- Email: [email protected]
An efficient procedure for the synthesis of C-chiral bisphosphines
Vol. 51. No. 28. pp. 7655.7666, 1995 Copyright 0 1995 Elsevier Science Ltd Printed m Great Britain. All rights reserved
Tetrahedron
Pergamon
0040.4020/95
$9.50+0.00
0040-4020(95)00390-8
An Effkient
Procedure
for the Synthesis of C-Chiral
Lydia McKiiry
Bisphosphines.
and Tom Livinghouse”
Departmentof Chemistry and Biochemistry Montana StateUniversity Bozeman, MT 59717 U.S.A.
Abstract: A practical method for the synthesisof bisphosphks containing homochiml carbon backbonesis described. This procedure entails sequential reaction of a homochkal ditosylate with the appropriate dialkyl- or dkylphosphine-bon anion followed by BH, decomplexation mediatedby HBF,.OM+
Homochiralphosphines that form stereodifferentiated chelatecomplexeswith transitionmetalshave becomeindispensable tools for asymmetriccatalysis2 At the presenttime there is a noteworthy deficiency of general methodsfor the enantioselective synthesisof P-chiral phosphines.’In consequence, the largest
existingfamily of phosphines that havebeendevelopedfor asymmetriccatalysiscomprisesmoleculesin which stericdifferentiationat phosphorus is impartedby homochiralcarbonbackbones4The most commonlyutilized procedurefor the synthesisof manyof thesephosphines involves the alkylation of strong& basic diary1or dialkyl metallophosphides with the appropriatehomochiraldisulfonate.’ Unfortunately, this
methodis not alwaysreliablein that diminishedyieldsof the desiredsubstitutionproductcanresult asa consequence of competingsidereactionssuchas basemediated elimination,
electrontransferprocesses, etc.
Interveningreactionsof this variety are particularlyproblematicwhenvery basicmetalloderivativesof stericallyhindereddialkyl phosphines are usedasnucleophiles.For thesespecies,efficient carbonphosphorus bond formationis mosteffectively achievedby usinga homochiraldzjluorideas the substrate.6’7 Over the pastfew years, Imamotoandco-workershavepublisheda seriesof importantpaperson the syntheticutility of phosphine-borane complexes.’The nucleophilicbut mikiiy basic anionsderived from secondaryphosphine-boranes havebeenshownto undergoalkylation, 1,4-additionandPd(0) catalyzedcrosscouplingreactionswith a wide variety of commonsubstrates. 8 It is thereforesurprisingthat the potential utility of thesecomplexesfor the synthesisof bisphosphines containinghomochiralcarbon backboneshas beenlargely overlooked.’ We havepreviously communicated a versatilemethodfor the synthesisof C-chiral bisphosphines that relieson the alkylation of phosphine-borane anionswith homochiralditosylates.” Herein we provide a moredetailedaccountof this method. 7655
L. MCKINSTRY and T. LIVINGHOUSE
7656
The generalprocedurethat wasroutinely employedfor the synthesisof C-chiralbisphosphine-borane intermediates involvesthe deprotonationof the requisitemonophosphine-borane adductsbusing“alkoxide free” n-BuLi” (THF, -78 “C) followedby the additionof a DMF solutionof the homochiralditosylateof interest(-40 “C). Typically, the reactionmixture is thenstirred underargonat ambienttemperatureuntil complexesthat have been bis-alkylationhasbeenachieved(Scheme1).“9” A seriesof bisphosphine-borane synthesizedin this manneris shownin Table I. The preparativegeneralityof the aboveprocedurecan be inferred from the high yields obtainedfor the u,cr’-branchedcyclohexyl bearingbisphosphine-boranes 2d and 2c aswell asfor the stericallycongestedbis(diarylphosphine-borane) analog2f.
r \
-BHo \
OTs (RhP-BH3’
p+w2
u+ (
DMF - lHF
=
OTs
)”
(eql)
t
P+(R)2 I
4)
-BHB
(n=1,2) 1
Table I.
2
Synthesisof Representative Bisphosphine-boranes via NucleophilicDisplacementwith Phosphine-borane Anions.
2a ( 93 %)
2b ( 89 %)
HtB
2d ( 86 %)
-BH3
2e ( 88 %) ( Ar = 2-CH&(CH30)C&
1
7651
C-Chiral bisphosphines
The reported procedures for converting phosphine-boranes to the corresponding free phosphines involve heating the parent complexes with a large excess of a secondary amine (e.g., morpholine or diethyl amine)ab or DABCO. 9b Although 2e could be converted to bisphosphine 3e by either of the published procedures, the bisborane complexes 2b, 2c and 2d proved remarkablyresistanttoward aminemediatedBH, exchange. Even at elevatedtemperatures(e.g., 100 “C), thesecomplexeswere incompletelyconverted(-70-80%) to the correspondingbisphosphines.An examinationof other boraneadductsof hindered,electronrich phosphines further indicatedthat BH, decomplexationby amineexchangecart be an inefficient process. Presumably,the enhancedstrengthof the P-B bondin boranecomplexesof electronrich phosphines is responsiblefor the observedlethargy of 2b, k,
2d andother hinderedBH, adductstoward aminolysis. In light of this apparent
limitation, we setout to developan alternativeandcomplementarymethodfor phosphine-borane decomplexation.‘4Imamotohasrepoti
that representativesulfonicacidsreact with phosphine-boranes in
aproticmediato provide the correspondingboranesulfonatederivatives.*’ In a preliminary study to determineif this type of reactioncould serveasa basisfor phosphinedeprotection,DPPfi(BH,), (2i) was treatedwith a variety of acids(i.e., CH,SO,H, CF,SO,H, HBF,*OMq, etc., CHJI,, -5 “C - 25 “C) and subsequently hydrolyzed WaHCO, aq., 0 “C (10 min underAr) or K,CO, a&z., 25 “C (6.5 h underAr)]. A roughmeasureof the efficiency of decomplexationwasobtainedby TLC analysesof reactionaliquots. This procedurereadily mmkd
the stepwiseconversionof 2i to DPPE (3i) (Scheme2).15 Of the various
acids
that wereexamined,commercialHBF,*OM% proved the mostefficaciousin termsof rate aswell asisolated yield of free phosphine.16 Although reactionconditionscustomtailoredto a given phosphine-borane couldbe readily derived, thestandard conditionsthat were usedfor ail of the examplesdescribedhereinvolve treatmentwith HBF,*OMe, [(S equiv/P*BH, moiety), CH,Cl,, -5 “c - 25 “C, 12 h] followed by hydrolysis (NaHCOr~q., 0 “C). The resultsobtainedfor the decomplexationof a rangeof phosphine-boranes are illustratedin Table II.
n P+P), (PM’* I I H$ -B&j
21
a)
HBF,DMq *
b)
NaHCO, of KzC4
(a$) (an/~.) 31
7658
L. MCKINSTRY
Table II.
and T. LIVINGHOUSE
HBF,*OMe, Mediated Decomplexation of Representative Bisphosphine-boranes.
3a (97%)
3c (91%)
3j (98%)
3f (98%) [ Ar = 2-CH,4(CH,0)C6HJ
Me,
,Me S1
eP(Ph),
(‘1 PW
W’hh
W’hh
3g (89
1
%)
WW
/(Ph)
2
31 (92%)
3h (94%)
To gain insight into the prospective mechanism of decomplexation, methyldiphenylphosphine-borane (4) was treated with HBF,*OMe, (1 quiv) in CDCI,.
‘H
NMR
analysis revealed consumption of 4 with
concomitant formation of a product possessing a down field shifted methyl doublet of doublets at 2.41 ppm (Jn.r = 15.22 Hz and J+,-r = 5.82 Hz). In addition, “P NMR analysis revealed an up field shifted signal at 1.98 ppm (doublet of multiplets, .I,, = 521 Hz). The appearance of these new resonances is consistent with the intermediacy of the phosphine-fluoroborane complex 5 (eq 3).
-BH, I Ph)Z+P,CH
HBF;OMe,
(eq3) 3
C-Chiral bisphosphines
7659
As is evident from the examples presented above, the HBF,*OMe, decomplexation procedure can facilitate rapid access to certain electron rich homochiral bisphosphines that are otherwise very difficult to prepare. In addition, the conditions for decomplexation are sufficiently mild to permit the survival of the C-Si and ferrocenyl linkages of ligands 3g and 3h.17 It is also noteworthy that highly impure samples of valuable phosphines can be conveniently purified via the corresponding BH, adducts. For example, treatment of impure (lS,25’)-1,2-bis(diphenylphosphinomethyl)cyclohexane
(3a) (of 80% purity) with BH,rSM%
(2.1 equiv) followed by trituration with methanol gave the highly crystalline bisborane adduct. Decomplexation of this material in the usual manner returned pure 3a.
3a Contaminated bisphosphine
with IX. 20 % oxides
( > 99%
pure )
(eq4)
The efficient route to homochiral bisphosphine-boranes delineated here, when utilized in tandem with the convenient HBF,*OMe, decomplexation procedure, is expected to facilitate the preparation of a wide range of stereochemically varied phosphine ligands. The synthesis and utilization of these new chiral modifiers for asymmetric catalysis will be described in upcoming Acknowledgements.
accounts
from these laboratories.
Generous support for this research by grants from the National Institute of Health and
the National Science Foundation is gratefully acknowledged. EXPERIMENTAL General procedures.
SECTION
All reactions were performed in either oven-dried or flame-dried round- bottom
flasks fitted with rubber septa, under a positive pressure of argon, unless otherwise noted. Air- and moisture-sensitive liquids and solutions were transferred via syringe or stainless steel cannula. Organic solutions were concentrated by rotary evaporation at -25 Torr (water aspirator) with a Buchi rotary evaporator. Analytical gas chromatography was performed on a Varian Model 3700 Gas Chromatograph equipped with a flame ionization detector, a Hewlett-Packard 339oA reporting integrator and a
7660
L. MCKINSTRY
and T. LIVI~VGHOUSE
15 m X 0.54 mmID columnwith DB5 (or SE-45or equivalent)bondedphase. Preparativegas chromatographywasperformedon a Varian Model 3300 GasChromatographequippedwith a thermal conductivity detector,a Hewlett-Packard3390A reportingintegratoranda 1.8 m X 4 mmcolumnwith a 10%siliconeOV-17 chromosorbadsorbentphase.High PerformanceLiquid Chromatographywas performed
on an IBM LC/9533 Ternary GradientLiquid Chromatographequippedwith an IBM LC/9523
VariableW Detector. For generalanalyticalseparations an IBM 250 mm X 4.5 mmID columnpacked with IBM 5 pm sphericalsilicawasusedin conjunctionwith a Linear Model 156 chartrecorder. Flash columnchromatographywasperformedasdescribedby Still’B employingE. Merck 230-400ASTM mesh, 0.040-0.063mmparticle size, silicagel 60. Solvent systemsusedfor elutionare reportedin % volume/volume. Analytical thin-layer chromatographywasperformedusingK42-G platessuppliedby Alltech Associates. Materials. Commercialreagentsandsolventswereusedasreceivedwith the following exceptions. Tetrahydrofuran,1,2-dimethoxyethane,benzene,heptaneand hexanewere distilledfrom potassium.Diethyl etherwasdistilledfrom sodium-benzophenone ketyl. N,N-dimethylformamideandhexamethylphosphoric triamideweredistilledfrom calciumhydrideat 20Torr, while dichloromethane,acetonitrile,toluene and 2-butanolweredistilledfrom calciumhydrideat atmosphericpressureunderan inert atmosphere of argonor nitrogen. Purificationof methanolwasaccomplished by distillation from magnesium dimethoxideunderan atmosphere of argon. The molaritiesindicatedfor organolithiumreagentswere established by titration with a standardsolutionof 2-butanolin xylene using1,lo-phenanthrolineasindicator. Grignardreagentswere titrated in the samemanner. Periodicallythesereagentswere titrated for total basecontentwith a standard solutionof potassiumbiphthalateusingphenolphthalein asindicator. Instrumentation. Proton andcabon nuclearmagneticresonance(iH NMR and i3CNMR) spectra weremeasured at 300and 75 MHz, respectively,with a Bruker AC-300 spectrometer.Phosphorus nuclear magneticresonance (“P NMR) spectrawere measured at 202 MHz with a Bruker AM-500 spectrometer. Protonchemicalshiftsare reportedas6 valuesin partsper million down field from tetramethylsilaneandare referencedto residualprotium in the NMR solvent(CHCI,: 6 7.24, C,HD,: 6 7.15). Carbonchemical shiftsare reportedas6 valuesin partsper million down field from tetramethylsilane andare referencedto the 13Cin the NMR solvent(CDCI,: 6 77.0, C,D,: 6 128.0). Phosphorus chemicalshiftsare reportedas b values in partsper million down field from 85%aqueousphosphoricacid andare referencedinternally to the 3’Psignalin triphenyl phosphine(6 -6.0). Dataare representedasfollows: chemicalshift, multiplicity (s = singlet,d = doublet,t = triplet, q = quartet, m = multiplet), integration,couplingconstantin Hertz (Hz) andassignment.High resolutionmassspectrawere measured on a VG Analytical 7070Espectrometer by Dr. L. J. Sears. Infrared spectrawere recordedwith either a Bruker IFS 25 IR, a Perkin-Elmer1800 FTIR or a Perkin-Elmer237Bgrating IR. Melting pointswere determinedwith either a Fisher-Johns or a
C-Chiral bisphosphines
7661
Mel-Temp II melting point apparatus and are uncorrected. Optical rotations were measured with a PerkinElmer 241 C polarimeter. Elemental analysis was performed by Desert Analytics, Tucson, AZ. @icyclohexylphosphine)trihydroboron (6a). An oven-dried,round-bottomedflask fitted with a rubberseptumanda magneticstirringbar waschargedwith dicyclohexylphosphine(431 mg, 2.22 mmol, 1 equiv), diethyl ether (3.0 mL) andpurgedwith argon. The solutionwascooledto 0 “C, whereuponborane methyl sulfide(0.330 mL of a 10.1M solution,3.33 mmol, 1.5 equiv) wasaddedslowly by syringe. The reactionmixture waswarmedslowly to 25 “C andsubsequently stirredat this temperaturefor an additional 2 h. The solventswereevaporatedunderreducedpressureandthe resultingresiduewastriturated with three 2-mL portionsof diethyl ether to give 456 mg (99%) of 6a asa white solid: mp 78.6-80.9 “C; ‘H NMR (300 MHz, CDCl,) 6 4.11 (appd sx, J = 4.9 Hz, JH+ = 351 HZ, P-H), 1.80 (m, lOH, CHJ, 1.71 (br m, 2H, P-CH), 1.25 (m, lOH, CHJ, 0.40 (br q, JnB = 94.7 Hz, 3H, BH,); “C NMR (75 MHz, CDCl,, ‘H decoupled)6 29.4, 29.2, 28.8, 28.6, 27.7, 26.7, 26.5, 26.3, 25.7; 3’PNMR (202 MHz, CDCl,) 6 17.3 (br d, J,, = 351 Hz); IR (film) 2929,2853, 2382, 2350, 1449, 1062cm-i. Anal. Calcd. for C,,H,,BP: C, 67.93; H, 12.36; P, 14.61. Found: C, 68.14; H, 12.02; P, 14.50. (Diphenylphosphme)trihydroboron (6b). The reactionof diphenylphosphine (1.86 g, 10.0 mmol, 1 equiv) with boranemethyl sulfide(1.08 mL of a 10.2 M solution, 11.0 mmol, 1.1 equiv) wascarriedout asdescribedfor 6a. @iphenylphosphine)trihydroboron (6b) wasisolated(1.96 g, 98%) asa viscousclear oil: ‘H NMR (300 MHz, CDCl,) 6 7.68-7.61 (m, 2H, Ph-H), 7.50-7.41 (m, 8H, Ph-H), 6.29 (dq, J = 6.9 Hz, JHep= 378 Hz, lH, P-H), 1.07 (br q, JHe8= 97.3 Hz, 3H, BH,); “C NMR (75 MHz, CDC&, ‘H decoupled)6 133.1(CH), 132.9(CH), 131.6(CH), 129.2(CH), 129.0(CH), 128.5(c); “P NMR (202 MHz, CDCl,) 8 0.8 (d, JP.u= 337 Hz); IR (film) 2388, 1483,1438, 1109, 1059cm-‘. 4Lithio-3-methylanisole. An oven-dried,250 mL, three-necked,round-bottomedflask wasfitted with a pressureequalizingadditionfunnel, glassstopper,condenser,magneticstirring bar andglassbeads. The vesselwaspurgedwith argonandchargedwith diethyl ether(20 mL). The stopperwasremovedand replacedwith a conical funnelwhile a constantflow of argonwaspassedthrough the flask. Lithium wire, alloyedwith 1% sodium[0.385 g, 55.0 mmol, 2.2 equiv (prewashed with toluene)], washeld with forceps over the funneland cut with cleanscissorsinto 2 mmpiecessothat they droppeddirectly into the ether. A solutionof 4-bromo-3-methylanisole’9 (5.02 g, 25.0 mmol, 1 equiv) in diethyl ether (50 mL) wasadded slowly to the lithium suspension via additionfunnel, suchthat the reactionmixture wasmaintainedat reflux. Uponcompletionof the addition,the yellow solutionwasstirredvigorously at 25 “C for an additional3 h. Bis(4-methoxy-2-methylphenyl)-N,N-dimethyl~inoph~phine (7). An oven-dried, 250 mL, threenecked,round-bottomedflask wasfitted with a pressureequalizingaddition funnel, 2 glassstoppersand a magneticstirring bar. The vesselwaspurgedwith argon, chargedwith dichloro-N,N-dimethylaminophosphine2’ (1.83 g, 12.5 mmol, 1 equiv) in diethyl ether(50 mL) and cooledto -78 “C. A solutionof 4-lithio-3-methylanisole(70.0 mL of a 0.357 M solutionin diethyl ether, 25.0 mmol, 2 equiv) wasadded slowly via additionfunnel. Upon completionof the addition, the mixture waswarmedslowly to 25 “C over a periodof 1 h. After dilution with anhydrousdiethyl ether (20 mL), the mixture wasfiltered through activity II neutralaluminaundera constantflow of argonandconcentratedin vacua. The resultingresidue waspurified by distillation (160-165“C, 5 ~Torr) to afford 3.33 g (84%) of 7 asa highly viscouscolorless oil: ‘H NMR (300 MHz, CDCl,) 6 6.99 (dd, J = 3.9, 8.4 Hz, 2H, Ar-H), 6.70 (m, 4H, Ar-H), 3.78 (s, 6H, OCH,), 2.65 (d, J = 8.2 Hz, 6H, N(CH,)J, 2.27 (s, 6H, CH,); 3’PNMR (202 MHz, CDCl,) 6 49.7 (9. ~is(4-metboxy-2-metbylphenyl)phosphine]tribydroboron (6c). An oven-dried, 250 mL, threenecked,round-bottomedflask wasfitted with a glassstopper,a gas-inletadapteranda magneticstirringbar. The vesselwaspurgedwith argon, chargedwith 7 (0.850 g, 2.68 mmol, 1 equiv) in diethyl ether (107 mL) andcooledto 0 “C. Anhydroushydrogenchloride (0.219 g, 6.00 mmol, 2.2 equiv) wasslowly bubbledinto the solutionwhereupona white precipitateformed. The reactionmixture waswarmedto 25 “C and stirred
7662
L.
MCKINSTRY
and T. LIVINGHOUSE
for 5 h. The precipitateddimethylaminehydrochloridewasfiltered undera streamof argonand the filtrate wasconcentratedin vacua. The resultingbis(4-methoxy-2-methylphenyl)chlorophosphine wasredissolvedin tetrahydrofuran(1.5 mL) andaddedslowly, via additionfunnel, to an oven-dried,round-bottomedflask containinglithium aluminumhydride (0.122g, 3.20 mmol, 1.19 e&v), boranemethyl sulfide (0.320 mL of a 10.2 M solution,3.25 mmol, 1.25 equiv) and tetrahydrofuran(2.0 mL), at 0 “C. Upon completionof the addition, the mixture waswarmedto 25 “C and stirredfor an additional2 h. Excesslithium aluminum hydride wasquenchedwith aqueoushydrochloric acid (5 N, 1.5 mL) and ice (3.0 g), andthe biphasic mixture wasdiluted with diethyl ether (4.0 mL). The organicphasewasseparated and the aqueousphase wasextractedfurther with two 2-mL portionsof diethyl ether. The organiclayerswere combined,washed with brine (5.0 mL), dried (MgSO,) and concentratedunderreducedpressure.The resultingviscousbeige residuewaspurified by flashchromatographyon silicagel (20% ethyl acetate-hexane for elution) to give 317 mg (42%) of 6e asa white crystallinesolid: mp 97.3-99.9 “C; ‘H NMR (300 MHz, CDCl,) 6 7.50 (dd, J = 8.9, 13.6Hz, 2H, Ar-H), 6.76 (br s, 4H, Ar-H), 6.39 (dq, J = 6.5 Hz, JHep= 376 Hz, IH, P-H), 3.79 (s, 6H, OCH,), 2.28 (s, 6H, CH,), 1.54-0.38(br envelope,3H, BH,); “C NMR (75 MHz, CDCl,, ‘H decoupled)6 162.3(C), 143.9 (c), 143.7(c), 135.8(CH), 135.6(clf), 117.1(CH), 117.0 (m, 111.8 (Cl-I), 111.6 (CH), 75.2 (C), 70.3 (Q, 55.2 (CH,), 21.1 ((X-I,); ,]I’ NMR (202 MHz, CDCI,) 6 -17.0 (d, JP-H= 415 Hz); IR (film) 2358, 1599, 1564, 1489, 1455, 1303, 1242, 1079cm-‘; high resolutionmass spectrumc&d. for C&,,O,P (I&-BH,) 274.1124,found 274.1122. (2S,SS)-2,SHexanediol(8). The title compoundwaspreparedfrom acetonylacetone(5.71 g, 50.0 mmol, 1 e@iv) accordingto the methodof Lieser.“’ The mixture wasfiltered throughc&e andthe solidswererinsedwith four 50-mL portionsof ethyl acetate. The organicportion of the filtrate was separated and the aqueouslayer wassubjectedto continuousextraction with ethyl acetatefor 3 days. The combinedorganicextractswere dried (MgSO,) andconcentratedunderreducedpressureto yield a viscous beigeoil. Purification of this materialwasaccomplished by columnchromatographyon silicagel (ethyl acetatefor elution) to yield 4.49 g (75%) of 8 asa white solid. Recrystallizationfrom r-butyl-methyl ether afforded3.96 g (67%) of 8 as a white crystallinesolid: mp 50.4-53.2 “C; [a];’ + 35.2” (~~14.7, CHCl,), lit 21b[a]? + 34.9” (c=9.48, CHC13);‘H NMR (300 MHz, CDCl,) 8 3.78 (m, 2H, CH), 3.15 (br s, 2H, Oh), 1.53 (m, 4H, CHJ, 1.17 (d, J = 6.2 HZ, 6H, CH,); “C NMR (75 MHZ, CDCI,, ‘H decoupled) 6 68.1 (CH), 35.9 (CHJ, 23.6 (CH,). (2S,SS)-2,SHexanedioldi-p-toluenesulfonate(la). An oven-dried,round-bottomedflaskequipped with a rubberseptumanda magneticstirring bar waschargedwith (2S,SS)-2,5-hexanediol (1.18 g, 10.0mmol, 1 equiv), dichloromethane (30 mL) andpyridine (1.58 g, 20.0 mmol, 2 equiv). The solution wascooledto 0 “C andthenp-toluenesulfonylchloride (3.80 g, 20.0 mmol, 2 equiv) wasaddedin several smallportionsover a periodof 1 h. The mixture wasstirredat 0 “C for an additional19 h. The resulting white suspension wasdilutedwith dichloromethane (15 mL) andpartitionedbetween 10%aqueous hydrochloricacid solution(10 mL) anddichloromethane (5 mL). The organiclayer wasseparatedand the aqueouslayer wasextractedfurther with two lo-mL portionsof dichloromethane.The combinedorganic layerswerewashedwith another lo-mL portion of 10%aqueoushydrochloric acid solution,two 10-mL portionsof saturatedaqueoussodiumbicarbonatesolutionand dried ma,SO,). The solventswereevaporated underreducedpressureandthe resultingwhite solidwaspurified by recrystallizationfrom 10%heptanein methylcyclohexaneto yield 3.54 g (83%) of la asa white crystallinesolid: mp 94.5-97.0 “C; ‘H NMR (300MHz, CDCI,) 8 7.75 (d, J = 8.2 Hz, 4H, Ar-H), 7.32 (d, J = 8.2 Hz, 4H, Ar-H), 4.50 (m, 2H, CH), 2.43 (s, 6H, Ar-CH,), 1.54(m, 4H, CHJ, 1.11 (d, J = 6.3 Hz, 6H, CH,); “C NMR (75 MHz, CDCl,, ‘H decoupled)6 144.6(CJ, 134.8(CJ, 129.8(CI-I), 127.7(CH), 79.0 (c’H), 31.7 (CH,), 21.6 (GI,), 20.8 (CE,); XR(KBr) 3004,2980,2954,2930, 1598, 1450, 1438, 1378, 1323, 1308, 1294, 1189, 1171, 1096, 892, 852, 820, 758, 688, 578, 544, 522cm-‘. (lS,2S)-1,2-Bis[(diphenylphosphino)metbyl]cyclohexan~~P’-hexahydrodiboron (2a). An oven-driedroundbottomedflask equippedwith a magneticstirring bar waschargedwith (diphenylphosphine)trihydroboron (6b) (0.928 g, 4.64 mmol,2.1 equiv) andpurgedwith argon. The
C-Chiral bisphosphines
7663
reactionmixture wascooledto -78 “C and n-butyllithium (1.07 mL of a 4.50 M solutionin heptane,4.68 mmol,2.12 equiv) wasaddeddropwisevia syringeover a periodof 10 minutes. The reactiOnmixture waJ stirredat -78 “C for an additional10 minutesandthenwarmedto 25 “C for 10 min. The reaction mixture wasthencooledIO-40 “C and a solutionof (lS,2s)-1,2-di@-tosyloxymethyl)cyclohexaneD (1.00 g, 2.21 mmol, 1 equiv) in N,N-dimethylformamide(9.2 n&) wasaddedslowly via syringe. Uponcompletionof the addition, the mixture waswarmedslowly to 25 “C andstirredfor an additional9 h. The mixture was partitionedbetweendiethyl ether (20 mL) and 10%aqueoushydrochloric acid solution(25 mL). The organic layer wasseparated and the aqueouslayer wasextractedfurther with two 20 mL portionsof diethyl ether. The organiclayerswere combined,washedwith two 20 mL portionsof water andone20 mL portion of brine, dried (@SO,) andconcentratedin vacua. The resultingcolorlessresiduewaspurified by flash chromatographyon silica gel (40% ethyl acetate-hexanes for eiution) to yield 1.02 g (93%) of 2a a~a colorlesssolid. mp 184-189“C [CL]: + 15.6 “(C 0.027, CHCl,) ‘H NMR (75 MHz, CDCI,) 6 0.5-1.6 (br envelope,16H, Cy-H, CH, and BH,); 1.85 (ddd, 2H, J=14.2, 7.1, 6.7, P-CHEI); 2.19 (appt, 2H, P-Cl-W'); 7.26-7.47 (m, 12H, ArH); 7.54-7.60 (m, 4H, ArEI); 7.65-7.71 (m, 4H, ArH); “C m (300 MHz, CDCl,, ‘Hdecaupled)6 25.4, 29.5,29.9, 34.7, 38.3,38.4, 128.7, 128.8, 130.2, 130.3, 130.9, 131.0, 131.2, 132.1, 132.2, 132.4, 132.5; “P NMR (202, CDCl,) 6 13.96(S); IR (Ccl,) 3080, 3061, 3026, 3010,2932,2856.2384,2344,2254, 1958,1895,1814,1736, 1485, 1437, 1408, 1261, 1186, 1131, 1108, 1060,1028, 1000,958, 909, 866; high resolutionmassspectrumcalcd for &H,,PB, (I@-BHJ 493.4293, found493.4290. (1S,2S)-1,2-Bis[(dicyclohexylphosphino)methylleye~ (2b). The reactionof the lithium derivative of (dicyclohexylphosphine)trihydrobvron (6a) (56.1 mg, 0.263 mmd, 2.1 equiv) with ( l&25’)-1,2-di(p-tosyloxymethyl)cyclohexaneZ (56.5 mg, 0.125 mmol, 1 e@v) in tetrahydrofuran(2.0 mL) wascarriedout asdescribedfor 2e. After the describedworkup, evaporationof the solventsunderreducedpressureyielded 59.2 mg (89%) of 2h asa white residue. Purification by recrystallizationfrom heptaneaffordeda white crystallinesolid: mp 93.6-96.2 ‘C; [a]:: +10.7” (C = 0.06, CHCl,); ‘H Nh4R (300MHz, CDCL,)6 2.00-1.46 (br envelope,34H, Cy-H andCHJ, 1.45-1.00 @r envelope,28H, Cy-H andCH& 0.90-0.40 @r envelope,6H, BH,); “C NvfR (75 MHz, CD% ‘H decoupled)6 38.7, 38.6, 33.9, 33.2, 33.1, 32.7, 32.6, 27.8, 27.1, 27.0, 26.9, 26.6, 26.1, 25.8,24.9, 23.8, 23.4; 3’PNh4R(202 MHz, CDCl,) 1525.8 (s); IR (film) 2927, 2853, 2372, 1447, 1063cm-‘; high resolution massspectrumcalcd. for C,,H&P,(M+-BH,) 517.4293,found 517.4248. (2R,4R)-2,~Bis(dicyclohexylphosphino)pentane-P:P’-hexahydrodihoron(2~). An oven-dried, round-bottomedflask equippedwith a magnetic&ring bar anda rubber septumwaschargedwith (dicyclohexylphosphine)trihydroboron (6a) (54.7 mg, 0.263 mmol, 2.1 equiv), tetiydrofulan (0.5 mL) and purgedwith argon. Upon coolingto -78 ‘C, n-butyllithium (40.3 pL of a 7.17 M solutionin heptane, 0.289 mmol, 2.3 equiv) wasaddeddropwisevia syringeover a periodof 10 min, followedby the additionof hexamethyiphosphorictriamide(0.5 mL) to the reactionflask. The mixture wasstirredat -78 “C for 30 min then warmedto 0 “C for 20 min. After coolingto -40 “C, a solutionof (2S,4J3-2,4-pentanediol dip-toluenesulfonate p (51.5 mg, 0.125 mmol, 1 equiv) in NJ-dimethylformamide (0.5 mL) wasadded drapwisevia syringe. Upon completionof the addition, the mixture waswarmedslowly lo 25 “C and shxd for an additional3 h. The mixture waspartitionedbetweendiethyl ether (1.0 mL) and 10%aqueoushydrochloric acid solution(1.5 mL). The organiclayer wasseparated and the aqueouslayer wasextractedfurther with four I-mL portionsof diethyl ether. The organiclayerswere combined,washedwith tW02-n’& portionsof water andone 2-mL portion of brine, dried (MgSO,) andconcentratedin vacua. The resulting beigeresiduewaspurified by flashcolumnchromatographyon silica gel (10% ethyl acetate-hexane for elution)andthe materialthat wasobtined in this way wasrecryt&iz& from hexaneat 0 “C to yield 58 mg (91%) of 2c asa white solid: mp 92.1-94.6 “C; [a]; - 11.4” (c = 0.06, CHCI,); ‘H NMR (300 MHz, CDCl,) 6 2.04-1.57 @renvelope,24H, CH and Cy-H), 1.50-1.12 (br envelope,24H, CH, ad Cy-Hh 1.14 (dd, J = 7.1, 13.4 HZ, 6H, CH,), 1.01--0.20 (br envelope,6H, BH,); ‘T NMR (75 MHZ, CDCl,, ‘H decoupled)8 34.9, 34.5, 26.5, 26.4, 25.9, 25.7, 24.8, 22.3, 13.9; 3’p N&~R(202MHz, CDCI,) 8 24.1 (s);
7664
L. MCKINSTRYandT. LIVINGHOUSE
IR (film) 2929, 2852, 2365, 1449,889 cm-‘; high resolutionmassspectrumcalcd. for CJ-I,,BP,(M+-BH,) 477.3950,found477.3949. (2R,5R)-2,5-Bis(dicyclohexylphosphino)hexaoe-P:P1-hexahydrodiboron (2d). The reactionof the lithium derivative of (dicyclohexylphosphine)trihydroboron (6a) (112 mg, 0.525 mmol, 2.1 equiv) with la (107 mg, 0.250 mmol, 1 equiv) wascarriedout asdescribedfor 2e. After the describedworkup, evaporationof the solventsunderreducedpressureyielded a white solid. This materialwaspurified by crystallizationfrom 10%ethyl acetatein hexanesto yield 107mg (86%) of 2d asa white crystallinesolid: mp 203.2-205.4“C; [a]: - 19.5” (c = 0.01, CHClJ; ‘H NMR (300 MHz, CDCI,) 6 1.95-1.60(m, 35H, Cy-H envelope),1.55-1.20(m, 15H, CH, CH, andCy-H envelope), 1.17 (dd, J = 7.0, 13.3 Hz, 6H, CHJ, 0.77--2.30 (br envelope,6H, BH,); 13CNMR (75 MHz, CDCI,, ‘H decoupled)6 31.6, 31.5, 31.2, 31.1, 30.5, 30.4, 28.2, 27.9, 27.8, 27.7, 27.3, 27.2, 26.1, 25.4, 25.0, 14.6; ‘iP NMR (202 MHz, CDC13)8 31.1 (br s); IR (film) 2927, 2853, 2362, 2342, 1067cm-i; high resolutionmassspectrumcalcd. for C,JIJ3P,(M+-BH,) 492.4185,found 492.4210. (2R,SR)-2,5-Bis(diphenylph~p~o)hexan~~P’-hex~y~o~bo~n (2e). An oven-dried,roundbottomedflaskequippedwith a magneticstirring bar anda rubberseptumwaschargedwith (diphenylphosphine)trihydroboron (6b) (100 mg, 0.50 mmol, 2.1 equiv), tetrahydrofuran(1.5 mL) and purgedwith argon. Uponcooling to -78 “C, n-butyllithium (88.0 PL of a 5.80 M solutionin heptane, 0.5 1 mmol, 2.12 equiv) wasaddeddropwisevia syringeover a period of 10 min. The reactionmixture was stirredat -78 “C for an additional10 min andthenwarmedto 25 “C for 10 min. Upon coolingto -40 “C, a solutionof la (102 mg, 0.24 mmol, 1 equiv) in N,N-dimethylformamide(1.O mL) wasaddedslowly via syringe. Upon completionof the addition,the mixture waswarmedslowly to 25 “C andstirredfor an additional9 h. The mixture waspartitionedbetweendiethyl ether (2.0 mL) and 10%aqueoushydrochloric acid solution(3.0 mL). The organiclayer wasseparated andthe aqueouslayer wasextractedfurther with four 2-mL portionsof diethyl ether. The organiclayerswerecombined,washedwith two 2-mL portionsof waterandone2-mL portion of brine, dried (MgSO,) andconcentratedin vacua. T’heresultingbeigeresidue waspurified by flashcolumnchromatographyon silicagel (20% ethyl acetate-hexane for elution) to yield 102mg (88%) of 2e asa white solid: mp 153.4-154.8“C; [a]; + 35.2” (c= 14.7, CHCI,), lit.2lb [a]3 -9.5“ (c = 0.01, CHCl,); ‘H NMR (300 MHz, CDCI,) 6 7.68-7.62 (m, 8H, Ph-H), 7.47-7.36 (m, 12H, Ph-H), 2.37 (appSept.,J = 7.4 Hz, 2H, CH), 1.52 (m, 4H, CHJ, 1.01 (dd, J = 6.9, 16.5 Hz, 6H, CH,), 1.45-0.20(br envelope,6H, BH,); “C NMR (75 MHZ, CDCI,, ‘H decoupled)6 132.7(CH), 132.6(CH), 132.5(C’H), 132.4(CID, 131.1 (CH), 128.9(c), 128.8(C’H), 128.7 (CH), 128.6(CH), 128.3(c), 29.5 (CH), 29.4 (CH), 28.7 (CH2), 28.2 (CHJ, 13.7 (CH,); 31PNMR (202 MHZ, CDCI,) 6 23.9 (s); IR (film) 2928, 2385, 1436, 1107, 1064cm-‘; high resolutionmassspectrumcalcd. for C3&13,P,(M+-B&) 454.1982, found 454.1980. (2R,2R)-2,5-Bis[bis(4-methoxy-2-methylphenyI)phosphino]hexane-P:P’-hexahydrodiboron (2f). The reactionof the lithium derivative of [bis(4-methoxy-2-methylphenyl)phosphine]trihydroboron (SC) (154 mg, 0.525 mmol, 2.1 equiv) with la (107 mg, 0.250 mmol, 1 equiv) wascarriedout asdescribedfor 2e. After the describedworkup, evaporationof the solventsunderreducedpressureyielded a white solid. This materialwaspurified by crystallizationfrom methylcyclohexaneto yield 135mg (82%) of 2f asa white crystallinesolid: mp 149.3-153.1“C; [a]P -20.4“ (c = 0.02, CHCl,); ‘H NMR (300 MHz, CDCl,) 6 7.77 (dd, J = 11.5, 10.5Hz, 2H, Ar?H), 7.49 (appt, J = 10.5Hz, 2H, Ar-H), 6.77 (appd, J = 8.5 Hz, 4H, Ar-H), 6.66 (appd, J = 17.2 Hz, 4H, Ar-H), 3.81 (s, 6H, OCH,), 3.79 (s, 6H, OCH,), 2.54 (m, 2H, CH), 2.08 (s, 6H, CH,), 1.99 (s, 6H, CH,), 1.76 (m, 4H, CHJ, 1.07 (dd, J = 6.8, 16.5 Hz, 6H, CH,), 1.902 (br envelope,6H, BH,); 13CNMR (75 MHz, CDCl,, ‘H decoupled)6 161.7, 161.0, 144.7, 144.2, 135.8, 135.3, 134.1, 133.6, 129.7, 127.6, 117.6, 111.1,79.5, 55.0, 28.1, 27.7, 21.7, 20.3, 14.4; “PNMR (202 MHz, CDCI,) 6 21.4 (s); IR (film) 2933, 2383, 1598, 1565, 1489, 1464, 1302, 1237, 1075 cm-‘; high resolutionmassspectrumcalcd. for C,,H.,,O,P,(M+-%Hd 630.3030,found 630.3028.
C-Chiral bisphosphines
7665
Preparation of Biiphosphine Ligands 3d-f. Representative Procedure for PhosphineBomne Decomplexation with HBF,*OMep: (ZR,!X)-2,5-Bi(diphenylphosphino)hexane (3e). A flame-dried test tube (16 mm x 100 mm) equipped with a stirring bar and a rubber septum was charged with 2e (48.2 mg, 0.10 mmol, 1 equiv), dichloromethane (1.0 mL) and purged with argon. Upon cooling to -5 “C, tetrafluoroboric acid dimethyl ether complex (134 mg, 1.00 mmol, 10.0 equiv) was added dropwise by syringe. An exothermic reaction ensued and gas evolved. The reaction mixture was then’warmed to 25 “C and stirred for an additional 12 h. Subsequently, the mixture was diluted with degassed, anhydrous diethyl ether (2.0 mL) and added to degas&, saturated aqueous sodium bicarbonate solution (5.0 mL) contained in a small Erlenmeyer flask. The resulting biphasic mixture was stirred vigorously under argon for 10 min and thenpouredinto a separatoryfunnel. The organiclayer wasseparated andthe aqueouslayer wasexbacti (WI&Y argon) with two 2-mL portionsof degassed, anhydrousdiethyl ether. The organiclayerswere combined,washedwith two 3-mL portionsof degassed water andone3-mL portion of brine, dried (MgSO,) (all un&r argon) andconcentratedin vacua. The resultingwhite solidwasrecrystallizedfrom degassed methylcyclohexaneat 0 “C to give 45.3 mg (99%) of 3e asa white crystallinesolid: mp 179.3-183.6“C; [[I]~~ f7.0” (c = 1.0, CHCl,); ‘H NMR (300 MHz, CDC&) 6 7.67 (m, 8H, Ar-H), 7.55-7.38 (m, 12H, k-H), 2.25 (m, ZH, CH), 1.61 (m, 4H, CH3, 1.03 (dd, J = 7.1, 17.0 Hz, 6H, CH,); 13CNMR (75 MHZ, CDCl,, ‘H decoupled)131.4, 130.9, 128.4, 32.8, 32.1, 27.6, 11.9; 3’P NMR (202 MHz, CDCI,) 6 -1.8 (s); IR (KBr) 3068, 3052, 2956, 2930,2880, 2852, 1480, 1458, 1432, 1376, 1196, 1092, 1068, 1026,738, 696, 658, 510 cm-‘; high resolutionmassspectrumc&d. for C&32P,(M+) 454.1982,found 454.1979. (2R,4%2,4-Bii(dicyclohexylphosphino)peutane (3~): white solid; yield (91%); mp 182.3-184.9“C; ‘H NMR (300MHz, CDCl,) 6 2.03 (m, 2H, CH), 1.95-l .64 (m, 22H, Cy-H envelope),1.53 (s, 2H, CH& l-47-1.15 (m, 22H, Cy-H envelope),1.15 (dd, J = 7.1, 13.3 Hz, 6H, CH,); ‘%I NMR (75 MHz, CDCI,, ‘Hdecoupled)6 31.8, 31.1, 30.0, 28.1, 27.8, 27.5, 27.3, 27.2, 26.0, 25.4, 25.0, 15.8; “PNMR (202 MHz, C$J 6 6.5 (s); high resolutionmassspectrumcalcd. for C&,P,(M+) 464.3704,found 464.3700. (2R,SR)-2,5-Rk(dicyclohexyIphosphino)hexane(3d): white solid; yield (91%); mp 184.6-187.3“C; ‘H NMR (300 MHz, CDCI,) 6 1.96-1.60(m, 35H, Cy-H envelope), 1.60-1.05(m, 15H, CH, CH, andCyH envelope),1.16 (dd, I = 7.2, 16.1 Hz, 6H, CH,); “C Nh4R (75 MHz, CDCI,, ‘H decoupled)6 35.9, 35.1, 30.2, 29.4, 28.7, 28.5, 27.0, 26.9, 26.8, 26.6, 26.5, 26.3, 26.1, 13.3; “P NMR (202 MHz, CDCl,) 8 11.1 (s); IR (film) 2929, 2852, 1449, 1157cm-‘; high resolutionmassspectrumcalcd. for C,&,P,(M+-H) 477.3783, found477.3780. (2R,SR)-2,5-Bis[bis(emethoxy-2-methylphenyl)phosphino]hexane (32): white solid; yield (96%); mp 178.4-181.9“C; ‘H NMR (300 MHz, CDC13)6 7.17-7.08 (m, 4H, Ar-H), 6.71-6.63 (m, 8H, Ar-H), 3.78 6, 6H, OCH,), 3.74 (s, 6H, OCH,), 2.44 (s, 6H, CH,), 2.37 (s, 6H, CH,), 2.10 (m, 2H, CH), 1.47 (m, 4H, CHJ, 0.89 (dd, J = 6.8, 16.0 HZ, 6H, CH,); 13CNMR (75 MHZ, c~cl,, ‘H decoupled)6 159.7, 144.8, 144.6, 133.2, 132.5, 115.7, 115.6, 111.7, 54.9, 52.0, 31.5, 30.5, 29.6, 21.4, 16.1, 15.8; 3’PNMR (202 MHz, CDC13)6 -32.4 (s); IR (film) 2925, 2852, 1595, 1564, 1483, 1464, 1296, 1238, 1071cm-‘; high resolutionmassspectrumc&d. for C,,H,,O,P,(M+) 630.3030,found 630.3028.
LITERATURE CITED AND FOOTNOTES 1. 2. 3. 4.
Fellow of the Alexander von HumboldtFoundation1993-1995. Noyori, R. AsymmetricCatalysisin OrganicSymhesis.JohnWiley andSons: New York, 1994. Pietrusiewicz,K. M.; Zablocka,M. them. Rev. 1994,94, 1375. For a review see: Kagan, H. B.; Sas&i, M. In TheChemistryof Organophosphorus COmpOUndr; Hartley, F. R., Ed.; Wiley: New York, 1990;vol. 1, p. 51.
7666
5.
6. 7. 8. 9. 10. 11. 12. 13. 14.
15.
16. 17. 18. 19. 20. 21. 22. 23. 24. 25.
L.
MCKINSTRY
and T. LIVINGHOUSE
a) Kagan, H. B.; Dang, T. -P. J. Am, Chem.Sot. 1972,94, 6429. b) Dang, T. -P.; Poulin, J. C.; Kagan, H. B. J. Organomet. Chem. 1975, 91, 105. c) Morimoto, T.; Chiba, M.; Achiwa, K. Chem.Ph. Bull. 1992,40, 2894and referencescited therein. d) Inoguchi, K.; Fujie, N.; Yoshikawa,K.; Achiwa, K. Chem.Pharm. Bull. 1992, 40, 2921and referencescited therein. e) McNeil, P. A.; Roberts,N. K.; Bosnich,B. J. Am. Chem.Sot. 1981, 103, 2273. f) Fryzuk, M. D.; Bosnich,B. J. Am. Chem.Sot. 1977, 99, 6262. g) Hobbs,C. F.; Knowles, W. S. J. Org. Chem. 1981, 46, 4422 and referencescited therein. h) Hayashi,T.; Tanaka, M.; Ogata, I. J. Mol. Cuful. 1984,26, 17. i) Ojima, I.; Kogure, T. C&m. Lett. 1979, 641. j) Nagel, U. Angew. Chem.ht. Ed. Engl. 1984, 23, 435. k) Bakos,J. ; Toth, I.; Heil, B.; Marko, L. J. Organomet.Chem. 1985,279, 23. 1) Kagan,H. B.; Fiaud, J. C.; Hoomaert, F. C.; Meyer, D.; Poulin, J. C. Bull. Sot. Chim.Belg. 1979, 88, 923. In selectedinstances,eliminationhasbeenminimizedby the useof cyclic sulfatesassubstrates in displacementreactionswhich employan unhinderedlithium phosphideasa nuclephile: Burk, M. J. J. Am. Chem.Sot. 1991,113, 8518. Tani, K.; Suwa, K.; Yamagata,T.; Otsuka,S. Gem. Len. 1982,265. a) Imamoto, T. PureAppl. Ckm. 1993, 65, 655 andreferencestherein. b) Imamoto,T.; Oshiki, T.; Onozawa,T.; Kusumoto,T.; Sato, K. J. Am. Chem. Sot. 1990,112, 5244. a) During the courseof this work a singleexamplewasreportedin which the lithium derivative of diphenylphosphine-borane wasusedto synthesize. DIOP.9b b) B&et, H.; Gourdel, Y.; Pellon, P.; Le Corre, M. TetrahedronLen. 1993,34, 4523. McKinstry, L.; Livinghouse,T. TetrahedronL&t. 1994, 35, 9319. The useof old, alkoxidecontaminatedsamples of n-BuLi for this purposeresultsin greatly diminishedyieldsof the desiredsubstitutionproducts2a-f. Diastereomericpurity for 2a-f wasinferred by high field ‘H and “C NMR analysiswhich indicated the absenceof mesoisomers.In addition, 2a-f were homogeneous by HPLC and GLC. All new phosphine-borane complexeswerefully characterizedby ‘H, 13Cand “P NMR, IR and possessed satisfactorycombustionanalysesor exactmass. Severalalternative setsof conditionsintendedfor boranedecomplexationwere examinedandfound to be ineffective. Theseincluded: exposureof 2i to EtO-K+ in PhMe or THF; treatmentwith 18crown-6*K+CN- in Et$IH; andwarmingin the presenceof “catalytic” (10 mol %) (n-B&P in morpholine. A transientcompound[presumablythe monoboranecomplexDPPE*(BH,) (lo)] was observedat intermediatestagesof the reaction. An authenticsampleof 10 wasprepared(albeitwith poor selectivity) by the exposureof 3i (1.2 equiv) to BH,*SMe, (1.Oequiv) followed by chromatographic purification. As a moreeconomicalalternative,boranedecomplexationcould be readily effected (e.g., 25 “C, 4 h) by treatmentwith preformedHBF,vOEt, [BF,*OEtr (1 equiv) + I-IF& (1 equiv)]. Ether complexesof BF, and HBF, wereobtainedfrom Aldrich ChemicalCo. In contrast, the 1,3dioxolanelinkagepresentwithin the bisboranederivative of DIOP wasdegraded underthe prescribedsetof reactionconditions. Still, W. C.; Kahn, M.; Mitra, A. J. Org. C&m. 1978, 43, 2933. 4-Bromo-3-methylanisole waspreparedaccordingto a literatureprocedure: Oshiki, T.; Imamoto,T. Bull. Chem.Sot. Jpn. 1990, 63, 3719. Noth, H.; Vetter, H. -J. ~Chem.Ber. 1963, 96, 1109. a) Lieser, J. K. Synfh. Commun.1983, 13a, 765. b) Short, R. P.; Kennedy, R. M.; Masamune,S. J. Org. #em. 1989,54, 1755. The requisiteditosylate9 waspreparedfrom (2S,4S)-2,4-dihydroxypentane by treatmentwith p-toluenesulfonylchloridein the presenceof pyridine (vi& supra). Preparedand characterizedby Mr. D. J. Sheehanof theselaboratories. Analogousdecomplexationof 2a2’ on a 1 mmolscaleprovided3a in 97% isolatedyield. Preparedon a 2.21 mm01scalein 93%yield by Mr. D. Belangerof theselaboratories.
(Received in USA 22 December 1994; accepted 9 May 1995)
Tetrahedron
Pergamon
0040.4020/95
$9.50+0.00
0040-4020(95)00390-8
An Effkient
Procedure
for the Synthesis of C-Chiral
Lydia McKiiry
Bisphosphines.
and Tom Livinghouse”
Departmentof Chemistry and Biochemistry Montana StateUniversity Bozeman, MT 59717 U.S.A.
Abstract: A practical method for the synthesisof bisphosphks containing homochiml carbon backbonesis described. This procedure entails sequential reaction of a homochkal ditosylate with the appropriate dialkyl- or dkylphosphine-bon anion followed by BH, decomplexation mediatedby HBF,.OM+
Homochiralphosphines that form stereodifferentiated chelatecomplexeswith transitionmetalshave becomeindispensable tools for asymmetriccatalysis2 At the presenttime there is a noteworthy deficiency of general methodsfor the enantioselective synthesisof P-chiral phosphines.’In consequence, the largest
existingfamily of phosphines that havebeendevelopedfor asymmetriccatalysiscomprisesmoleculesin which stericdifferentiationat phosphorus is impartedby homochiralcarbonbackbones4The most commonlyutilized procedurefor the synthesisof manyof thesephosphines involves the alkylation of strong& basic diary1or dialkyl metallophosphides with the appropriatehomochiraldisulfonate.’ Unfortunately, this
methodis not alwaysreliablein that diminishedyieldsof the desiredsubstitutionproductcanresult asa consequence of competingsidereactionssuchas basemediated elimination,
electrontransferprocesses, etc.
Interveningreactionsof this variety are particularlyproblematicwhenvery basicmetalloderivativesof stericallyhindereddialkyl phosphines are usedasnucleophiles.For thesespecies,efficient carbonphosphorus bond formationis mosteffectively achievedby usinga homochiraldzjluorideas the substrate.6’7 Over the pastfew years, Imamotoandco-workershavepublisheda seriesof importantpaperson the syntheticutility of phosphine-borane complexes.’The nucleophilicbut mikiiy basic anionsderived from secondaryphosphine-boranes havebeenshownto undergoalkylation, 1,4-additionandPd(0) catalyzedcrosscouplingreactionswith a wide variety of commonsubstrates. 8 It is thereforesurprisingthat the potential utility of thesecomplexesfor the synthesisof bisphosphines containinghomochiralcarbon backboneshas beenlargely overlooked.’ We havepreviously communicated a versatilemethodfor the synthesisof C-chiral bisphosphines that relieson the alkylation of phosphine-borane anionswith homochiralditosylates.” Herein we provide a moredetailedaccountof this method. 7655
L. MCKINSTRY and T. LIVINGHOUSE
7656
The generalprocedurethat wasroutinely employedfor the synthesisof C-chiralbisphosphine-borane intermediates involvesthe deprotonationof the requisitemonophosphine-borane adductsbusing“alkoxide free” n-BuLi” (THF, -78 “C) followedby the additionof a DMF solutionof the homochiralditosylateof interest(-40 “C). Typically, the reactionmixture is thenstirred underargonat ambienttemperatureuntil complexesthat have been bis-alkylationhasbeenachieved(Scheme1).“9” A seriesof bisphosphine-borane synthesizedin this manneris shownin Table I. The preparativegeneralityof the aboveprocedurecan be inferred from the high yields obtainedfor the u,cr’-branchedcyclohexyl bearingbisphosphine-boranes 2d and 2c aswell asfor the stericallycongestedbis(diarylphosphine-borane) analog2f.
r \
-BHo \
OTs (RhP-BH3’
p+w2
u+ (
DMF - lHF
=
OTs
)”
(eql)
t
P+(R)2 I
4)
-BHB
(n=1,2) 1
Table I.
2
Synthesisof Representative Bisphosphine-boranes via NucleophilicDisplacementwith Phosphine-borane Anions.
2a ( 93 %)
2b ( 89 %)
HtB
2d ( 86 %)
-BH3
2e ( 88 %) ( Ar = 2-CH&(CH30)C&
1
7651
C-Chiral bisphosphines
The reported procedures for converting phosphine-boranes to the corresponding free phosphines involve heating the parent complexes with a large excess of a secondary amine (e.g., morpholine or diethyl amine)ab or DABCO. 9b Although 2e could be converted to bisphosphine 3e by either of the published procedures, the bisborane complexes 2b, 2c and 2d proved remarkablyresistanttoward aminemediatedBH, exchange. Even at elevatedtemperatures(e.g., 100 “C), thesecomplexeswere incompletelyconverted(-70-80%) to the correspondingbisphosphines.An examinationof other boraneadductsof hindered,electronrich phosphines further indicatedthat BH, decomplexationby amineexchangecart be an inefficient process. Presumably,the enhancedstrengthof the P-B bondin boranecomplexesof electronrich phosphines is responsiblefor the observedlethargy of 2b, k,
2d andother hinderedBH, adductstoward aminolysis. In light of this apparent
limitation, we setout to developan alternativeandcomplementarymethodfor phosphine-borane decomplexation.‘4Imamotohasrepoti
that representativesulfonicacidsreact with phosphine-boranes in
aproticmediato provide the correspondingboranesulfonatederivatives.*’ In a preliminary study to determineif this type of reactioncould serveasa basisfor phosphinedeprotection,DPPfi(BH,), (2i) was treatedwith a variety of acids(i.e., CH,SO,H, CF,SO,H, HBF,*OMq, etc., CHJI,, -5 “C - 25 “C) and subsequently hydrolyzed WaHCO, aq., 0 “C (10 min underAr) or K,CO, a&z., 25 “C (6.5 h underAr)]. A roughmeasureof the efficiency of decomplexationwasobtainedby TLC analysesof reactionaliquots. This procedurereadily mmkd
the stepwiseconversionof 2i to DPPE (3i) (Scheme2).15 Of the various
acids
that wereexamined,commercialHBF,*OM% proved the mostefficaciousin termsof rate aswell asisolated yield of free phosphine.16 Although reactionconditionscustomtailoredto a given phosphine-borane couldbe readily derived, thestandard conditionsthat were usedfor ail of the examplesdescribedhereinvolve treatmentwith HBF,*OMe, [(S equiv/P*BH, moiety), CH,Cl,, -5 “c - 25 “C, 12 h] followed by hydrolysis (NaHCOr~q., 0 “C). The resultsobtainedfor the decomplexationof a rangeof phosphine-boranes are illustratedin Table II.
n P+P), (PM’* I I H$ -B&j
21
a)
HBF,DMq *
b)
NaHCO, of KzC4
(a$) (an/~.) 31
7658
L. MCKINSTRY
Table II.
and T. LIVINGHOUSE
HBF,*OMe, Mediated Decomplexation of Representative Bisphosphine-boranes.
3a (97%)
3c (91%)
3j (98%)
3f (98%) [ Ar = 2-CH,4(CH,0)C6HJ
Me,
,Me S1
eP(Ph),
(‘1 PW
W’hh
W’hh
3g (89
1
%)
WW
/(Ph)
2
31 (92%)
3h (94%)
To gain insight into the prospective mechanism of decomplexation, methyldiphenylphosphine-borane (4) was treated with HBF,*OMe, (1 quiv) in CDCI,.
‘H
NMR
analysis revealed consumption of 4 with
concomitant formation of a product possessing a down field shifted methyl doublet of doublets at 2.41 ppm (Jn.r = 15.22 Hz and J+,-r = 5.82 Hz). In addition, “P NMR analysis revealed an up field shifted signal at 1.98 ppm (doublet of multiplets, .I,, = 521 Hz). The appearance of these new resonances is consistent with the intermediacy of the phosphine-fluoroborane complex 5 (eq 3).
-BH, I Ph)Z+P,CH
HBF;OMe,
(eq3) 3
C-Chiral bisphosphines
7659
As is evident from the examples presented above, the HBF,*OMe, decomplexation procedure can facilitate rapid access to certain electron rich homochiral bisphosphines that are otherwise very difficult to prepare. In addition, the conditions for decomplexation are sufficiently mild to permit the survival of the C-Si and ferrocenyl linkages of ligands 3g and 3h.17 It is also noteworthy that highly impure samples of valuable phosphines can be conveniently purified via the corresponding BH, adducts. For example, treatment of impure (lS,25’)-1,2-bis(diphenylphosphinomethyl)cyclohexane
(3a) (of 80% purity) with BH,rSM%
(2.1 equiv) followed by trituration with methanol gave the highly crystalline bisborane adduct. Decomplexation of this material in the usual manner returned pure 3a.
3a Contaminated bisphosphine
with IX. 20 % oxides
( > 99%
pure )
(eq4)
The efficient route to homochiral bisphosphine-boranes delineated here, when utilized in tandem with the convenient HBF,*OMe, decomplexation procedure, is expected to facilitate the preparation of a wide range of stereochemically varied phosphine ligands. The synthesis and utilization of these new chiral modifiers for asymmetric catalysis will be described in upcoming Acknowledgements.
accounts
from these laboratories.
Generous support for this research by grants from the National Institute of Health and
the National Science Foundation is gratefully acknowledged. EXPERIMENTAL General procedures.
SECTION
All reactions were performed in either oven-dried or flame-dried round- bottom
flasks fitted with rubber septa, under a positive pressure of argon, unless otherwise noted. Air- and moisture-sensitive liquids and solutions were transferred via syringe or stainless steel cannula. Organic solutions were concentrated by rotary evaporation at -25 Torr (water aspirator) with a Buchi rotary evaporator. Analytical gas chromatography was performed on a Varian Model 3700 Gas Chromatograph equipped with a flame ionization detector, a Hewlett-Packard 339oA reporting integrator and a
7660
L. MCKINSTRY
and T. LIVI~VGHOUSE
15 m X 0.54 mmID columnwith DB5 (or SE-45or equivalent)bondedphase. Preparativegas chromatographywasperformedon a Varian Model 3300 GasChromatographequippedwith a thermal conductivity detector,a Hewlett-Packard3390A reportingintegratoranda 1.8 m X 4 mmcolumnwith a 10%siliconeOV-17 chromosorbadsorbentphase.High PerformanceLiquid Chromatographywas performed
on an IBM LC/9533 Ternary GradientLiquid Chromatographequippedwith an IBM LC/9523
VariableW Detector. For generalanalyticalseparations an IBM 250 mm X 4.5 mmID columnpacked with IBM 5 pm sphericalsilicawasusedin conjunctionwith a Linear Model 156 chartrecorder. Flash columnchromatographywasperformedasdescribedby Still’B employingE. Merck 230-400ASTM mesh, 0.040-0.063mmparticle size, silicagel 60. Solvent systemsusedfor elutionare reportedin % volume/volume. Analytical thin-layer chromatographywasperformedusingK42-G platessuppliedby Alltech Associates. Materials. Commercialreagentsandsolventswereusedasreceivedwith the following exceptions. Tetrahydrofuran,1,2-dimethoxyethane,benzene,heptaneand hexanewere distilledfrom potassium.Diethyl etherwasdistilledfrom sodium-benzophenone ketyl. N,N-dimethylformamideandhexamethylphosphoric triamideweredistilledfrom calciumhydrideat 20Torr, while dichloromethane,acetonitrile,toluene and 2-butanolweredistilledfrom calciumhydrideat atmosphericpressureunderan inert atmosphere of argonor nitrogen. Purificationof methanolwasaccomplished by distillation from magnesium dimethoxideunderan atmosphere of argon. The molaritiesindicatedfor organolithiumreagentswere established by titration with a standardsolutionof 2-butanolin xylene using1,lo-phenanthrolineasindicator. Grignardreagentswere titrated in the samemanner. Periodicallythesereagentswere titrated for total basecontentwith a standard solutionof potassiumbiphthalateusingphenolphthalein asindicator. Instrumentation. Proton andcabon nuclearmagneticresonance(iH NMR and i3CNMR) spectra weremeasured at 300and 75 MHz, respectively,with a Bruker AC-300 spectrometer.Phosphorus nuclear magneticresonance (“P NMR) spectrawere measured at 202 MHz with a Bruker AM-500 spectrometer. Protonchemicalshiftsare reportedas6 valuesin partsper million down field from tetramethylsilaneandare referencedto residualprotium in the NMR solvent(CHCI,: 6 7.24, C,HD,: 6 7.15). Carbonchemical shiftsare reportedas6 valuesin partsper million down field from tetramethylsilane andare referencedto the 13Cin the NMR solvent(CDCI,: 6 77.0, C,D,: 6 128.0). Phosphorus chemicalshiftsare reportedas b values in partsper million down field from 85%aqueousphosphoricacid andare referencedinternally to the 3’Psignalin triphenyl phosphine(6 -6.0). Dataare representedasfollows: chemicalshift, multiplicity (s = singlet,d = doublet,t = triplet, q = quartet, m = multiplet), integration,couplingconstantin Hertz (Hz) andassignment.High resolutionmassspectrawere measured on a VG Analytical 7070Espectrometer by Dr. L. J. Sears. Infrared spectrawere recordedwith either a Bruker IFS 25 IR, a Perkin-Elmer1800 FTIR or a Perkin-Elmer237Bgrating IR. Melting pointswere determinedwith either a Fisher-Johns or a
C-Chiral bisphosphines
7661
Mel-Temp II melting point apparatus and are uncorrected. Optical rotations were measured with a PerkinElmer 241 C polarimeter. Elemental analysis was performed by Desert Analytics, Tucson, AZ. @icyclohexylphosphine)trihydroboron (6a). An oven-dried,round-bottomedflask fitted with a rubberseptumanda magneticstirringbar waschargedwith dicyclohexylphosphine(431 mg, 2.22 mmol, 1 equiv), diethyl ether (3.0 mL) andpurgedwith argon. The solutionwascooledto 0 “C, whereuponborane methyl sulfide(0.330 mL of a 10.1M solution,3.33 mmol, 1.5 equiv) wasaddedslowly by syringe. The reactionmixture waswarmedslowly to 25 “C andsubsequently stirredat this temperaturefor an additional 2 h. The solventswereevaporatedunderreducedpressureandthe resultingresiduewastriturated with three 2-mL portionsof diethyl ether to give 456 mg (99%) of 6a asa white solid: mp 78.6-80.9 “C; ‘H NMR (300 MHz, CDCl,) 6 4.11 (appd sx, J = 4.9 Hz, JH+ = 351 HZ, P-H), 1.80 (m, lOH, CHJ, 1.71 (br m, 2H, P-CH), 1.25 (m, lOH, CHJ, 0.40 (br q, JnB = 94.7 Hz, 3H, BH,); “C NMR (75 MHz, CDCl,, ‘H decoupled)6 29.4, 29.2, 28.8, 28.6, 27.7, 26.7, 26.5, 26.3, 25.7; 3’PNMR (202 MHz, CDCl,) 6 17.3 (br d, J,, = 351 Hz); IR (film) 2929,2853, 2382, 2350, 1449, 1062cm-i. Anal. Calcd. for C,,H,,BP: C, 67.93; H, 12.36; P, 14.61. Found: C, 68.14; H, 12.02; P, 14.50. (Diphenylphosphme)trihydroboron (6b). The reactionof diphenylphosphine (1.86 g, 10.0 mmol, 1 equiv) with boranemethyl sulfide(1.08 mL of a 10.2 M solution, 11.0 mmol, 1.1 equiv) wascarriedout asdescribedfor 6a. @iphenylphosphine)trihydroboron (6b) wasisolated(1.96 g, 98%) asa viscousclear oil: ‘H NMR (300 MHz, CDCl,) 6 7.68-7.61 (m, 2H, Ph-H), 7.50-7.41 (m, 8H, Ph-H), 6.29 (dq, J = 6.9 Hz, JHep= 378 Hz, lH, P-H), 1.07 (br q, JHe8= 97.3 Hz, 3H, BH,); “C NMR (75 MHz, CDC&, ‘H decoupled)6 133.1(CH), 132.9(CH), 131.6(CH), 129.2(CH), 129.0(CH), 128.5(c); “P NMR (202 MHz, CDCl,) 8 0.8 (d, JP.u= 337 Hz); IR (film) 2388, 1483,1438, 1109, 1059cm-‘. 4Lithio-3-methylanisole. An oven-dried,250 mL, three-necked,round-bottomedflask wasfitted with a pressureequalizingadditionfunnel, glassstopper,condenser,magneticstirring bar andglassbeads. The vesselwaspurgedwith argonandchargedwith diethyl ether(20 mL). The stopperwasremovedand replacedwith a conical funnelwhile a constantflow of argonwaspassedthrough the flask. Lithium wire, alloyedwith 1% sodium[0.385 g, 55.0 mmol, 2.2 equiv (prewashed with toluene)], washeld with forceps over the funneland cut with cleanscissorsinto 2 mmpiecessothat they droppeddirectly into the ether. A solutionof 4-bromo-3-methylanisole’9 (5.02 g, 25.0 mmol, 1 equiv) in diethyl ether (50 mL) wasadded slowly to the lithium suspension via additionfunnel, suchthat the reactionmixture wasmaintainedat reflux. Uponcompletionof the addition,the yellow solutionwasstirredvigorously at 25 “C for an additional3 h. Bis(4-methoxy-2-methylphenyl)-N,N-dimethyl~inoph~phine (7). An oven-dried, 250 mL, threenecked,round-bottomedflask wasfitted with a pressureequalizingaddition funnel, 2 glassstoppersand a magneticstirring bar. The vesselwaspurgedwith argon, chargedwith dichloro-N,N-dimethylaminophosphine2’ (1.83 g, 12.5 mmol, 1 equiv) in diethyl ether(50 mL) and cooledto -78 “C. A solutionof 4-lithio-3-methylanisole(70.0 mL of a 0.357 M solutionin diethyl ether, 25.0 mmol, 2 equiv) wasadded slowly via additionfunnel. Upon completionof the addition, the mixture waswarmedslowly to 25 “C over a periodof 1 h. After dilution with anhydrousdiethyl ether (20 mL), the mixture wasfiltered through activity II neutralaluminaundera constantflow of argonandconcentratedin vacua. The resultingresidue waspurified by distillation (160-165“C, 5 ~Torr) to afford 3.33 g (84%) of 7 asa highly viscouscolorless oil: ‘H NMR (300 MHz, CDCl,) 6 6.99 (dd, J = 3.9, 8.4 Hz, 2H, Ar-H), 6.70 (m, 4H, Ar-H), 3.78 (s, 6H, OCH,), 2.65 (d, J = 8.2 Hz, 6H, N(CH,)J, 2.27 (s, 6H, CH,); 3’PNMR (202 MHz, CDCl,) 6 49.7 (9. ~is(4-metboxy-2-metbylphenyl)phosphine]tribydroboron (6c). An oven-dried, 250 mL, threenecked,round-bottomedflask wasfitted with a glassstopper,a gas-inletadapteranda magneticstirringbar. The vesselwaspurgedwith argon, chargedwith 7 (0.850 g, 2.68 mmol, 1 equiv) in diethyl ether (107 mL) andcooledto 0 “C. Anhydroushydrogenchloride (0.219 g, 6.00 mmol, 2.2 equiv) wasslowly bubbledinto the solutionwhereupona white precipitateformed. The reactionmixture waswarmedto 25 “C and stirred
7662
L.
MCKINSTRY
and T. LIVINGHOUSE
for 5 h. The precipitateddimethylaminehydrochloridewasfiltered undera streamof argonand the filtrate wasconcentratedin vacua. The resultingbis(4-methoxy-2-methylphenyl)chlorophosphine wasredissolvedin tetrahydrofuran(1.5 mL) andaddedslowly, via additionfunnel, to an oven-dried,round-bottomedflask containinglithium aluminumhydride (0.122g, 3.20 mmol, 1.19 e&v), boranemethyl sulfide (0.320 mL of a 10.2 M solution,3.25 mmol, 1.25 equiv) and tetrahydrofuran(2.0 mL), at 0 “C. Upon completionof the addition, the mixture waswarmedto 25 “C and stirredfor an additional2 h. Excesslithium aluminum hydride wasquenchedwith aqueoushydrochloric acid (5 N, 1.5 mL) and ice (3.0 g), andthe biphasic mixture wasdiluted with diethyl ether (4.0 mL). The organicphasewasseparated and the aqueousphase wasextractedfurther with two 2-mL portionsof diethyl ether. The organiclayerswere combined,washed with brine (5.0 mL), dried (MgSO,) and concentratedunderreducedpressure.The resultingviscousbeige residuewaspurified by flashchromatographyon silicagel (20% ethyl acetate-hexane for elution) to give 317 mg (42%) of 6e asa white crystallinesolid: mp 97.3-99.9 “C; ‘H NMR (300 MHz, CDCl,) 6 7.50 (dd, J = 8.9, 13.6Hz, 2H, Ar-H), 6.76 (br s, 4H, Ar-H), 6.39 (dq, J = 6.5 Hz, JHep= 376 Hz, IH, P-H), 3.79 (s, 6H, OCH,), 2.28 (s, 6H, CH,), 1.54-0.38(br envelope,3H, BH,); “C NMR (75 MHz, CDCl,, ‘H decoupled)6 162.3(C), 143.9 (c), 143.7(c), 135.8(CH), 135.6(clf), 117.1(CH), 117.0 (m, 111.8 (Cl-I), 111.6 (CH), 75.2 (C), 70.3 (Q, 55.2 (CH,), 21.1 ((X-I,); ,]I’ NMR (202 MHz, CDCI,) 6 -17.0 (d, JP-H= 415 Hz); IR (film) 2358, 1599, 1564, 1489, 1455, 1303, 1242, 1079cm-‘; high resolutionmass spectrumc&d. for C&,,O,P (I&-BH,) 274.1124,found 274.1122. (2S,SS)-2,SHexanediol(8). The title compoundwaspreparedfrom acetonylacetone(5.71 g, 50.0 mmol, 1 e@iv) accordingto the methodof Lieser.“’ The mixture wasfiltered throughc&e andthe solidswererinsedwith four 50-mL portionsof ethyl acetate. The organicportion of the filtrate was separated and the aqueouslayer wassubjectedto continuousextraction with ethyl acetatefor 3 days. The combinedorganicextractswere dried (MgSO,) andconcentratedunderreducedpressureto yield a viscous beigeoil. Purification of this materialwasaccomplished by columnchromatographyon silicagel (ethyl acetatefor elution) to yield 4.49 g (75%) of 8 asa white solid. Recrystallizationfrom r-butyl-methyl ether afforded3.96 g (67%) of 8 as a white crystallinesolid: mp 50.4-53.2 “C; [a];’ + 35.2” (~~14.7, CHCl,), lit 21b[a]? + 34.9” (c=9.48, CHC13);‘H NMR (300 MHz, CDCl,) 8 3.78 (m, 2H, CH), 3.15 (br s, 2H, Oh), 1.53 (m, 4H, CHJ, 1.17 (d, J = 6.2 HZ, 6H, CH,); “C NMR (75 MHZ, CDCI,, ‘H decoupled) 6 68.1 (CH), 35.9 (CHJ, 23.6 (CH,). (2S,SS)-2,SHexanedioldi-p-toluenesulfonate(la). An oven-dried,round-bottomedflaskequipped with a rubberseptumanda magneticstirring bar waschargedwith (2S,SS)-2,5-hexanediol (1.18 g, 10.0mmol, 1 equiv), dichloromethane (30 mL) andpyridine (1.58 g, 20.0 mmol, 2 equiv). The solution wascooledto 0 “C andthenp-toluenesulfonylchloride (3.80 g, 20.0 mmol, 2 equiv) wasaddedin several smallportionsover a periodof 1 h. The mixture wasstirredat 0 “C for an additional19 h. The resulting white suspension wasdilutedwith dichloromethane (15 mL) andpartitionedbetween 10%aqueous hydrochloricacid solution(10 mL) anddichloromethane (5 mL). The organiclayer wasseparatedand the aqueouslayer wasextractedfurther with two lo-mL portionsof dichloromethane.The combinedorganic layerswerewashedwith another lo-mL portion of 10%aqueoushydrochloric acid solution,two 10-mL portionsof saturatedaqueoussodiumbicarbonatesolutionand dried ma,SO,). The solventswereevaporated underreducedpressureandthe resultingwhite solidwaspurified by recrystallizationfrom 10%heptanein methylcyclohexaneto yield 3.54 g (83%) of la asa white crystallinesolid: mp 94.5-97.0 “C; ‘H NMR (300MHz, CDCI,) 8 7.75 (d, J = 8.2 Hz, 4H, Ar-H), 7.32 (d, J = 8.2 Hz, 4H, Ar-H), 4.50 (m, 2H, CH), 2.43 (s, 6H, Ar-CH,), 1.54(m, 4H, CHJ, 1.11 (d, J = 6.3 Hz, 6H, CH,); “C NMR (75 MHz, CDCl,, ‘H decoupled)6 144.6(CJ, 134.8(CJ, 129.8(CI-I), 127.7(CH), 79.0 (c’H), 31.7 (CH,), 21.6 (GI,), 20.8 (CE,); XR(KBr) 3004,2980,2954,2930, 1598, 1450, 1438, 1378, 1323, 1308, 1294, 1189, 1171, 1096, 892, 852, 820, 758, 688, 578, 544, 522cm-‘. (lS,2S)-1,2-Bis[(diphenylphosphino)metbyl]cyclohexan~~P’-hexahydrodiboron (2a). An oven-driedroundbottomedflask equippedwith a magneticstirring bar waschargedwith (diphenylphosphine)trihydroboron (6b) (0.928 g, 4.64 mmol,2.1 equiv) andpurgedwith argon. The
C-Chiral bisphosphines
7663
reactionmixture wascooledto -78 “C and n-butyllithium (1.07 mL of a 4.50 M solutionin heptane,4.68 mmol,2.12 equiv) wasaddeddropwisevia syringeover a periodof 10 minutes. The reactiOnmixture waJ stirredat -78 “C for an additional10 minutesandthenwarmedto 25 “C for 10 min. The reaction mixture wasthencooledIO-40 “C and a solutionof (lS,2s)-1,2-di@-tosyloxymethyl)cyclohexaneD (1.00 g, 2.21 mmol, 1 equiv) in N,N-dimethylformamide(9.2 n&) wasaddedslowly via syringe. Uponcompletionof the addition, the mixture waswarmedslowly to 25 “C andstirredfor an additional9 h. The mixture was partitionedbetweendiethyl ether (20 mL) and 10%aqueoushydrochloric acid solution(25 mL). The organic layer wasseparated and the aqueouslayer wasextractedfurther with two 20 mL portionsof diethyl ether. The organiclayerswere combined,washedwith two 20 mL portionsof water andone20 mL portion of brine, dried (@SO,) andconcentratedin vacua. The resultingcolorlessresiduewaspurified by flash chromatographyon silica gel (40% ethyl acetate-hexanes for eiution) to yield 1.02 g (93%) of 2a a~a colorlesssolid. mp 184-189“C [CL]: + 15.6 “(C 0.027, CHCl,) ‘H NMR (75 MHz, CDCI,) 6 0.5-1.6 (br envelope,16H, Cy-H, CH, and BH,); 1.85 (ddd, 2H, J=14.2, 7.1, 6.7, P-CHEI); 2.19 (appt, 2H, P-Cl-W'); 7.26-7.47 (m, 12H, ArH); 7.54-7.60 (m, 4H, ArEI); 7.65-7.71 (m, 4H, ArH); “C m (300 MHz, CDCl,, ‘Hdecaupled)6 25.4, 29.5,29.9, 34.7, 38.3,38.4, 128.7, 128.8, 130.2, 130.3, 130.9, 131.0, 131.2, 132.1, 132.2, 132.4, 132.5; “P NMR (202, CDCl,) 6 13.96(S); IR (Ccl,) 3080, 3061, 3026, 3010,2932,2856.2384,2344,2254, 1958,1895,1814,1736, 1485, 1437, 1408, 1261, 1186, 1131, 1108, 1060,1028, 1000,958, 909, 866; high resolutionmassspectrumcalcd for &H,,PB, (I@-BHJ 493.4293, found493.4290. (1S,2S)-1,2-Bis[(dicyclohexylphosphino)methylleye~ (2b). The reactionof the lithium derivative of (dicyclohexylphosphine)trihydrobvron (6a) (56.1 mg, 0.263 mmd, 2.1 equiv) with ( l&25’)-1,2-di(p-tosyloxymethyl)cyclohexaneZ (56.5 mg, 0.125 mmol, 1 e@v) in tetrahydrofuran(2.0 mL) wascarriedout asdescribedfor 2e. After the describedworkup, evaporationof the solventsunderreducedpressureyielded 59.2 mg (89%) of 2h asa white residue. Purification by recrystallizationfrom heptaneaffordeda white crystallinesolid: mp 93.6-96.2 ‘C; [a]:: +10.7” (C = 0.06, CHCl,); ‘H Nh4R (300MHz, CDCL,)6 2.00-1.46 (br envelope,34H, Cy-H andCHJ, 1.45-1.00 @r envelope,28H, Cy-H andCH& 0.90-0.40 @r envelope,6H, BH,); “C NvfR (75 MHz, CD% ‘H decoupled)6 38.7, 38.6, 33.9, 33.2, 33.1, 32.7, 32.6, 27.8, 27.1, 27.0, 26.9, 26.6, 26.1, 25.8,24.9, 23.8, 23.4; 3’PNh4R(202 MHz, CDCl,) 1525.8 (s); IR (film) 2927, 2853, 2372, 1447, 1063cm-‘; high resolution massspectrumcalcd. for C,,H&P,(M+-BH,) 517.4293,found 517.4248. (2R,4R)-2,~Bis(dicyclohexylphosphino)pentane-P:P’-hexahydrodihoron(2~). An oven-dried, round-bottomedflask equippedwith a magnetic&ring bar anda rubber septumwaschargedwith (dicyclohexylphosphine)trihydroboron (6a) (54.7 mg, 0.263 mmol, 2.1 equiv), tetiydrofulan (0.5 mL) and purgedwith argon. Upon coolingto -78 ‘C, n-butyllithium (40.3 pL of a 7.17 M solutionin heptane, 0.289 mmol, 2.3 equiv) wasaddeddropwisevia syringeover a periodof 10 min, followedby the additionof hexamethyiphosphorictriamide(0.5 mL) to the reactionflask. The mixture wasstirredat -78 “C for 30 min then warmedto 0 “C for 20 min. After coolingto -40 “C, a solutionof (2S,4J3-2,4-pentanediol dip-toluenesulfonate p (51.5 mg, 0.125 mmol, 1 equiv) in NJ-dimethylformamide (0.5 mL) wasadded drapwisevia syringe. Upon completionof the addition, the mixture waswarmedslowly lo 25 “C and shxd for an additional3 h. The mixture waspartitionedbetweendiethyl ether (1.0 mL) and 10%aqueoushydrochloric acid solution(1.5 mL). The organiclayer wasseparated and the aqueouslayer wasextractedfurther with four I-mL portionsof diethyl ether. The organiclayerswere combined,washedwith tW02-n’& portionsof water andone 2-mL portion of brine, dried (MgSO,) andconcentratedin vacua. The resulting beigeresiduewaspurified by flashcolumnchromatographyon silica gel (10% ethyl acetate-hexane for elution)andthe materialthat wasobtined in this way wasrecryt&iz& from hexaneat 0 “C to yield 58 mg (91%) of 2c asa white solid: mp 92.1-94.6 “C; [a]; - 11.4” (c = 0.06, CHCI,); ‘H NMR (300 MHz, CDCl,) 6 2.04-1.57 @renvelope,24H, CH and Cy-H), 1.50-1.12 (br envelope,24H, CH, ad Cy-Hh 1.14 (dd, J = 7.1, 13.4 HZ, 6H, CH,), 1.01--0.20 (br envelope,6H, BH,); ‘T NMR (75 MHZ, CDCl,, ‘H decoupled)8 34.9, 34.5, 26.5, 26.4, 25.9, 25.7, 24.8, 22.3, 13.9; 3’p N&~R(202MHz, CDCI,) 8 24.1 (s);
7664
L. MCKINSTRYandT. LIVINGHOUSE
IR (film) 2929, 2852, 2365, 1449,889 cm-‘; high resolutionmassspectrumcalcd. for CJ-I,,BP,(M+-BH,) 477.3950,found477.3949. (2R,5R)-2,5-Bis(dicyclohexylphosphino)hexaoe-P:P1-hexahydrodiboron (2d). The reactionof the lithium derivative of (dicyclohexylphosphine)trihydroboron (6a) (112 mg, 0.525 mmol, 2.1 equiv) with la (107 mg, 0.250 mmol, 1 equiv) wascarriedout asdescribedfor 2e. After the describedworkup, evaporationof the solventsunderreducedpressureyielded a white solid. This materialwaspurified by crystallizationfrom 10%ethyl acetatein hexanesto yield 107mg (86%) of 2d asa white crystallinesolid: mp 203.2-205.4“C; [a]: - 19.5” (c = 0.01, CHClJ; ‘H NMR (300 MHz, CDCI,) 6 1.95-1.60(m, 35H, Cy-H envelope),1.55-1.20(m, 15H, CH, CH, andCy-H envelope), 1.17 (dd, J = 7.0, 13.3 Hz, 6H, CHJ, 0.77--2.30 (br envelope,6H, BH,); 13CNMR (75 MHz, CDCI,, ‘H decoupled)6 31.6, 31.5, 31.2, 31.1, 30.5, 30.4, 28.2, 27.9, 27.8, 27.7, 27.3, 27.2, 26.1, 25.4, 25.0, 14.6; ‘iP NMR (202 MHz, CDC13)8 31.1 (br s); IR (film) 2927, 2853, 2362, 2342, 1067cm-i; high resolutionmassspectrumcalcd. for C,JIJ3P,(M+-BH,) 492.4185,found 492.4210. (2R,SR)-2,5-Bis(diphenylph~p~o)hexan~~P’-hex~y~o~bo~n (2e). An oven-dried,roundbottomedflaskequippedwith a magneticstirring bar anda rubberseptumwaschargedwith (diphenylphosphine)trihydroboron (6b) (100 mg, 0.50 mmol, 2.1 equiv), tetrahydrofuran(1.5 mL) and purgedwith argon. Uponcooling to -78 “C, n-butyllithium (88.0 PL of a 5.80 M solutionin heptane, 0.5 1 mmol, 2.12 equiv) wasaddeddropwisevia syringeover a period of 10 min. The reactionmixture was stirredat -78 “C for an additional10 min andthenwarmedto 25 “C for 10 min. Upon coolingto -40 “C, a solutionof la (102 mg, 0.24 mmol, 1 equiv) in N,N-dimethylformamide(1.O mL) wasaddedslowly via syringe. Upon completionof the addition,the mixture waswarmedslowly to 25 “C andstirredfor an additional9 h. The mixture waspartitionedbetweendiethyl ether (2.0 mL) and 10%aqueoushydrochloric acid solution(3.0 mL). The organiclayer wasseparated andthe aqueouslayer wasextractedfurther with four 2-mL portionsof diethyl ether. The organiclayerswerecombined,washedwith two 2-mL portionsof waterandone2-mL portion of brine, dried (MgSO,) andconcentratedin vacua. T’heresultingbeigeresidue waspurified by flashcolumnchromatographyon silicagel (20% ethyl acetate-hexane for elution) to yield 102mg (88%) of 2e asa white solid: mp 153.4-154.8“C; [a]; + 35.2” (c= 14.7, CHCI,), lit.2lb [a]3 -9.5“ (c = 0.01, CHCl,); ‘H NMR (300 MHz, CDCI,) 6 7.68-7.62 (m, 8H, Ph-H), 7.47-7.36 (m, 12H, Ph-H), 2.37 (appSept.,J = 7.4 Hz, 2H, CH), 1.52 (m, 4H, CHJ, 1.01 (dd, J = 6.9, 16.5 Hz, 6H, CH,), 1.45-0.20(br envelope,6H, BH,); “C NMR (75 MHZ, CDCI,, ‘H decoupled)6 132.7(CH), 132.6(CH), 132.5(C’H), 132.4(CID, 131.1 (CH), 128.9(c), 128.8(C’H), 128.7 (CH), 128.6(CH), 128.3(c), 29.5 (CH), 29.4 (CH), 28.7 (CH2), 28.2 (CHJ, 13.7 (CH,); 31PNMR (202 MHZ, CDCI,) 6 23.9 (s); IR (film) 2928, 2385, 1436, 1107, 1064cm-‘; high resolutionmassspectrumcalcd. for C3&13,P,(M+-B&) 454.1982, found 454.1980. (2R,2R)-2,5-Bis[bis(4-methoxy-2-methylphenyI)phosphino]hexane-P:P’-hexahydrodiboron (2f). The reactionof the lithium derivative of [bis(4-methoxy-2-methylphenyl)phosphine]trihydroboron (SC) (154 mg, 0.525 mmol, 2.1 equiv) with la (107 mg, 0.250 mmol, 1 equiv) wascarriedout asdescribedfor 2e. After the describedworkup, evaporationof the solventsunderreducedpressureyielded a white solid. This materialwaspurified by crystallizationfrom methylcyclohexaneto yield 135mg (82%) of 2f asa white crystallinesolid: mp 149.3-153.1“C; [a]P -20.4“ (c = 0.02, CHCl,); ‘H NMR (300 MHz, CDCl,) 6 7.77 (dd, J = 11.5, 10.5Hz, 2H, Ar?H), 7.49 (appt, J = 10.5Hz, 2H, Ar-H), 6.77 (appd, J = 8.5 Hz, 4H, Ar-H), 6.66 (appd, J = 17.2 Hz, 4H, Ar-H), 3.81 (s, 6H, OCH,), 3.79 (s, 6H, OCH,), 2.54 (m, 2H, CH), 2.08 (s, 6H, CH,), 1.99 (s, 6H, CH,), 1.76 (m, 4H, CHJ, 1.07 (dd, J = 6.8, 16.5 Hz, 6H, CH,), 1.902 (br envelope,6H, BH,); 13CNMR (75 MHz, CDCl,, ‘H decoupled)6 161.7, 161.0, 144.7, 144.2, 135.8, 135.3, 134.1, 133.6, 129.7, 127.6, 117.6, 111.1,79.5, 55.0, 28.1, 27.7, 21.7, 20.3, 14.4; “PNMR (202 MHz, CDCI,) 6 21.4 (s); IR (film) 2933, 2383, 1598, 1565, 1489, 1464, 1302, 1237, 1075 cm-‘; high resolutionmassspectrumcalcd. for C,,H.,,O,P,(M+-%Hd 630.3030,found 630.3028.
C-Chiral bisphosphines
7665
Preparation of Biiphosphine Ligands 3d-f. Representative Procedure for PhosphineBomne Decomplexation with HBF,*OMep: (ZR,!X)-2,5-Bi(diphenylphosphino)hexane (3e). A flame-dried test tube (16 mm x 100 mm) equipped with a stirring bar and a rubber septum was charged with 2e (48.2 mg, 0.10 mmol, 1 equiv), dichloromethane (1.0 mL) and purged with argon. Upon cooling to -5 “C, tetrafluoroboric acid dimethyl ether complex (134 mg, 1.00 mmol, 10.0 equiv) was added dropwise by syringe. An exothermic reaction ensued and gas evolved. The reaction mixture was then’warmed to 25 “C and stirred for an additional 12 h. Subsequently, the mixture was diluted with degassed, anhydrous diethyl ether (2.0 mL) and added to degas&, saturated aqueous sodium bicarbonate solution (5.0 mL) contained in a small Erlenmeyer flask. The resulting biphasic mixture was stirred vigorously under argon for 10 min and thenpouredinto a separatoryfunnel. The organiclayer wasseparated andthe aqueouslayer wasexbacti (WI&Y argon) with two 2-mL portionsof degassed, anhydrousdiethyl ether. The organiclayerswere combined,washedwith two 3-mL portionsof degassed water andone3-mL portion of brine, dried (MgSO,) (all un&r argon) andconcentratedin vacua. The resultingwhite solidwasrecrystallizedfrom degassed methylcyclohexaneat 0 “C to give 45.3 mg (99%) of 3e asa white crystallinesolid: mp 179.3-183.6“C; [[I]~~ f7.0” (c = 1.0, CHCl,); ‘H NMR (300 MHz, CDC&) 6 7.67 (m, 8H, Ar-H), 7.55-7.38 (m, 12H, k-H), 2.25 (m, ZH, CH), 1.61 (m, 4H, CH3, 1.03 (dd, J = 7.1, 17.0 Hz, 6H, CH,); 13CNMR (75 MHZ, CDCl,, ‘H decoupled)131.4, 130.9, 128.4, 32.8, 32.1, 27.6, 11.9; 3’P NMR (202 MHz, CDCI,) 6 -1.8 (s); IR (KBr) 3068, 3052, 2956, 2930,2880, 2852, 1480, 1458, 1432, 1376, 1196, 1092, 1068, 1026,738, 696, 658, 510 cm-‘; high resolutionmassspectrumc&d. for C&32P,(M+) 454.1982,found 454.1979. (2R,4%2,4-Bii(dicyclohexylphosphino)peutane (3~): white solid; yield (91%); mp 182.3-184.9“C; ‘H NMR (300MHz, CDCl,) 6 2.03 (m, 2H, CH), 1.95-l .64 (m, 22H, Cy-H envelope),1.53 (s, 2H, CH& l-47-1.15 (m, 22H, Cy-H envelope),1.15 (dd, J = 7.1, 13.3 Hz, 6H, CH,); ‘%I NMR (75 MHz, CDCI,, ‘Hdecoupled)6 31.8, 31.1, 30.0, 28.1, 27.8, 27.5, 27.3, 27.2, 26.0, 25.4, 25.0, 15.8; “PNMR (202 MHz, C$J 6 6.5 (s); high resolutionmassspectrumcalcd. for C&,P,(M+) 464.3704,found 464.3700. (2R,SR)-2,5-Rk(dicyclohexyIphosphino)hexane(3d): white solid; yield (91%); mp 184.6-187.3“C; ‘H NMR (300 MHz, CDCI,) 6 1.96-1.60(m, 35H, Cy-H envelope), 1.60-1.05(m, 15H, CH, CH, andCyH envelope),1.16 (dd, I = 7.2, 16.1 Hz, 6H, CH,); “C Nh4R (75 MHz, CDCI,, ‘H decoupled)6 35.9, 35.1, 30.2, 29.4, 28.7, 28.5, 27.0, 26.9, 26.8, 26.6, 26.5, 26.3, 26.1, 13.3; “P NMR (202 MHz, CDCl,) 8 11.1 (s); IR (film) 2929, 2852, 1449, 1157cm-‘; high resolutionmassspectrumcalcd. for C,&,P,(M+-H) 477.3783, found477.3780. (2R,SR)-2,5-Bis[bis(emethoxy-2-methylphenyl)phosphino]hexane (32): white solid; yield (96%); mp 178.4-181.9“C; ‘H NMR (300 MHz, CDC13)6 7.17-7.08 (m, 4H, Ar-H), 6.71-6.63 (m, 8H, Ar-H), 3.78 6, 6H, OCH,), 3.74 (s, 6H, OCH,), 2.44 (s, 6H, CH,), 2.37 (s, 6H, CH,), 2.10 (m, 2H, CH), 1.47 (m, 4H, CHJ, 0.89 (dd, J = 6.8, 16.0 HZ, 6H, CH,); 13CNMR (75 MHZ, c~cl,, ‘H decoupled)6 159.7, 144.8, 144.6, 133.2, 132.5, 115.7, 115.6, 111.7, 54.9, 52.0, 31.5, 30.5, 29.6, 21.4, 16.1, 15.8; 3’PNMR (202 MHz, CDC13)6 -32.4 (s); IR (film) 2925, 2852, 1595, 1564, 1483, 1464, 1296, 1238, 1071cm-‘; high resolutionmassspectrumc&d. for C,,H,,O,P,(M+) 630.3030,found 630.3028.
LITERATURE CITED AND FOOTNOTES 1. 2. 3. 4.
Fellow of the Alexander von HumboldtFoundation1993-1995. Noyori, R. AsymmetricCatalysisin OrganicSymhesis.JohnWiley andSons: New York, 1994. Pietrusiewicz,K. M.; Zablocka,M. them. Rev. 1994,94, 1375. For a review see: Kagan, H. B.; Sas&i, M. In TheChemistryof Organophosphorus COmpOUndr; Hartley, F. R., Ed.; Wiley: New York, 1990;vol. 1, p. 51.
7666
5.
6. 7. 8. 9. 10. 11. 12. 13. 14.
15.
16. 17. 18. 19. 20. 21. 22. 23. 24. 25.
L.
MCKINSTRY
and T. LIVINGHOUSE
a) Kagan, H. B.; Dang, T. -P. J. Am, Chem.Sot. 1972,94, 6429. b) Dang, T. -P.; Poulin, J. C.; Kagan, H. B. J. Organomet. Chem. 1975, 91, 105. c) Morimoto, T.; Chiba, M.; Achiwa, K. Chem.Ph. Bull. 1992,40, 2894and referencescited therein. d) Inoguchi, K.; Fujie, N.; Yoshikawa,K.; Achiwa, K. Chem.Pharm. Bull. 1992, 40, 2921and referencescited therein. e) McNeil, P. A.; Roberts,N. K.; Bosnich,B. J. Am. Chem.Sot. 1981, 103, 2273. f) Fryzuk, M. D.; Bosnich,B. J. Am. Chem.Sot. 1977, 99, 6262. g) Hobbs,C. F.; Knowles, W. S. J. Org. Chem. 1981, 46, 4422 and referencescited therein. h) Hayashi,T.; Tanaka, M.; Ogata, I. J. Mol. Cuful. 1984,26, 17. i) Ojima, I.; Kogure, T. C&m. Lett. 1979, 641. j) Nagel, U. Angew. Chem.ht. Ed. Engl. 1984, 23, 435. k) Bakos,J. ; Toth, I.; Heil, B.; Marko, L. J. Organomet.Chem. 1985,279, 23. 1) Kagan,H. B.; Fiaud, J. C.; Hoomaert, F. C.; Meyer, D.; Poulin, J. C. Bull. Sot. Chim.Belg. 1979, 88, 923. In selectedinstances,eliminationhasbeenminimizedby the useof cyclic sulfatesassubstrates in displacementreactionswhich employan unhinderedlithium phosphideasa nuclephile: Burk, M. J. J. Am. Chem.Sot. 1991,113, 8518. Tani, K.; Suwa, K.; Yamagata,T.; Otsuka,S. Gem. Len. 1982,265. a) Imamoto, T. PureAppl. Ckm. 1993, 65, 655 andreferencestherein. b) Imamoto,T.; Oshiki, T.; Onozawa,T.; Kusumoto,T.; Sato, K. J. Am. Chem. Sot. 1990,112, 5244. a) During the courseof this work a singleexamplewasreportedin which the lithium derivative of diphenylphosphine-borane wasusedto synthesize. DIOP.9b b) B&et, H.; Gourdel, Y.; Pellon, P.; Le Corre, M. TetrahedronLen. 1993,34, 4523. McKinstry, L.; Livinghouse,T. TetrahedronL&t. 1994, 35, 9319. The useof old, alkoxidecontaminatedsamples of n-BuLi for this purposeresultsin greatly diminishedyieldsof the desiredsubstitutionproducts2a-f. Diastereomericpurity for 2a-f wasinferred by high field ‘H and “C NMR analysiswhich indicated the absenceof mesoisomers.In addition, 2a-f were homogeneous by HPLC and GLC. All new phosphine-borane complexeswerefully characterizedby ‘H, 13Cand “P NMR, IR and possessed satisfactorycombustionanalysesor exactmass. Severalalternative setsof conditionsintendedfor boranedecomplexationwere examinedandfound to be ineffective. Theseincluded: exposureof 2i to EtO-K+ in PhMe or THF; treatmentwith 18crown-6*K+CN- in Et$IH; andwarmingin the presenceof “catalytic” (10 mol %) (n-B&P in morpholine. A transientcompound[presumablythe monoboranecomplexDPPE*(BH,) (lo)] was observedat intermediatestagesof the reaction. An authenticsampleof 10 wasprepared(albeitwith poor selectivity) by the exposureof 3i (1.2 equiv) to BH,*SMe, (1.Oequiv) followed by chromatographic purification. As a moreeconomicalalternative,boranedecomplexationcould be readily effected (e.g., 25 “C, 4 h) by treatmentwith preformedHBF,vOEt, [BF,*OEtr (1 equiv) + I-IF& (1 equiv)]. Ether complexesof BF, and HBF, wereobtainedfrom Aldrich ChemicalCo. In contrast, the 1,3dioxolanelinkagepresentwithin the bisboranederivative of DIOP wasdegraded underthe prescribedsetof reactionconditions. Still, W. C.; Kahn, M.; Mitra, A. J. Org. C&m. 1978, 43, 2933. 4-Bromo-3-methylanisole waspreparedaccordingto a literatureprocedure: Oshiki, T.; Imamoto,T. Bull. Chem.Sot. Jpn. 1990, 63, 3719. Noth, H.; Vetter, H. -J. ~Chem.Ber. 1963, 96, 1109. a) Lieser, J. K. Synfh. Commun.1983, 13a, 765. b) Short, R. P.; Kennedy, R. M.; Masamune,S. J. Org. #em. 1989,54, 1755. The requisiteditosylate9 waspreparedfrom (2S,4S)-2,4-dihydroxypentane by treatmentwith p-toluenesulfonylchloridein the presenceof pyridine (vi& supra). Preparedand characterizedby Mr. D. J. Sheehanof theselaboratories. Analogousdecomplexationof 2a2’ on a 1 mmolscaleprovided3a in 97% isolatedyield. Preparedon a 2.21 mm01scalein 93%yield by Mr. D. Belangerof theselaboratories.
(Received in USA 22 December 1994; accepted 9 May 1995)