(R)-(+)-t-Butyl 2-(p-Tolylsulfinyl)acetate

[58059-08-8]  · C13H18O3S  · (R)-(+)-t-Butyl 2-(p-Tolylsulfinyl)acetate  · (MW 254.34)

(reagent for asymmetric aldol-type condensation;1 used for the synthesis of sulfinyl dienophiles13)

Physical Data: [a]D20 = +149° (EtOH, c = 2.25)

Preparative Methods: conveniently prepared2,3 by reaction of the magnesium enolate of t-butyl acetate (readily made with Bromomagnesium Diisopropylamide) with (-)-(1R,2S,5R)-Menthyl (S)-p-Toluenesulfinate (eq 1). It was also made in 91% yield by reacting a solution of Lithium Diisopropylamide with (R)-(+)-methyl p-tolyl sulfoxide and t-butyl carbonate (eq 2).4 It should be noted that asymmetric oxidation of t-butyl 2-(p-tolylsulfinyl)acetate with a modified Sharpless reagent gave a poor ee.5

Aldol-Type Condensation.

Aldol-type condensation of the magnesium enolate of (R)-(+)-t-butyl 2-(p-tolylsulfinyl)acetate, prepared with t-butylmagnesium bromide, with aldehydes and ketones afforded, after desulfurization with Aluminum Amalgam, b-hydroxy esters in very high diastereoselectivity (eq 3).3,6,7 Two chiral centers are created in the first step with very high diastereoselectivity (mainly one diastereomer is formed). A model M based on the structure of the sulfinyl ester enolate (determined by 13C NMR)8 and on electrophilic assistance of magnesium to the carbonyl approach, was proposed to explain and predict the absolute configuration of the two created chiral centers.3

The first application of this aldol-type asymmetric synthesis was reported by Corey during the later stages of the total synthesis of maytansine.9 This result (eq 4) showed that the t-butyl ester could be replaced by a phenyl ester as long as the same base, t-BuMgBr, is used for the condensation. The reaction of the a,b-unsaturated aldehyde gave, after desulfurization, the corresponding b-hydroxy ester in 80% yield and 86% de.

Optically active five- and six-membered lactones were also prepared by this aldol-type condensation (eq 5).10

Propargylic aldehyde was also used to prepare, by condensation with (+)-(R)-t-butyl p-tolylsulfinylacetate, a precursor of the C-3-C-8 fragment of leukotriene B4 (eq 6).11

It should be noted that a poor ee was observed during the Michael addition of (+)-(R)-t-butyl p-tolylsulfinylacetate to an a,b-unsaturated ester.12

Preparation of Sulfinyl Dienophiles.

This sulfinyl ester was also used to prepare optically active sulfinyl dienophiles by a Knoevenagel-type condensation of Glyoxylic Acid (eq 7).13,14

1. Solladié, G. S 1981, 185.
2. Solladié, G. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic: New York, 1983; Vol. 2, pp 157-198.
3. (a) Mioskowski, C.; Solladié, G. TL 1975, 3341. (b) Mioskowski, C.; Solladié, G. T 1980, 36, 227.
4. Abushanab, E; Reed, D.; Suzuki, F.; Sih, C. J. TL 1978, 3415.
5. Duñach, E.; Kagan, H. B. NJC 1985, 9, 1.
6. Mioskowski, C.; Solladié, G. CC 1977, 162.
7. Solladié, G.; Fréchou, C.; Demailly, G. NJC 1985, 9, 21.
8. Solladié-Cavallo, A.; Mioskowski, C. OMR 1981, 16, 273.
9. Corey, E. J.; Weigel, L. O.; Chamberlin, A. R.; Cho, H.; Hua, D. H. JACS 1980, 102, 6613.
10. Solladié, G.; Matloubi-Moghadam, F. JOC 1982, 47, 91.
11. Solladié, G.; Hamdouchi C., S 1991, 979.
12. Matloubi, F.; Solladié, G. TL 1979, 2141.
13. Alonso, I.; Carretero, J. C.; García Ruano, J. L. TL 1991, 32, 947.
14. Alonso, I.; Cid, M. B.; Carretero, J. C.; García Ruano, J. L.; Hoyos, M. A. TA 1991, 2, 1193.

Guy Solladié & Françoise Colobert

University Louis Pasteur, Strasbourg, France

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