3869
The Stereochemical Course of Ester-Amide Interchange Leading to Optically Active Phosphinic and Sulfinic Amides'
Chart I
Sir : ( - )- (S)-I (R = cholesteryl) (-)-(S)-III In connection with our interest in the stereochemistry ( - ) - ( ~ ) - 1 1(R = menthyl) of substitution at sulfur2 and phosphorus, we have examined for the first time the stereochemical course of ester-amide interchange leading to optically active phosphinic and sulfinic amides. Two examples of optically active phosphinic amides have been previously prepared by other appro ache^,^ and one partially active sulfinic amide has been described. Chart I summarizes the reactions of substitution at asymmetric phosphorus that provide the conclusion that amide-ester interchange occurs with almost complete inkersion of configuration. One of the diastereomers of the cholesteryl phosphinate (-)-(S)-I,j mp 134-134.5, [ c r I 2 j ~-81.4" (c 4.53, chloroform), was obtained for the first time in 12% yield5 by chromatography (12 : 1 silica gel-ester mixture; 3 :2 ether-pentane eluent) of the mixture of diastereomeric esters produced by mixing equimolar amounts of methylphenylphosphinic chloride and cholesterol in pyridine at 25" for 10 hr. The menthyl ester was similarly prepared6 in 10% yield, m p 80", [crIz5~ -93.8' (c 1.45, chloroform). Ester (-)-(,!?)-I when treated in ether with benzylmagnesium chloride gave phosphine oxide (+)-(R)-IV in 84% yield, m p 148-148.2", [cr]*'~ $49.94" (c 1.64, methanol) (lit.6[ c Y ] ~+50.9"). ~D The correspondence of our and Korpium and Mislow's rotations coupled with these authors' establishment of the configuration of (+)-(R)-IV and the stereochemical course of the Grignard reaction (inversion) identifies the configuration at phosphorus of I and also demonstrates the diastereomeric purity of I. When either (-)-SI or (-)-(S)-I1 was treated with a 10 molar excess of lithium anilide in dry refluxing benzene for 12 hr, (-)-(S)-111 was produced : yield after chromatography and nonfractional crystallization from (-)-(S)-I, 35 %; mp 161-163 O ; ( + ) - ( S , S)-IX [ c Y ] ~-26.2' ~D (c 1.33, methanol) ( w b mp 164"; [cr]*j~ p-CHaCCH,SOCl (-)-(S)-V -25.8' (c 0.755, methanol)); yield from (-)-(9-11 (-)-CSWIX (+)-(S,S)-IX after fractional crystallization from acetone-pentane to remove the menthol, 38%; m p 161-163'; [a]25~ or (-)-(S)-I1 in dry refluxing benzene for -26.1 ' (c 0.83, methanol). Horner and W i ~ ~ k l e r (-)-(S)-I ~~ 12 hr. Chromatography of the product (silica gel, established the relative configuration of (+)-IV and acetone-ether) and nonfractional crystallization gave (-)-I11 and converted (+)-IV to (-)-I11 by a reaction only a single diastereomer (-)-(S)-VI, in 25% yield that involved substitution with retention of configurafrom (-)-(S)-I and 25% from (-)-(S)-11, mp 132tion (Chart I). Our conversion of (-)-I or (-)-I1 133.5, [ a I z 5 -63.0" ~ (c 1.55, chloroform (both preparato (-)-I11 and to (+)-IV completes a cycle of intertions)). Examination of the crude product by tlc conversions that indicates that the amide-ester interchromatography (silica gel plates, acetone-methanol change occurs with inversion at phosphorus. To de9 : 1) showed the absence of the other diastereomer in termine the generality of this conclusion, a 10 molar the mixture. Control experiments with diastereomers excess of the lithium salt (-)-(S)-V of cr-phenylethyl(see below) demonstrated that as little as 1-2% could amine ( [ c r I z 5 ~ -40.1", neat)' was mixed with either have been detected. These conversions demonstrate high stereospecificity in the substitution reaction at (1) This investigation was supported by U. S. Public Health Service phosphorus. Both optically pure diastereomers conResearch Grant KO.GM 12640-04 from the Department of Health, Education, and Welfare. figurationally identical at carbon were prepared by (2) J. Day and D. J. Cram, J . Am. Chem. Soc., 87, 4398 (1965). treating two parts of optically pure (-)-(S)-V7 with 1 (3) (a) I . G. M. Campbell and J. I
