(R)-(+)-3-(p-Tolylsulfinyl)propionic Acid

[90334-31-9]  · C10H12O3S  · (R)-(+)-3-(p-Tolylsulfinyl)propionic Acid  · (MW 212.29)

(asymmetric aldol-type condensation2)

Physical Data: [a]D = +180° (CHCl3, c = 0.7), [a]D = +188° (MeOH, c = 0.7).

Preparative Method: conveniently prepared in 76% yield by addition of a suspension of lithium bromoacetate to a solution of the anion of (R)-(+)-Methyl p-Tolyl Sulfoxide (eq 1).1,2

Aldol-Type Condensation.

Dimetalation of (R)-(+)-3-(p-tolylsulfinyl)propionic acid with Lithium Diisopropylamide produces a chiral homoenolate dianion equivalent which reacts with carbonyl compounds to afford b-sulfinyl-g-hydroxy acids; these spontaneously cyclize to give the corresponding b-sulfinyl g-lactones (eq 2).1,2

Two new chiral carbon atoms are formed in the condensation and four diastereoisomeric b-sulfinyl g-lactones can therefore in principle be obtained. However, only two diastereoisomers, (3S,4R,RS) and (3R,4S,RS), are isolated when the carbanion is condensed with pivalic aldehyde, benzaldehyde, or pinacolone (yield 65-70% for aldehydes, ratio 53:47; yield 47% for pinacolone, ratio 81:19). The diastereoselectivity decreases when the two substituents of the carbonyl group are sterically similar. However, single diastereoisomers can easily be separated through chromatography and transformed in high yield into both enantiomers of optically pure saturated (by desulfurization) and a,b-unsaturated g-lactones (by pyrolytic sulfoxide elimination) (eq 3). The relative and absolute stereochemistry of all the products have been determined by circular dichroism, nuclear Overhauser effects, and X-ray analyses.

The condensation of the dilithio derivative of (R)-(+)-3-(p-tolylsulfinyl)propionic acid with protected glycoaldehydes (O-t-butyl and O-benzyl) gives 5-alkoxy-4-hydroxy-3-(p-tolylsulfinyl)pentanoic acids, which spontaneously cyclize to the corresponding 3-sulfinyl-4-alkoxymethyl butanolides (eq 4).3 Pure diastereomers can be separated by flash chromatography and are obtained in comparable amounts. The corresponding optically pure butenolides are obtained by pyrolytic elimination of the sulfoxides and then transformed into natural (+)-(R)-umbelactone (eq 5).

1. Bravo, P.; Carrera, P.; Resnati, G.; Ticozzi, C. CC 1984, 19.
2. Albinati, A.; Bravo, P.; Ganazolli, F.; Resnati, G.; Viani, F. JCS(P1) 1986, 1405.
3. Bravo, P.; Resnati, G.; Viani, F. G 1987, 117, 747.

Guy Solladié & Françoise Colobert

University Louis Pasteur, Strasbourg, France

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