (PhNH) 2 P + ) (80; m = 0, n = 3) (79; m = 0, n = 3, R = Pr1, Z = Et 3 N + H) (81;m = 0, n = 3) (79; m = 0, n = 3, R = H, Z = Et 3 N + H) (82) (79; m = 1, n = 2, X = O, Y = CMe=CHC + Me) (79; X = O, Y = Bip, Z = brucineH)

Ref. 74CR(C)1353 79PS(6)435 78ZN(B)583 90JGU1491 70JCS(B)640 76JA6755 77ZAAC(437)53 73JA3154 93PS(75)233 79PS(7)305 79TL795

Compounds containing a Spiro Phosphorus Atom

1146

Ph Me

N Me XmCl

Me

A N

N

»

Ph

Ph (83) R = CF 3

(84)

Many five coordinate phosphorane compounds have been examined, the keen interest arising primarily from the variation of structures which have relevance with respect to their stereochemical importance as reactive intermediates in the reaction pathways of four coordinate compounds <74JA4143>. The stereochemistry of phosphoranes vary on a structural coordinate between trigonal bipyramidal (t.b.p.) and square pyramidal (s.p.). Phosphoranes which have been found to have conformations closer to the t.b.p stereochemistry include thienyl phosphorane (33; R1 = H, R2 = 2thienyl) <83ZN(B)466>, spiro(4,4)phosphoranes (41) <77JA3332>, (47) <89PS(45)255>, (42; R = Ph, Y = C(O)O) <79JA3687>, (85; R = CO2Me, X = OMe, Y = O, Z = CMe2CMe2) <81TL3533, 82AX(B)3024>, (49; R1 = Me, R2 = C 6 H 4 CF 3 , Y = C6F5) <8OCB1847>, hydroxyphosphorane (60; Y = CPh2, Z = OH) <82JCR(S)18O>, (55; X = S, R = Ph) <78JOM(156)253>, (55; X = S, R = Me) <73CC144>, (86; X = O, R = Ph, Cl) <77IC2294, 77JA3326>, (86; n = 2, X = O, S; R = adamantyl) <78IC3265>, (86; X = O, S; R = OPh) <76JOC473, 79JA3790), (66; X = Y = S, Z = Ph, R = CF3) <74PS(4)203>, (87; R = H, X = OMe, Ch = Se, Y = C(CF3)2, Z = N = CNMe2) <78AG(E)774>, (88; X = NMe, Y = CHMe, Z = CHPh) <8lPS(ll)87> (64; R1 = H, R2 = Me, X = O, Y = CH 2 CH 2 , Z = NPr 2 ) <84MI 841-01 >, (81; n = 2, X = Cl) <78PS(5)217>, the phenolic derivative (89; R = Bul Y = Ar) <84JSK568>, as well as some spiro(4,5)phosphoranes such as (90; n = 3, Y = OAr) <91IC1O52>, (66; n = 3, R = CF 3 , X = NMe, Y = O, Z = OAr) <76CClO3l>, (56; R = OAr, X = O, Y = NH, Z = oC6H3R2) <91IC3928>, (67; Y = Pfp, Z = NMe) <93PS(78)27i, 95CB627), and (91) <85CC1764> and some spiro(6,6)phosphoranes (59) <92IC5494>. Whereas there are a number of phosphoranes whose structure tend towards a r.p. geometry such as phosphetans (92; X = CF 3 , Y = Ar) <74ZN(B)32> and (92; X = H, Y = Ar) <78IC3265>, (51; R, Ar = Ph) <79CB1365>, (49; R1, R2 = Me, Y = Ph2P) <83ZN(B)702>, and phospholanes (93; X = S, Y = Ph, Z = Ar) <75CC773>, (94; R = Me, X = S, Y = O, Z = Ph) <83IC1771>, (86; R = Me, X = O) <74AX(B)935>, the tetrachloro and octachloro derivatives of (86; X = O, R = Ph) <79IC1668>, (66; n = 2, R = CF 3 X = Y = O; Z = Ph, Bul) <78IC3276>, (64; R1, R2 = Me, X = Tec, Y = CS, Z = NR 2 ) <92PS(73)195>. These trends have been reviewed <74JA4143> and the factors contributing to their conformational preferences studied (see Section 8.41.2) <75JA5379>. Whilst four and five membered rings almost without exception bridge apical-equatorial positions, six membered rings commonly follow this trend also and in the case of spirophosphorane (90; n = 3) this occurs despite the fact that this requires a sulfur atom to occupy an apical position in preference to an electronegative aryloxy group <90JA6092>. Intermolecular hydrogen bonding was found in the crystal spirophosphorane (86; R = CH2C1, X = NH) <9UGU1344>. Structural studies include several hydridospirophosphoranes, for example (86; R = H, X = NH) <78IC327O>, (95; R1 = H, R2 = R3 = Me) <7lMl 841-01). Whilst some NMR studies have found hydrogen to have a suprisingly high apicophilicity, in the crystal it usually occupies an equatorial orientation.

o-P

Y

b-P-x

Ch (85)

(86)

(87)

(88)

There have been x-ray diffraction studies of spirophosphoranes which also incoporate a bridgehead phosphorus atom of the type (96) <76CC449, 79ZN(B)906, 80CB1406, 90JA7451, 96PS(109)629), as well as some bis spirophosphoranes such as (70; Y = Glc) (77CB1887,77MI841-01,78TL2857,81CC810). There have been x-ray diffraction studies of several six coordinate perphosphoranides, for example (77) <78ZN(B)583>, (79; R = H) <73JA3154>, the potassium salt of (79; R = Bu{) <88MI 841-01 >, (97; R = CF 3 , X = OPh) <79PS(5)323>.

Compounds containing a Spiro Phosphorus Atom

1147

R R

o O-P;"Ph

o-p-o p ">OAr \ S X (CH 2 )n

X X

(90)

(92)

(91)

X Y

(93)

(95)

(94)

O--P-O X R (96)

8.41.3.2 8.413,2.1

(97)

Magnetic Resonance NMR Spectroscopy

The power of NMR spectroscopy for the study of phosphorus compounds is greatly enhanced not only by the structural dependence of 31P NMR chemical shifts but also through the couplings it produces in ! H and 13C spectra (B-91MI841-01 >. Like all chemical shifts 31P NMR chemical shifts are dependent on the coordination state, the directly bound atoms as well as stereochemistry. Of particular relevance to spiro compounds is the fact that the incorporation of five valent phosphorus into a small ring such as a 5 or 4 membered one, generally causes the signal to move downfield, whereas incorporation into a six membered ring usually causes the signal to move upfield. Following this trend the rare tetrathiophosphonium salts (24; R = (CH2)2) and (24; R = (CH2)3) have dP 147 and 110 ppm <83ZN(B)1O46>. The four coordinate group includes the spirophosphoranides such as (31; Y = Me) whose SP —34 ppm <78JA5229> is well upfield of related phosphonium salts at SP 50 ppm despite any small ring effect <79JA4623, 91MI 841-01 >. Since large atoms such as bromine and iodine bound to phosphorus usually cause the phosphorus signal to move upfield in phosphonia compounds, this effect balances small ring trends and an intermediate shift SP —109 ppm is observed, for spiro(3,3)phosphorane (65; R = Me, X1 = NMe, X2 = N + Me 2 , Y = CH2CH2, Z = I) <90PS(54)227>, and <5P -132.6 ppm for silyl derivative (86; X = O, R = TMS) <86PS(27)297>. However contradicting the large atom effect bromophosphorane (86; X = O, R = Br) is reported as having <5P - 2 8 ppm <82PS(13)157>.

The pentaaryl spiro(4,4)phosphoranes have chemical shifts SP — 88 to —98 ppm which move downfield as oxygen replaces P-bound carbon c.f. tetraoxaspirophosphoranes <8lPS(l0)395,91MI84101 >. Indeed the presence of two five membered rings in spirodoxaphosphoranes (98) can cause the 31 P NMR signal to move as far downfield as 27 ppm <72JA9264>. Dioxaphosphirane (37; Ch = O, R = CMe2CMe2) has SP —87 ppm which is well upfield of related 4,5 and 5,4 spirophosphoranes indicating that the small ring effect for three membered phosphiranes is in the opposite direction to those of 4 and 5 membered rings <78CC854>. On the other hand the presence of sulfur atoms bound

1148

Compounds containing a Spiro Phosphorus Atom

to phosphorus, for example (90; n = 2, Y = Me) <88PS(35)133>, (99; X = Y = Pfp, Z = SH) SP 14.2 ppm <85ZN(B)1589>, and (60; Y = CMe2, Z = S~) SP - 4 . 3 ppm <84CC225> exerts the usual deshielding effect.

x-

c (98)

P-Z

(99)

Variable temperature *H NMR studies of phosphoranes (33; R1 = Me, R2 = Ph) <69TL3423, 79CB218) and (66; R = Me, Y = O, Z = H) <69CC443> were among the first to investigate the pseudorotation process <74JA5398> and also highlighted the possibility of isolating chiral compounds. The spiro structure has been used to stabilise Wittig intermediates (35) sufficiently to establish their stereochemistry by NMR and follow their conversion to alkenes (87TL3445,90JA3905). Variable temperature NMR studies of the pseudorotation process i.e. ligand positional exchange, have been carried out on a wide range of spiro structures, for example (53; R1 = Me, Ph, R2 = H, X = Y = Ph, OEt, NEt 2 , Z = Glc, Tic) <76TL749, 78JGU650), (52) <75PS(5)73, 92JOC5195>, (45) <75JCS(Pl)2376>, and hydridophosphoranes such as (99; X = Glc, Y = Amc, Z = H) <78BSF(2)65>.

The pseudorotation barriers of spirophosphoranes such as (92) and (99: X = Y = Dnp, Z = R) <7lPS(l)9l, 77JCSP(l)437> and for hydridophosphoranes (66; R = CF 3 , X = Y = O, Z = H) <86PS(27)32l, 86ZOBH93) are dependent on ring size. Comparisons have also been made between spiro(4,5) and spiro(5,6) pentaoxophosphoranes, for example (99; X = Bio, Y = Bid, Z = OAc) <90JA6095>. Pseudorotation barriers have been used to estimate the apicophilicities of P-bound atoms or groups Y in (92) <7iccioi l >, and (99; X = Cat, Y = Pfp) acknowledging the limitations and assessing the accuracies <74JCS(P1)2125>. In general the more electronegative atoms or groups dominate the apical position of a t.b.p. However together two small rings tend to dominate both apical and two equatorial positions thus tending to push the noncyclic group into an equatorial position. In the case of spiro(3,3)phosphorane, for example (64; X = O, Z = F) <76JCS(D)306>, a fluorine atom was thought to be forced into an equatorial position of a t.b.p. However for the spiro(4,4)phosphorane (86; X = O, R = F) it is possible for the molecule to adopt the square pyramidal geometry shown <74ZN(B)32>. This may also be the case for the fluorophosphorane (46) (70CC476). A further increase in ring size, as in spiro(6,6) phosphorane (59; Y = F) <77PS(3)35> allows the fluorine to re-occupy the apical position of a t.b.p. On the other hand bulky groups favor the more spacious equatorial (radial) positions whereas small groups, for example hydrogen, have a strong tendency to occupy the apical position <74JCS(P1)2125>. This latter result threw doubt on many previous assumptions that hydrogen would prefer an equatorial position, for example <69CC443>. In a study of (53; R1 = Ph, R2 = Me, X = OAr, Y = Ac, Z = 2-SC6H4O) <8UCS(Pl)3074> sulfur showed no tendency to occupy the apical position, whereas the noncyclic group Y in (99; X = Cat, Y = Pfp) (99; X = Glc, Y = Pfp) and (53; R1 = Ph, R2 = Me, Y = Ac, Z = Pnc), ethoxy and thioethoxy groups exhibited the same apicophilicity <77JCS(P1)273>. Spirophosphorane (99; X = Pnc, Y = Tcc, Z = CN, Cl, NCO, NCS, N 3 , OPh) has also been used to study apicophilicities of group Z <79PS(7)167>. The configuration of spirophosphoranes (53; R1, R2, Y = H, X = OMe, Z = O(CH2)2CHMe) was studied by *H NMR Spectroscopy <72DOK(205)1370, 72PAS717).

Vicinal spin-spin coupling constants through saturated carbon in spirophosphoranes may be quite large, for example 28.8 Hz for (99; X, Y = Oam, Z = CH2C1) <72JGU1895> and has been shown to be 22 and 45.9 Hz for the cis and trans isomers of tetraoxaphosphorane (99; X = Y = Glc, Z = CE = CHE) <76CR(C)849>. PCH geminal couplings are 11 Hz for (33; R1 = H, R2 = Me), 24.3 for (33; R1 = H, R2 = CH = CMe2) a case being made for these couplings to be positive in comparison with the negative phosphonium salt geminal couplings <7OJCS(C)1425>. The couplings 'Jpn ca 770 of hydridospirophosphoranes of the type (99; X = Y = Eta, Z = H) tend to be at the lower end of the phosphorane series <70CR(C)865> and 2 J PN H 21 Hz was recorded for hydridophosphorane (100; R = Me, X = Glc, Y = H) <72CR(C)1413>. Coupling constant ^pp was 270 and 156 Hz for phosphines (49; Y = Ph2P) <83ZN(B)702> and (51), and larger, as expected, (709 Hz) for the phosphonate (49; R \ R2 = Me, Y = (EtO)2P(O) <82IC844>. Six coordinate spiroperphosphoranides have 31P chemical shifts in the range —57 to —181 ppm upfield of the corresponding five coordinate phosphoranes but towards the low field region of the range (<5P —57 to —440) for all six coordinate compounds , for example (80; m = 0,

Compounds containing a Spiro Phosphorus Atom

1149

n = 3) <5P - 1 8 1 ppm <65CB576>, (101; X = Y = Bip, Z = Cat), and (101; X = Y = Bip, Z = Don) SP — 147 and —168 ppm respectively <76CB1O56>, (101; X = Y = Z = Glc) <5P - 8 9 ppm <71CC1O7O>, (101; X = Y = Bip) SP - 82 ppm <65CB576,77ZOB1432). The methyl groups of the 2-propyl derivative of perphosphoranide (79; m = 0, n = 3, R = Pr1) have been shown to be diastereotopic <76PS(6)9l>.

8.41.3.2.2

Electron spin resonance spectrometry

The variable temperature ESR spectra of the spirophosphorus radical (Pnc2P*) indicated that pseudo rotation is slow even at 120°C, AG* being 54 klmol" 1 <72JOM(42)C47>. Spin labeled spirophosphoranes (99; X = Glc, Y = Dme, Z = Nox) <78ZN(B)305>, and (87; Y = odd electron • ) have been reported <78BAU1O64>. A deep violet color develops when hydridobisphenylenephosphorane (33; R = H) dissolved in benzene is kept in the dark. Although this was attributed to the bisphenylene phosphoryl radical an ESR spectrum was not reported <69CB528>.

8.41.3.3

Mass Spectrometry

The mass spectra of spirobiphenylenephosphoranes (33) show abundant M-l and M-R2 fragments and there was a tendency to form doubly charged ions <73PS(2)167>. The mass spectra of cyclophosphazenes such as (7) <76ZAAC(426)275> have been used to identify substitution patterns around the rings. Migration of groups to and from phosphorus is common and therefore mass spectral results must be interpreted with care.

8.41.3.4

Electronic Spectroscopy, Circular Polarization, and Polarimetry

Phosphorus, whilst having an auxochromic effect, does not transmit conjugation effects from one chromophore to another. Thus the UV spectra of spirobiphenylene-phosphoranes were dominated by the biphenyl ring system. Comparisons of the spectra with the precursor dibiphenylene phosphonium salt and pentaphenylphosphoranes showed the spirophosphoranes to have more bands than the salt. This was attributed to different auxochromic effects of phosphorus through apical and equatorial bonds. <7OJCS(C)1425>. The kinetics of isomerization of ephidrene based hydridospiro(4,4)-phosphoranes <74TL397l) and related L-alanine based phosphoranes <80PS(8)i53> can be followed by polarimetry. The molecular rotation of optically active spiro(4,4)hydridodioxa-phosphoranes (61; X = O, Y, Z = NR), and ephidrene derived (99; X = Glc, Y = Eph, Z = H), permitted the separation of rotational contributions from the ligands and the helix structures. This allowed the assignment of the absolute configuration of a large number of phosphoranes <8lPS(l0)53>. The polarimetric temperature jump method has been used to obtain more accurate kinetic and thermodynamic parameters for the isomerization of hydridophosphoranes (99; X = Eta, Y = Eph, Z = H) <77JCS(D)570>. Six coordinate perphosphoranide (101; X = Y = Cat, Z = OCHPhCO2) was isolated in one form

1150

Compounds containing a Spiro Phosphorus Atom

by second order asymetric induction. Its equilibration was studied by polarimetry <76JCS(P2)955). Circular dichroism of trisbiphenyleneperphophoranide showed that the (— )-stereoisomer has a left handed screw stereochemistry <70JCS(B)640>. 8.41.3.5

Vibrational Spectroscopy

Whilst infrared spectroscopy is used extensively as additional evidence for structural assignments there have been relatively few studies which focus on this area. One such study involved hydridospirophosphorane (94; R1 = R2 = Me, R3 = H) where the vNH solvent dependence resembled pyrrole and vPH correlated with 'Jpn <69SA(A)l20l, 72CR(C)1156>. Ring-chain isomerism and hydrogen bonding of hydridophosphorane (99; X = Pnc, Y = Pda, Z = H) was studied by IR spectroscopy <75CR(C)809>.

8.41.4

THERMODYNAMIC ASPECTS

The barriers to intramolecular ligand exchange (permutational isomerism) via a pseudo rotation process have been measured for a large number of five coordinate phosphoranes using the variable temperature NMR signal coalescence approach (see 8.41.3.2.1). Care has to be taken to check that a dissociation-association mechanism is not operating, thus low AS* and lack of deuterium exchange was used as evidence for the absence of a dissociation mechanism <74JCS(P2)1668>. For the spirophosphoranes the largest barriers are observed when isomerism requires the formation of a conformer with a small ring bridging two equatorial (radial) orientations. The barrier to interconversion of isomeric phosphinates via spiro(3,4)hydroxyphosphoranes was shown to be AG* = 17 kcal mol" 1 by variable temperature NMR spectroscopy <76TL438l, 79JCS(Pl)879> c.f. AG* = 24 kcal mol" 1 for the pseudorotation barriers of dimethylaminospirophosphorane derived from cis cyclohexane diol <75JGU2088>.

8.41.5

REACTIVITY OF FULLY CONJUGATED RINGS

There are no fully conjugated spirophosphorus compounds. 8.41.6 8.41.6.1

REACTIVITY OF NONCONJUGATED RINGS Spirophosphonium Salts and Ylides

The extrusion of disulfide from spirophosphazene (24; X = S, Y = (CH2)3) provides a useful route to two coordinate triazaphosphole (102) <76T2039>. The related extrusion reaction of (103) includes the loss of dimethylamine (Equation (1)) <80TLl307>. In some cases there is an equilibrium between the phosphorane, for example (57) and the phospholan plus disulfide <83JOC3815>. Spirophosphonium ylide (11) can be converted to its lithium diylide which forms a nickel complex <8lCB3l6l). Spirophosphoranide (31; Y = CF3) has also been converted to a series of metal complexes <93PS(76)87>.

Me (102)

S—P-N-R

(103)

(1)

Compounds containing a Spiro Phosphorus Atom 8.41.6.2

1151

Spirophosphoranes

The stabilities of spirophosphoranes vary widely. Whilst small rings induce stability, they are not always sufficient to ensure a stable phosphorane. Thus triphenylphosphole reacts with two equivalents of ethyne dicarboxylate to give a transient spirophosphorane (104) but this rearranges spontaneously to give the ylide (105) (Equation (2)) <68T3437>. The saturated analogues, for example phosphorane (2; m = n = 3, Y = Me) can be isolated but this is probably due to the lack of a rearrangement or degradation pathway rather than having thermodynamic stability. Two electronegative atoms are usually desirable. Some spirophosphoranes, for example (106; X1 = H, X2 = X3 = X4 = Me, Y = Glc, Z = OAc) are stable under quite vigorous reaction conditions <7UGU228> whereas others (107) can slowly ring open to give the carboxylic acid isomer <79JCR(S)172> or exist in equilibrium with the open chain form <74BSF2193>. Monocyclic phosphoranes undergo 1,2-aryl migration from phosphorus to carbon under thermal conditions and in some cases spontaneously (6UCS2126, 71PS(1)139>. The thermally induced rearrangement of spirobiphenylenephosphoranes (33; R1 = H) to phosphines (108) and (109) are further examples, the former predominating when R2 is Me or Ph, the latter predominating if R is larger, for example anthryl <76CB1497>. The reaction of phospholene (110; Y = Ph) with a peroxide gave P-phenyldioxaphosphepan which was rationalised as involving an unstable spiro(4,6)phosphorane shown in Scheme 1 <74PS(4)265>. Similarly spirophosphorane (34) formed in cycloaddition reactions underwent retrocycloaddition <83TL583l>. Spirophosphiranes (37) undergo related reactions <78CC854,74JA317). On the other hand heating the urea derived spiro(3,4)phosphorane (65; X1 = NMe, X2 = PPh, Y = CONMe) gave phosphole (111) as if by hydrolysis <81CB2132>. The bis spirophosphorane (70; R = Ph, X = OEt, Y = Dpe, Pfp) fragmented in a similar manner <76BCJ1924>.

(2) E = CO2Me E

(104)

(105)

O

(107)

(106)

(108)

(109)

Y\

O i

P-o i

o

o

(110) Scheme 1 Me

O

Me

N

O

Ph

(HI)

Whilst spirophosphetanes (35) have been generated for reactivity studies via the Wittig reaction, they have also been generated as oxyanions (35; R1 = O~, R2 = R3 = Ph) from /Miydroxyalkylphosphine oxides and found to fragment stereospecifically to cis stilbene <85JCS(P1)1953>. Another exam-

1152

Compounds containing a Spiro Phosphorus Atom

pie is the detection of a related glycolyl oxyanion in a Horner reaction <79TL2203>. A related spiro oxyanion (112) fragments with the formation of an aziridine <(79E85l>. The formation and isolation of a spiro oxaphosphetan was achieved via a Horner reaction of a ketone with an oxyanion followed by cyclization as shown in Equation (3) <92JA4008>.

(112)

X X

(3) H2C-

-N

There have been a number of studies of the hydrolysis of spirophosphoranes. These include a range of spirotetraoxyphosphoranes (66) <79PS(6)435>, (106; X1 = CONH 2 , X2 = H, X3 = X4 = OMe, Y = Pnc) <90PS(47)443>, (99; X = Y = Plc, Z = Ph) <85JA5198>, and of dioxyphosphoranes (41) the products of which were characterized by acylation <72JGU782>. The hydrolysis of hydroxyphosphoranes (42; R = OH, Y = CMe2) have also been studied <86JA2416>. Cycloaddition reactions of an aminodioxaphosphole with chalcone gave a spiro(4,4)phosphorane <(82PS(13)85> which undergoes ring expansion to give a spiro(4,6)phosphorane as shown in in Equation (4) <(85PS(25)319>.

(4)

PhCO

Spiro(2,4)phosphorane (113) was a postulated intermediate in the formation of bis spirophosphorane (114) from a dioxaphospholan and benzaldehyde (Equation (5)) <88CC615>. Thermal cleavage of phosphazenes to a phosphole as shown in Scheme 2 is rationalized as involving a spiro(4,5)phosphorane <74JCS(P1)1694>. Hydridospirophosphorane (60; Y = CH2, Z = H) in the presence of a tertiary amine has been used to convert ketocarboxylic acids such as pyruvates into the corresponding a-hydroxycarboxylates <92PS(70)263>. However in aqueous alcohol hydridophosphoranes such as (99; X = Glc, Y = Amc, Z = H) are converted to phosph(III)olanes <8OPS(9)183>.

Me

(113)

8.41.6.3

(5)

(114)

Spiroperphosphoranides

The interconversion and cis: trans isomerization of six coordinate spiroperphosphoranides (115; X = Gls, Y = Pfe, Z = OC 6 H 4 F, R = F) have been studied <8UCR(S)218>. Five and six coordinate

Compounds containing a Spiro Phosphorus Atom

1153

N

N

Ph Ph'

\

Scheme 2

structures are often in equilibrium, the latter usually being favored over the five coordinate structure in compounds such as (116) (79T1825). The equilibrium shown in Scheme 3 (R1 = Ph, CF3, CC13; R2 = Me, 2-Pr, X = Y = Cat) was found to depend on solvent and temperature <85ZOB1982>. A quite remarkable reaction shown in Equation (6) involves a 1,3 migration of a dimethylamino group (Y) from one phosphorus atom to the other at some stage during the reaction <(93PS(75)233>.

Xr-x R

(116)

(115)

c

r

c

Me 1

Me

Me

R

N R

V

R2

2

Scheme 3

Me2N

NMe 2 \ Me

Me 2 N Me

Me

(6)

Tcc~-^

O

Me

8.41.7 REACTIVITY OF SUBSTITUENTS ATTACHED TO RING CARBON The tendency for reactivity to focus at phosphorus leads to relatively few reports on the reactivity of carbon substituents. The 1,3-allylic migration of a methoxy group across a spirooxyphospholene ring was induced by heating at 140 °C for 10 minutes (Scheme 4) <(85PS(24)235>. Secondary amines and phosphorous esters add to the activated double bond of spirophosphorane (99; X = Y = Glc, Z = CE=CHE) <79CR(C)165>. Spiroperphosphoranide (117) reacts with trimethyl phosphite as shown in Equation (7) <79PS(7)305>.

(MeO)3P

(7) P(OMe)2

(117)

1154

Compounds containing a Spiro Phosphorus Atom MeO OMe

MeO MeO 140 °C

MeO—\ Q MeO2C

2 min

O OMe

140 °C

MeO Me2NOC

10 min

Me2NOC

Scheme 4

8.41.8

REACTIVITY OF SUBSTITUENTS ATTACHED TO RING HETEROATOMS INCLUDING SPIRO PHOSPHORUS

The physical and chemical properties of the hydrido P—H group in spirophosphoranes have been studied. The pK a 's of hydridophosphoranes (62; X = O, NH) were found to be 5.89 and 11.96 <77IZV434>. Hydridophosphorane (60; Y = CMe2, CPh2, Z = H) was oxidized to the corresponding hydroxyphosphorane by N 2 O 4 in DMSO which was then in equilibrium with the open chain carboxylic acid <80T2467>. The PH bond of hydridophosphoranes undergoes many addition reactions to unsaturated compounds <79PS(7)8l>, thus (61; X = Y = Z = O) adds to chloral or benzaldehyde, <68CR(C)270>, (61; X = Y = O, Z = O/NH) adds to acrylic ester in the presence of alkoxide to give Michael adduct (99; X = Glc, Y = Glc/Gln, Z = CH 2 CH 2 E, Z = O/NH) <70BAU2637>, and in a similar manner hydridophosphoranes adds to imines <74CR(C)l30l>. Addition reactions of hydridophosphoranes to unsaturated compounds such as vinylethyl ether and alkynic carboxylic esters can be achieved using an AIBN catalyst, thus compounds such as (99; X = Y = Glc, Z = CH 2 CH 2 OEt/CE=CHE) have been made this way <76T2253, 79CR(C)165, 81PS(9)285>. However di-tbutylperoxide converts (66; X = Y = Pnc, Z = H) into the phosphate (118) <85JGU181O> and dimethyldisulfide under photolysis conditions converts (99; X = Glc, Y = Pfp, Z = H) into (99; X = Glc, Y = Pfp, Z = MeS) <86PS(27)313>. Interestingly, methanol and an enamine (which is hydrogenated) converts the PH group of hydridospirophosphoranes (61; X = Y = Z = O) directly to the corresponding methoxyspirophosphorane <76T2253>, whereas the P-H group of (60; Y = CPh2, Z = H) is oxidized to its hydroxyphosphorane by DMSO in DMF <78CC219> and is converted by sodamide or butyllithium into phosphoranides which can be acylated or alkylated to give spirophosphoranes (60; Z = R or PhCO) <75JCS(P1)122O, 75JOM(93)33l, 79TL4205). However, in some cases the intermediate perphosphoranide is in equilibrium with the ring opened isomer (78JA7434). The P—H bond has also been converted to P—Hal <83ZAAC(507)93>, P—S", P—Se~, P—NTs", P—PS2Ar~, <87PS(32)l>, and P—BH3 <88PS(35)309>. Photolysis of the azide (99; X = Y = Cat, Z = N3) gave a nitrene which abstracted hydrogen from the solvent (benzene) to give the amino derivative (99; X = Y = Cat, Z = NH 2 ) <84JA7065>, and a related azide of spiro(3,3)phosphorane (49; R1, R2 = Me, Y = N3) was reacted with Ph3P <86PS(26)193> to give the corresponding phosphazene.

(118)

The chlorine atom of (86; X = O, R = Cl) was reacted with Y-TMS; Y = Ph2P, CN, Br, I, MgTMS, N = C H P h , to produce the derivatives (49; R1, R2 = Me, Y = Ph2P, CN, Br, I, TMS, N=CHPh) <83ZAAC(507)702, 85JGU2333, 86PS(27)297, 91PS(62)139>, and

with

(EtO) 2 P(O)Na

to

give

(49;

Y = (EtO)2P(O)) <82IC844>. P-Halo perfluoropinacol-spirophosphoranes (99; X = Y = Pfc, Z = Hal) react with aq. KOH to give an isolable potassium salt (99; X = Y = Pfc, Z = O~) and with alcohols to give stable alkoxy derivatives (99; X = Y = Pfc, Z = OR) which can be sublimed from sulfuric acid <82AG(E)208>. In the case of an ambident nucleophile (EtO)2NHAr, a P—P bond was formed initially upon reaction with (86; X = O, Y = Cl) and this was followed by rearrangement to the PNP isomer <86JGU2218>. In the case of chlorophosphorane (119), dimethylamine replaced chlorine (at — 78°C in THF) with inversion whereas reaction with PhONa was nonstereospecific <79TL193>. Bromophosphorane (86; X = O, Y = Br) reacted with chloral to give (86; X = O, Y = POCHBrCCl3) <89JGU2583). Exocyclic P—N bonds are also readily substituted and provide ready routes to alkoxy and carboxy derivatives (99; X = Pnc, Y = Dpe, Z = OR/OCOPh) <73TL3455>. When one of the rings has a carboxy group (99; X = Glc, Y = Hyc) compounds with exocyclic groups Z = PhO or

Compounds containing a Spiro Phosphorus Atom

1155

X 3 CCH 2 O are readily converted to alkoxy groups by the action of alcohol <8OCL1599>. Also an exocyclic vinyl ether group can be replaced by Br by the action of bromine which in turn may be converted to methoxy by methanol <84JGU486>. The chlorine in (86; R = Cl, X = O) has also been replaced by Mn(CO) 5 <83ICAL139>.

ci o-p-o

(119)

Methylation of hydroxyphosphorane (42; R = OH, Y = CO) by diazomethane gives the methoxy derivative (42; R = OMe, Y = CO), whereas methylmagnesium iodide gives trimethylated phosphorane (42; R = Me, Y = CO, Z = CMe2) <79JA3687>. Whilst the NH group of spirophosphorane (120; R1 = R2 = H, R3 = R4 = Ph) was methylated by KH and Mel to give (120; R1 = Me, R2 - H, R3 = R4 = Ph) <90PS(49)385>, when the phosphorane also had a PH group as in (120; R1 = H, R2 = R3 = Me; R4 = H) NaH and Mel methylated at phosphorus to give (120; R1 = H; R2 = R3 = R4 = Me) <84CJC2179>. The bis spirophosphorane (121) was made by the reaction of hydridophosphorane (60; Y = CMe2, Z = H) with phenyldichlorophosphine (90T3527).

O

(120)

(121)

The six coordinate hydridospiroperphosphoranide (115; R = H, X = Y = Cat, Z = Et) on standing for several days with 2-aminophenol undergoes conversion to phosphorane (99; X = Cat, Y = Oam, Z = Et) probably with loss of hydroquinone <75JGU2292>.

8.41.9

RING SYNTHESES

8.41.9.1 8.41.9,1 A

All Components Acyclic Spirophosphonia compounds

Spiro(4,4)phosphonianonane triiodide (1; m = n = 4) was prepared (40%) by heating phosphorus and 1,4-diiodobutane at 200 °C <68ZOB33i, 77AG(E)722>. The dibenzo derivative (8) was prepared from o-xylidene dibromide <73JHC395>. The tetrabenzo salts (9) may be made from dilithium biphenyl and either trichlorophosphine <72RTC836> or triphenyl phosphate <73RTCl308> or by the original method involving bis di-iodobiphenyl and phosphorus <65CB576>. When the aryl ring is activated towards electrophilic attack as in diphenylamine, trichlorophosphine is able to substitute at the ortho position and, at 200 °C, ultimately produce the spirophosphonium salt (13) <71CC1213>. If the forming bond to phosphorus is from a heteroatom, a P(III) phosphorus can be made electrophilic. Such an example is the the cyclization of the dibenzyl ether (122) to give phosphorane (42; Y, Z = CH2, R = Ph) as shown in Scheme 5 <82JCS(P1)735>. Spiro(5,5)phosphonia-undecane chloride (12) was produced in low yield by the reaction of dimethylurea with the little exploited, readily available, tetrakis(hydroxymethyl)-phosphonium salts <81PS(1O)147>. Tetrathiodibenzo quasiphosphonium salts (24; R = Dop; X~ = PF 6 ~) have been produced by the reaction of silylated dithiocatechol (123) with PF 5 <73CC144>. Spiro(5,5)phosphazenes (20) may be made directly from trichlorophosphine and diaminophosphazene, H 2 NPR 2 =PR 2 NH 2 ,

1156

Compounds containing a Spiro Phosphorus Atom „ Bn

/%.

o

^ \

if^*r Br2

P"Ph

'

, Bn

B r

o

+P 'Ph

+P "Ph

Br

iT^r V

Bn

(42)

Br^ )

R = Ph Y = CH,

(122) Scheme 5

<75CB1454>. On the other hand, bis spirophosphazene (27) was made by the reaction of substituted phosphabenzenes with phenylazide <93TL3107>. Rhenium carbonyls have been used to dicyclize a silylated diphosphazene to produce the salt (17) <87CB1183>. TMS

(123)

8.41.9.1.2

Spirophosphoranes

The formation of phosphoranes is greatly enhanced when the phosphorus atom is involved in a rive membered ring which has apical electronegative atoms such as oxygen. Thus pentachlorophosphorane (PC15) reacts with acylhydrazines to give P-chloro spirophosphoranes <89JGU1333>, and with o-methylaminothiophenol to give chlorophosphorane (55; X = NH, R = Cl) <77JGU436>. Also intramolecular addition of a benzylic alcohol to the phosphoryl group gives an intermediate hydroxyphosphorane which undergoes intramolecular condensation to produce the spirophosphorane as shown in Scheme 6 <78JA513O>. "OH

en /«=\

Gc\ /=\

Scheme 6

The dilithium salt (124) with POC13 gives, after work up and treatment with KOH, the dibenzospirophosphorane potassium salt (42; Y = C(CF3)2, R = OK) <81JOC1049>. Hexachlorocyclotriphosphazene, (NPC12)3, may be used as a source of phosphorus in place of PC13, thus with o-aminophenol, spirophosphorane (86; X = NH, R = o-OC6H4NH2) may be obtained via a NH bridged bis spiro compound <75IC283l>. Methyltetraphenoxyphosphorane, prepared from methyltriphenoxyphosphonium iodide, using (MeO) 2 CCHNMe 2 , was converted by ethane- 1,2-diol to the spirophosphorane (66; R = CF 3 , X = Y = O, Z = NMe 2 ) <89JGU634>. Analagous reactions occur when pentaphenoxyphosphorane, (PhO)5P, reacts with catechol <68T504l> and with o-aminophenol <76IZV2624>, as well as for the reactions of pentaethoxyphosphoranes, (EtO)5P, with diols <71JA4004>. Silylated oxygen or sulfur functional groups react with RPF 4 to produce phosphoranes (99; X = Y = Cat, Z = F, Et, Prj, CH 2 TMS) <7UCS(A)1295>, its naphthdiol analogue (99; X = Y = Don), <92PS(69)23l>, (99; X = Y = Ami, Z = H) <92CB80l> and (55; X = S) <73CC144>. The use of trisphosphoramidites, for example (Me2N)3P, often has advantages over trichlorophosphine with amidrazones to give hydridophosphoranes (99; X = Y = Ami, Z = H) <72CR(C)2209>. They have also been used in combination with CC14 in which case the reaction proceeds via quaziphosphonium salts <75TL2529>. The P—N bonds are quite labile and strong acids are not generated. Thus spirophosphorane (54) has been prepared by the reaction of either RP(Ch)Cl2 or

Compounds containing a Spiro Phosphorus Atom

1157

MeP(NMe 2 ) 2 with a hydrazide RCONHNH 2 <77CB1124>. Also two equivalents of the Mannich base of 2-cresol were reacted with (Et2N)3P to generate a spirophosphorane with two P—C bonds <67DOK(174)846). There are a number of examples of the oxidative cyclization of monocyclic hydridophosphoranes to give spirophosphoranes as shown in Equation (8) and Scheme 7 <75TL497>. The deoxygenation of nitrobenzene derivatives by P(III) compounds can be used to make intermediate cyclic phosphoranes which react with o-aminophenols with migration of an aryl group from oxygen to nitrogen (Scheme 8) <75JCS(P1)2376>. Hydrido-phosphoranes may be prepared directly from trichlorophosphine, for example (60; Y = CR2, Z = H) from a-hydroxcarboxylic acids <71BSF4185> including tartaric, malic acid <8lPS(ll)71>, and enolisable a-ketocarboxylic acids <88PS(35)195>. Likewise, (62; R = Bu', X = Y = Z = O) was made using di-t-butylcatechol <88JGU1996>. Me

Me

,'VU NMe2

HO^XH

R-Px

O(CH2)nXH -

R-P

NMe 2

•

O(CH2)BXH

R-P,

•

R~P^

O(CH2) XH

o3

Scheme 7 Me MoP(OEt)2 N

NO

°Et

x

2

A

^ / ^ N

N I

I

Ar R Scheme 8

8.41.9.1.3

Perphosphoranides

Very stable perphosphoranides may be prepared directly (79; m = 0, n = 3, R = H) from catechol and PC13 or POC13 <76TL917> or PC15 <77JPR188>, (81; m = 0, n = 3) from PC13 and N-benzoylhydroxylamime <77ZAAC(437)53>. White phosphorus reacts with 3,4-di-t-butylbenzoquinone in the presence of triethylamine to give (79; R = Bu', m = 0, n = 3) (79IZV2398). The phosphorus atom is invariably spiro to three identical rings.

8.41.9.2 8.41.9.2.1

From One Monocyclic Component Spirophosphonia compounds

Spiro(5,5)phosphonium bromide (1; m = n = 5) was synthesized from 1-methylphosphorinan by monoalkylation with 1,4-dibromobutane followed by ylide intramolecular alkylation as shown in Scheme 9 <80ZN(B)990>. Dilithium biphenyl reacted with the phenylphosphine oxide (125) to displace

1158

Compounds containing a Spiro Phosphorus Atom

the phenyl and oxygen and give the cage salt (10; R = H) <72CC404>. Generation of an electrophilic centre by protonation of an allenylphosphonate was followed by cyclization to the phosphoryl oxygen to give spiro trioxonium salts as shown in Scheme 10 <84PS(2l)249>. Me

Me

I

Br (8) m = n = 5 Scheme 9

(125)

Scheme 10

A wide variety of spiro(5,5)phosphazenes may be prepared from hexachlorocyclo-triphosphazene by the replacement of two chlorine atoms by aromatic diamines or aminophenol (85JA7585,88IC1911) or by a sequence of condensing reagents, for example AgNCO, ROH, MeCN <87PS(30)5l9>. This approach has also been used to generate many bis spiro compounds <82ZN(B)1425> including 1,3dioxaphosphorins <84CC675>, and incorporating salicylate moieties <75ICA24O>, as well as hydrazine <89ZN(B)612> and thioferrocene <90ZN(B)741>, as well as spermine bridges, for example (29) <84JST(116)75>. Some reactions are accelerated by the presence of Bu 4 N + X~ <83MM719>. Alternatively the addition of a second ring may be achieved by condensation of difunctional reagents with the geminal amino groups bound to phosphorus as shown in Equation (9) <76PS(6)ll3>. In the case of supermesitylmagnesium bromide, following substitution of one chlorine atom of hexachlorocyclotriphosphazene, the intermediate can be ring closed from phosphorus to one of the tbutyl methyl groups, under the action of A1C13, to give spirophosphazene (15) <90JCS(D)2303>. Five membered phosphazenes (126) derived from PC13 and amidrazones, react with propanedithiol to produce spirophosphazene (24; X = S, Y = (CH2)3) <76T2039> and eight membered octachlorocyclotetraphosphazenes with propanediols give the corresponding spirophosphazenes <91PS(55)59>. R2 P-N

R2 NH2 NH2

Cl-V C1

2Hr, ~2HC1

_p' Cl-

(126)

Lithium biphenylenephosphoranide (127) which may be prepared by the action of butyllithium on the fluorenylphosphine (128; Y = Br), is in equilibrium with the ring opened isomer (128; Y = Li) <69CB548>. In most cases the phosphoranides are produced by the action of base on the corresponding hydridophosphoranes <79JA4623>.

Compounds containing a Spiro Phosphorus Atom

(127)

8.41.9.2.2

1159

(128)

Spirophosphoranes

Dioxyspirophosphoranes can be prepared either by displacement of two fluorine atoms on phosphorus i.e. (129; R = Ph), by the dilithium salt of diols, or by cycloaddition, for example, using a-diketones <7OCRC(C)418, 75T797) (see Section 8.41.9.3). On the other hand the catecholspirophosphoranes were prepared from difluorophosphoranes (129; R = Ph, Me, Bu', F) by condensation with trimethylsilanyl derivatives of catechol (78IJ107,78IJ143). Monocyclic phosphoranes with leaving groups other than halogen can also be used (e.g., methoxy, or dimethylamino) in reactions with diols and amino alcohols <72PS(2)41,75PS(5)285>. These reactions can be exothermic.

R

R-V-° P-F R

(129)

Many phosphorus(III) compounds add to two equivalents of compounds possessing electrophilic multiple bonds such as carbonyl groups and electrophilically activated double and triple bonds. The driving force for the second stage (a 1,3 polar addition) is usually the formation of a phosphorane incorporating a small ring. Whilst the reaction of triphenylphosphole with DMAD gives the spirophosphorane (104), it is not stable <68T3437>. However the use of a phosphorus(III) 1,3dioxaphospholan adds stability. Thus pinacol derived methoxyphospholan (130) reacts with two equivalents of DMAD to give a spirophosphorane as shown in Scheme 11 <81TL3533>. Whilst benzaldehyde adds in the normal head to tail mode with catechol derived phospholan as shown in Equation (10) <76JGU58l>, substituted benzaldehydes with 1,3-diazaphospholan gave head to head spiro adducts (131) <68JOC13> Carbonyl compounds such as hexafluoroacetone are better able to support negative charge on carbon when attacked at oxygen in the initial step <74JCS(P1)2125, 93PS(78)271,95PS(1O6)65>. Benzophenone and PhCOCN <75CR(C)225> also give head to head products as shown in Scheme 12. Similar reactions occur with chloral and tribromoacetaldehyde <87JGU1O78>. MeO

P-OMe

—E

o

(130)

Ph

P-NEt 2

~o

2 PhCHO

(10) NEt 2

1160

Compounds containing a Spiro Phosphorus Atom

-Ar

-N OAr (131)

X

Y

< X

"P-R

Scheme 12

Phosphonium ylides (132) react exothermically with oxiran but a temperature of 130°C is required to achieve reactions with oxetan to give oxaphosphoranes shown in Equation (11) (79CB501). A stabilized ylide cyclized on heating at 140°C and 150°C to give the amides shown in Scheme 4 <85PS(24)235>. It is possible that an ylide may be also formed in the reaction of benzylphosphetan with hexafluoroacetone in the formation of phosphoranylspiro(3,3)oxaheptane as shown in Scheme 13 <73JCS(Pl)1300>.

CH2

Y

Y

>

P

(>)„

(11)

Me

Me

CF 3

'"' Ph

Ph

Ph

Ph

CF 3

CF3

CF, •o=<

CF,

CF3

CF,

CF,

Scheme 13

Phosphazene (133) generated from a phospholan and phenyl azide was cyclized as shown in Equation (12) <76CC730>. Stabilized phosphazenes, for example (134) have also been cyclized in this way <78JGU13O8>. The PhN=functionality can also act as a leaving group, thus phosphazene (135) was reacted with C2 to C 5 diols with loss of aniline to produce spirophosphoranes (Equation (13)) (58; Y = Ph) <79CC191>. An alternative approach involves the reaction of a functionalized azide, for example 2-azidophenol with cyclic phosphines to give intermediates set up for cyclization via addition to the P = N bond as in Scheme 14 <8OPS(8)127>. Similarly, phosphazene (136) gives spirophosphorane (120; R1 = R2 = H, R3 = R4 = Ph) (Equation (14)) <90PS(49)385>. Related phosphazene intermediates were proposed in the reaction pathway shown in Scheme 15. It has two interesting features, first the use of a dialkylamino leaving group, secondly, the nitrogen to phosphorus migration to produce a phosphazene function to which the second hydroxyl group cyclizes <90JGU397>. -O O R

(133)

I"

(12)

Compounds containing a Spiro Phosphorus Atom

1161

ArO 2 S (134) Ph Ph

Ph

Ph Ph

-N

P-Ph N3

o

Ph

Ph

Ph

HO HO Scheme 14 O Ph \ / P

HO

H»

(58) Y = Ph

(13)

-PhNH 2

(135) Ph OH

LA

(120)

R1 = R2 = H R3 = R4 = P h

(14)

O (136) HO_

^-NEt2 HO

V-NEt2

J

/^ N EHOt 2

f

^ \

P

O

o-

> 7

O

O

o o

~NEt2

~NEt2

Scheme 15

The reaction of cyclic three coordinate phosphorus compounds with diols has been found to proceed smoothly in the presence of di-isopropylchloramine (ClPri2) <75TL1583>. This reaction would appear to involve initial formation of an amino salt which reacts with one of the alcoholic hydroxyl groups followed by cyclization and loss of amine after protonation by the liberated HCl as shown in Scheme 16. If the P(III) atom already bears a potential leaving group such as SEt, it is possible to use an activating group such as ethyl acrylate as in Scheme 17 <83PS(l 7)283 >. On the other hand [2 + 4] cycloaddition reactions with dichlorophosphines produce directly a phosphonium center, for example (137) suitable for reacting with diols and diamines etc. to give spirocompounds such as (47) <89PS(45)255>. Unsaturated carboxylic acids add to cyclic P(III) compound (138; Ch = O) to give an hydridophosphorane which cyclizes by Michael addition of the PH group to the acrylic moiety (Scheme 18) <78IZV2185>. HO ClNPr1,

ciNPr'j

HO -HCl

O

Scheme 16

Spiro hydridophosphoranes may be prepared by a condensation reaction of P-halo or P-aminodioxaphospholanes and 1,2-aminoalcohols (139; X = NH, Y = CH2) <72BSF1413, 72CR(C)419> or

Compounds containing a Spiro Phosphorus Atom

1162

R P-SEt

Y

Scheme 17

Ph I N ' N\ Ph I P+

"ci

Ph

Ph (137)

O Et

X~~ H

Ch P-Et N H (138)

Et

N'

O

Scheme 18

amino acids (139; X = NH, Y = CO) <77T635> as in Equation (15). Alternatively routes to intermediates involve the reaction of PC13 with the magnesium salt of the benzyl alcohol (140) (Scheme 19) <79JA4623>. The alkyl substituents R assist the electrocyclization. Similar reactions with hydrazides and amidoximes (RC(=NOH)NH 2 ) give hydridophosphoranes (99; X = Pnc, Y = Amo, Z = H) <72CR(C)l5l> (99; X = Glc, Y = Amo, Z = H) <82CB2560>, and (99; X = Cat, Y = Amo, Z = H) <72CRC1211>. HO,

O

O(15)

P-Z HX

R O Mg (140)

PC1 3

I R R (139)

(42) R =H Y = Z = CR2

Compounds containing a Spiro Phosphorus Atom

1163

There were a number of reports in the 1970s of monocyclic hydrido phosphoranes acting as intermediates in the formation of spirophosphoranes. Thus hydridophosphoranes convert to phosphoranes slowly but spontaneously when X = O, and on heating or with a mild oxidizing agent when X = NH <75TL3077, 83JGV1759) as shown in Equation (8). Monocyclic phosphoranes (141) are converted at 160°C to spiro(4,5)phosphorane (Scheme 20). The yields are higher as the donor properties of Z increase <86T352l>. Note that this argues against a transition state with phenoxide character for the migration and in favor of alkoxy phosphonium character to give an ylide which, after proton transfer to the ylidic carbon with rearomatization, recyclizes. An alkylarylether oxygen will cyclize to a phosphonium center with dealkylation by bromide ion as shown in Equation (16) <79PS(7)57>. A similar ring closure was achieved with transfer of a trimethylsilyl group to a phosphoryl group as in Equation (17) <76JA4330>.

T-^

MeU

.}

o—P Y (141)

^ /

\

MeO

160 °C

Y

Br ' '

/ '

(99) \

= =

/

(16)

X = Y = Cat Z = Br

-

(99)

(17)

X = Y = Cat Z = O-TMS

8.41.9.2.3

Spiroperphosphoranides

Perphosphoranides with phosphorus spiro to three rings one of which is different from the other two (e.g. 101; X = Y = Cat, Z = Dpe) may be prepared by the reaction of a monocyclic phosphorane bearing three exocyclic dimethylamino leaving groups and a chelating ligand such as catechol <75PS(5)285>.

8.41.9.3 8.41.9.3.1

By 2 + 4 Cycloaddition to Phosphorus Spirophosphonia compounds

Two coordinate phosphines are able to participate as dienophiles in cycloaddition reactions with 1,3-dienes and their hetero analogues such as diimines, a-diketones, and unsaturated ketones etc. to produce four coordinate spiro compounds. Thus cyclic two coordinate phospholes, for example (102) add to diacetyl <84TL552l>, diimine R N = C R C R = N R ) <86TL2971>, and to azodicarboxylic esters <81CB825> to give the corresponding spirophosphazenes (23). In the case of the product from diacetyl, a dimer is formed initially. It is also possible to have the phosphorus III atom as part of the 4 electron system adding to an activated carbonyl group as the dienophile as shown in Equation (18) <82JGU189>. OEt

o S

P-N

O

PhCOCN

^ O E t Ph

f

L *

(18>

' Ph

1164 8.41.9.3.2

Compounds containing a Spiro Phosphorus Atom Spirophosphoranes

The reactions of three coordinate phosphines with 1,3-dienes and their hetero analogues such as diimines, a-diketones and unsaturated ketones etc. to produce five coordinate spiro phosphoranes has been widely exploited. Thus 1,3-butadiene reacts with catechol phosphonous esters to produce dioxaphosphoranes (142) <69TL4693>, the reaction rate increasing with increasing electron accepting properties of group Y <72JGU782>. Ortho quinones such as di-t-butylbenzoquinone <94ZN(B)145>, phenanthraquinone <68T1785>, and tetrachloro-ortho-quinone <96S473> make excellent 4p-7t compounds, the increase in aromaticity and formation of stable P—O bonds strongly favoring the forward reaction. Thus these are favorite reagents for producing spirophosphoranes with three P—C bonds (72JA9264, 80CB1406). This reaction may be extended to a-diketones <70CRC(C)418, 75T797), ketoesters <92JGU1172>, azoketones <72CR(C)419> and isatin <85JGU1986>. Aliphatic spirophosphoranes, for example (143) with two PC bonds have been prepared from methoxyphospholenes and diacetyl <89PS(44)193> or benzil <85JGU1514>. A novel approach involved cycloaddition of two equivalents of benzil to PhP (phenylphosphinidene), or its equivalent, generated either from (PhP)5 at 160°C or photochemically, to give (99; X = Y = Dpe, Z = Ph) <68CB1381, 7UCS(C)593>. A range of phosphoranes (53; R2 = Y = H, Z = Glc) have been prepared from unsaturated aldehydes <82JGU22l> extending previous studies of unsaturated ketones, carboxylic acids, and amides, and other phospholans. Cycloadditions to the dioxaphospholan was found to be faster than with the corresponding benzodioxaphospholan <(72JGU21O9>. As above, it is also possible to have the phosphorus III atom as part of the 4 electron system adding to an activated carbonyl group as the dienophile. In the example shown in Scheme 21 the addition occurs twice to produce the bridged spirophosphorane (144) <90JA745l>. Ozone adds to dioxabenzophospholans and dioxaphosphinans to give stable spiro ozonides (145; Y = Cat) and (145; Y = Pic) <84PS(20)55>.

coo (142)

O

Ph

y (144) Scheme 21

OMe O O

I.

(143)

8.41.9.4 8.41.9.4.1

RO

.A

V (145)

By 2 + 2 Cycloaddition to Phosphorus Spirophosphoranes

The reaction of cyclic three coordinate phosphorus compounds with cyclic peroxides and disulfides gives valence expanded spirophosphoranes with a wide range of ring size possibilities as shown in Equation (19). Thus phenylphosphetan reacted with cyclic peroxides and also with a disulfide to give phosphoranes (40; Y = (CH2)4) <77PS(3)5i>, (40; R = Ph, Y = 1,3-cyclopentanylidene) <83JOC2621> and disulfide (146) <72CC395>, and (147) <84MI 841-02, 84MI 84l-03> respectively. In the

Compounds containing a Spiro Phosphorus Atom

1165

case of cyclic diselenides (148), one selenium is removed and the remaining fragment forms part of the spirophosphorane (87; Ch = Se, Y = C(CF3)2, Z = N = NMe2) <78AG(E)774>

Ph

CF3 CF3 (146)

R

R

(19)

SAr

(147)

There are many examples of monocyclic phosphazenes dimerizing to give spiro(3,4)phosphoranes <75CB820, 92JGU780, 92JGU970). Supermesitylphosphine reacts with diazodicarboxylic ester to give diphosphazene (149; R = Bu\ Y = CO2R) which, at 110°C, undergoes CH addition (from a methyl group) to a P = N bond at both phosphorus centers to give bis spirophosphorane (69) <88PS(35)247>. There are other examples of ortho t-butyl groups reacting in this way.

R

R (149)

8.41.9.5

By Ring Modification

8,41,9,5.1

Spirophosphonia compounds

Chlorospiro-phosphoranes, under the action of Lewis acids such as SbCl5, may be converted to the quasiphosphonium salt, for example (16) <88ZAAC(56l)49>. Hydroxyphosphorane (42; R = OH, Y = CMe2) is converted to the spiroquasiphosphonium triflate (14) by the action of trifluoromethanesulphonic acid <78JA5229>; this in turn can be reduced by LAH to the phosphoranide (42; R = electron pair, Y = CMe2).

8,41,9,5,2 Spirophosphoranes Phosphoranes such as phosphoranylspiro (4,4)nonane (2; m = n = 3, Y = Me) and the biphenylene phosphoranes (33) may be prepared by the reaction of lithium alkyls or lithium aryls with a spiro salt, for example (1; m = n = 4) <77AG(E)722> or (9) <77CB693>. Hydridobiphenylenephosphoranes (33; R = H) have also been prepared by LAH or borohydride reduction of the biphenylene salt (9) <69CB528>.

Azodicarboxylic ester can be used as an activating agent for P(III) compounds undergoing [2 + 4]

1166

Compounds containing a Spiro Phosphorus Atom

cycloaddition reactions to give phosphoranes such as (150) and then being replaced by reagents such as diols liberating the reduced azoester as its hydrazine <8OTL1449>. Diphenyldisulphide, PhSSPh, has also been used as a condensing agent <82JOC916>; whilst a quasiphosphonium salt was proposed as an intermediate, a dithiophosphorane intermediate is quite possible. OR

(150)

Spirophosphorane (65; X1 = MeN, X2 = PC 6 H 5 , Y = CONAr) was formed in the reaction of a disilylated derivative of urea with dichloro(perfluorophenyl)phosphine, presumably the expected eight membered ring rearranging as shown in Scheme 22 <79CB1365>. Treatment of the corresponding product from PhPCl2, with Cl2 and PC15 removed one of the phosphorus groups and gave spirophosphorane (49; Y = Ph) <80CB1847>. o Ar

Me

Ar-NYN~Me

TMS TMS

O Ar = m-CF3C6H4 Scheme 22

8.41.9.6 8.41.9.6.1

Other Methods Spirophosphoranes

Aniline hydrochloride converts the azathiobenzophospholan (138; Ch = S) to spirophosphorane (151) <83JGU1759>. Presumably the aniline releases some aminothiophenol forming a hydridophosphorane which spontaneously dehydrogenates similar to that reported in Equation (8)). Et

N H

N H

(151)

8.41.9.6.2

Spiroperphosphoranides

Many six coordinate spiroperphosphoranides have been obtained by addition of a nucleophile to the phosphorus atom of a spirophosophorane. Thus the nucleophiles fluoride or p-fluorophenoxy anions gave (115; X = Glc, Y = Pfe, Z = F/ArO) <80CC157>, pyridine gave (115; X = Cat, Y = Pfe, Z = PhO, R = NC 5 H 5 ) •(74JA7269), and alcohols reacted with a hydridophosphorane to produce (115; R = H, X = Y = Cat, Z = OR) <73CR(C)297>. Spirophosphoranes (99; X = Y = Cat, Z = Hal) bearing an exocyclic leaving group (Y) such as halogen react with chelates such as bipyridyl giving (152) <79PS(7)305>, 2-ketopyridines, and /?diketones giving (153) and with trisaminophosphazene (154) to give perphosphoranide (155) (Equation (20)) <90JGUl49l>. When spirophosphoranes have a second nucleophilic center juxtaposed to the phosphorus atom there is a potential for the formation of a perphosphoranide. Examples include

Compounds containing a Spiro Phosphorus Atom

1167

the 8-hydroxyquinoline compound (116) <79T1825>. Spirophosphorus atoms participating in three different ring types, for example 101; X = Glc, Y = Dpe, Z = Hyc) have been prepared by taking a spirophosphorane possessing two different ring types and an exocyclic leaving group <75BSF1433>.

(152)

(153)

Ph N NHPh Cat 2 P^ j V

(PhNH)3P = NPh

(20)

Ph (154)

8.41.10 8.41.10.1

(155)

IMPORTANT COMPOUNDS AND APPLICATIONS Nonmedical Applications

The tris spirocyclotriazene (156), prepared via condensation polymers <75MI 841-01), has been used to form clathrate tunnels in which alkenes can be polymerized with enhanced stereoregularity <82MM697>. These compounds are able to form inclusion complexes with />-xylene thus offering a useful means of purification <72BRP12570247>. They have also been patented in a number of countries as flame retardants <75GEP(O)231350-1 >. Attempts to polymerize spirocyclotriphosphazenes (157) produced ring expanded products <93MM3>.

N

"N

RO

(156)

OR

(157)

The fluoride ion in the tetraaza analogue of the fenestrane related phosphonium fluoride (158) is an example of a completely ionic fluoride ion <8UA5265>. The ozonide (159) from an adamantyl type phosphite is a good water soluble source of singlet oxygen and is 1.4 times more stable than ozonide (160) <75JOC1185>.

A

°

Et

o o o (158)

(159)

(160)

1168 8.41.10.2

Compounds containing a Spiro Phosphorus Atom Compounds of Medical Interest

A series of bis cyclotriphosphazenyl spermines such as (161) have been prepared and shown to have anticancer activity in six murine tumour systems. These compounds had a higher potency and lower toxicity than related aziran derivatives <87PS(29)147>. Spirophosphorane derivatives of thymidine such as (162; R = CF3) have been used as models for the study of the stereochemistry of cyclic AMP interactions with enzymes <90JA6092>. The base catalyzed proton transfer observed for the equilibrium shown in Scheme 23, mimics the role of the bases histidine 12 and histidine 119 in the active site of Rnase A during the hydrolysis of ribonucleic acids <84PS(19)173>.

(161)

OH

o HI P-

o o

o

o

Scheme 23

Copyright © 1996 Elsevier Ltd.

Comprehensive Heterocyclic Chemistry II