Arthur Cammaratal Bryn Mawr College Bryn Mowr, Pennsylvania
I
I
Optical Studies in Organophosphorus Chemistry
Utilization of the optical rotatory properties of asymmetric carbon compounds has provided a reasonably clear picture of the stereochemical changes accompanying reaction of these materials (1 ). Only recently, however, have optical studies been applied to the reactions of organophosphoms compounds (2). Although it is still too early to discuss the stereochemistry of reactions on phosphorus with the same degree of sophistication that can be applied to reactions on carbon, it is both interesting and instructive to trace the development of this relatively new field. Since nucleophilic displacements on optically active phosphates, thiophosphates, and chloridates have been discussed adequately elsewhere ( d ) , this paper will present those reactions which have been studied using optically active phosphines and phosphonium salts. The present revival of interest in phosphorus stereochemistry perhaps began with the resolution of phosphonium salts I and I1 (3, 4). A number of earlier workers had attempted the resolution of phosphonium
salts but all met with failure (5-13), apparently as a result of the inherent difficulties in crystallizing these compounds (4). The first optically active quaternary phosphorus compound obtained, in which the phosphorus atom was not incorporated in a heterocyclic ring, was resolved v i a its dibenzoylhydrogen-tartarate salt (14). A number of phosphonium salts have been resolved since then by the same method (15-17). The absolute configuration of one of these salts, (+)-benzylmethylpheuyl-n-propylphosphonium bromide, 111, has recently been determined (18).
III Optically active phosphonium salts are reduced by lithium aluminum hydride to give racemic phosphines (16); electrochemical reduction, using a mercury
cathode, forms optically active phosphmes (15). Optically active phosphines retain their configuration on alkylation and sulfuration (16); oxidation with hydroperoxides results in retention of configuration (15, l o ) , but with t-butylhypochlorite in methanolic-methylene chloride, inversion of configuration is noted (19). I n the absence of methanol, the latter leads to almost complete racemizat,ion; this was construed as supporting the following mechanism (19): RSP
+ CI-OCRS
64
/ Journal o f Chemicol Edumfion
retention
HOCHs O=PRI
-
+ CHE~
+
R ~ ~ ~ - C I CH~OH. . . O C R ~
+1
inversion
CH~O-~~R~ ci-
(1)
+ RCOH
Heating optically active phosphines a t atmospheric pressure results in their racemization (15). The kinetics of racemization of (+)-methylphenyl+propylphosphine have been measured and the energy of activation for the process determined as being about 30 kcal/mole (20). Reaction of optically active phosphine with halogens, followed by hydrolysis, leads to racemic phosphine oxide ($1). In aqueous acetonitrile, reaction with halogens leads to phosphine oxide of inverted configuration (21). These results are consistent with a mechanism in which an optically active phosphonium salt, formed initially, is in equilibrium with a pentacovalent phosphorus compound, which itself is initially, a t least, in the form of a symmetric trigonal-bipyramid. Subsequent to the formation of this initial trigonal-bipyramidal structure, internal motion-i.e., flipping of the
(2)
groups' posit,ions-could
occur (22). This conclusion
appears to be strengthened by the observations that: (a) optically active phosphoniurn salts react with sodium hydroxide to form phosphine oxides of inverted configuration (28, 24); and, (b) optically active Rl..,+
HO-
'Postdoctmd fellow at Bryn Maw, 1964-65. Current address, Dept. of Pharmaceutical Chemistry, Medical College of Virginia, Richmond 19, Virginia.
-
+ RI-P-X
-
phosphine oxides racemize in the presence of anhydrous
hydrochloric acid (35). I t should be noted that nucleophilic displacements on phosphorus do not necessitate the nucleophile, phosphorus atom, and leaving group to be collinear, for, as has been pointed out (%),a transition state in which these groups are part of the basal plane of a trigonal hipyramid would result in the same stereochemical change. Optically active phosphonium salts containing a 2-cyanoethyl group undergo reaction with sodium ethylate to give optically active phosphines and 3-ethoxypropionitrile (16).
In the presence of phenyl-lithium, optically active benzylethylmethylphenylphosphonium iodide affords the corresponding phosphorane with retention of configuration (36). Reaction of this phosphorane with benzaldehyde gives phosphine oxide with a high degree of retentionof configuration (36),thus confirminga cyclic transition state for t,he Wittig reaction. Similarly, reacPh
Ph CH
\A':
Ph
\
CH-CH
8
PhCHO
\A':
CIH* ~h CH,
/
h+ A-
0
+
P'I .','.,
(6)
C~H;~h CHI
C * H ~~h CHZ
tion with benzonitrile affords an intermediate, which upon treatment with alkali, yields phosphine oxide with 68% inversion of configuration @7), thus showing that two paths are involved, one proceeding with retention of configuration, the other with inversion of configuration. Ph
Ph
/
\
CH-C
I
/I
Ph &
N-
RsP+
HART,F. A., A N D MANN,F. G., J. Chem. Soc., 4107 (1955). MICHAELIS. A.. Ann..,~ 315. 19 11Qnl l --,-. ~ MICHAELIS; A.; Ann., 315, 43 (1901). WEDEKIND, E., Ber., 45, 2933 (1912). POPE, W. J., A N D GIBSON,C. S., J . Chem. Soc., 101, 735 11(111>
(10) MEISENHEIMER, J., ET AL.,Ann., 449, 213 (1926). G . , J . Gen. Chem. (U.S.S.R.), 2, 524(1932). (11) KAMAI, G., Doklady. Akad. A'aukS.S.S.R., 92, 69 (1953). (12) KAMAI, L. A,, J . Ga. Chem. (13) KAMAI,G., AND KHISMATULLINA, (C.S.S.R.) (English Translation), 26, 3815 (1956). W. E., AND VANDERWERF, C. A,, (14) KUMLI,K. F., MCEWEN, J . Am. Chem. Soc., 81, 248 (1959). L., ET AL., Tetrahed~mLette~s,No. 5, 161 (1961). (15) HORNER, , E., ET .AL.,Abstracts of Papem, 140th ACS (16) M c E w ~ n \V. Meet,ing, Chicago, September 1961, p. 96Q. L., SCHEDLBAUER, F., AND BECK,P., Tetrahedmn (17) HORNER, Letters, No. 22, 1421 (1964). A. F., ET AL.,Tetrahedron Letters. No. 13. 811 (18) PEERDEMAA, (1965). (19) DENNEY.D. B., A N D HANIFIN,J. W., JR., Tetmhedmn Letl?rs, NO.30, 2177 (1963). L., A N D WINKLER,H., Tetrahedra Letters, No. 9, (20) HORNER, 461 ...119641 ~
(21) HORNER, L., A N D WINKLER, H., Tetrahed~mLetters, No. 9, 455 (1964). E. L., MAHLER,W., AND SCHMUTZLER, R., (22) MOETTERTIES, Inorg. C h m . , 2,613 (1963). C. A,. AND MCEWEN.W. E.. (23) . . KUMLI.K. F.. ~'ANDERWERF. J . ~ k~ h. & .Soe., 81, 3805 (1959). I,., .AND WIKKLER, H., Tetmhedmn Lettem, No. 3. (24) HORNER, 17.5 (10641 ~
(25) DENNEI, I). B., TSOLIS,A. K., A N D MISLOW,K., J . Am. C k m . Soc., 86, 4486 (1964). .4, VANDERWERF, C. A,, A N D MCEWEN, (26) BL.&DE-FONT, M-.E., J. . 4 m Chem. Soc., 82, 2396 (1960). A . TIANDERWERF. C. A,. AND MCEWEN. (271 . . BLADE-FONT. W. E., J. k m . ~ h e r n Soc., . 82, 2646 (1960). A,, A N D VANDERWERF, (28) MCEWEK,\V. E., BLAD~-FoNT, C . A , , J . . 4 n ~Chem. Soe., 84,677 (1962).
Ph
C-
R,b+
retention
R P 4
'-'d
(41 (5! (6) (7) (8)
0
II
AH
I
OH-, inversion
t
+ PhCHsCPh + 0=PRa
The same phosphorane was shown to react with styrene oxide to form a betaine, which upon pyrolysis a t 190-200' yielded, among other products, racemic phosphine and phosphine oxide of 50% net inverted configuration (38). Racemic phosphine presumably arose as a consequence of the thermal racemization of optically active phosphine. A concerted, base assisted decomposition of a pentacovalent intermediate has been suggested to lead to inverted phosphine oxide by analogy with other nucleophilic displacements on phosphorus. Literature Cited (1) ELIEL, E. L., "Stereochemistry of Organic Compounds," McGraw-Hill Inc., New York, 1962. (2) HUDSON,R. F., AND GREEN. M., Angew. Chem. (International Edition in English), 2, 11 (1963). F. G., AND MANN,F . G., J. Chem. Soe., 1634 (31 HOLLIMAN, Volume 43, Number 2, Februory
1966
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