[121534-52-9]  · C12H26OSSi  · 1-t-Butylthio-1-t-butyldimethylsilyloxyethylene  · (MW 246.48)

(excellent reagent for Lewis acid-mediated aldol-type reactions,2 under either stoichiometric3c-e or catalytic conditions3a,b,4-6)

Physical Data: colorless liquid; bp 145 °C/20 mmHg.

Solubility: sol n-pentane, diethyl ether, dichloromethane, etc.

Analysis of Reagent Purity: (NMR) 1H 0.20 (s, 6H), 0.96 (s, 9H), 1.39 (s, 9H), 4.68 (m, 2H) ppm.

Preparative Method: the reagent is obtained by reaction of t-butyl thioacetate with Lithium Diisopropylamide in THF/HMPT and subsequent trapping with t-Butyldimethylchlorosilane (75% yield).2

Handling, Storage, and Precautions: the reagent should be stored in the absence of moisture at -15 °C.

Enantioselective Aldol Additions.1

The reagent undergoes Lewis acid-catalyzed Mukaiyama-type additions to aldehydes to give b-hydroxy thioesters with good yields and remarkable enantioselectivity (eq 1).3a,b Slow addition of the aldehyde (3-20 h) is necessary for high enantioselectivity.3a

This reaction is the catalytic version of the stoichiometric reaction outlined in eq 2.3c,d

Under the same conditions as eq 2, the reagent adds to a-keto esters to give the corresponding 2-substituted malates in good yield (74-81%) and excellent enantiomeric excesses (92-98%).3e

Other catalytic asymmetric aldol reactions are shown in eq 3. Slow addition of the aldehyde is necessary for catalyst B5 but not for A.4

Under either the catalytic (eq 1) or the stoichiometric conditions (eq 2), the reagent undergoes addition to chiral aldehydes with complete reagent control, i.e. the stereochemistry of the aldol reaction is totally controlled by the chiral catalyst regardless of the inherent diastereofacial preference of the chiral aldehydes (eq 4).6

Titanium(IV) Chloride and Tin(IV) Chloride mediate the addition of the title reagent to chiral a-alkoxy aldehydes2,7 and b-alkoxy aldehydes2 with complete chelation control (eq 5), whereas the corresponding silyl ketene acetal is unselective.1,2

Addition to Other Electrophiles.

Trimethylsilyl Trifluoromethanesulfonate catalyzes the addition to a chiral iminium ion with good yield and complete stereoselectivity (eq 6).8

Chlorotrimethylsilane-InCl3 catalyzes the addition to O-trimethylsilyl monothioacetals to afford the corresponding sulfide derivatives in good yield.9 Titanium tetrachloride mediates the addition of the title reagent to a chiral acetal with high diastereoselectivity (eq 7).10

Related Reagents.

For comparison and more details, see also those entries that deal with other silyl ketene acetals, in particular 1-t-Butylthio-1-t-butyldimethylsilyloxypropene, Ketene t-Butyldimethylsilyl Methyl Acetal, and analogs.

1. Gennari, C. COS 1991, 2, 629.
2. Gennari, C.; Cozzi, P. G. T 1988, 44, 5965.
3. (a) Kobayashi, S.; Furuya, M.; Ohtsubo, A.; Mukaiyama, T. TA 1991, 2, 635. (b) Mukaiyama, T.; Furuya, M.; Ohtsubo, A.; Kobayashi, S. CL 1991, 989. (c) Kobayashi, S.; Mukaiyama, T. CL 1989, 297. (d) Kobayashi, S.; Uchiro, H.; Fujishita, Y.; Shiina, I.; Mukaiyama, T. JACS 1991, 113, 4247. (e) Kobayashi, S.; Fujishita, Y.; Mukaiyama, T. CL 1989, 2069.
4. Mukaiyama, T.; Inubushi, A.; Suda, S.; Hara, R.; Kobayashi, S. CL 1990, 1015.
5. Parmee, E. R.; Hong, Y.; Tempkin, O.; Masamune, S. TL 1992, 33, 1729.
6. Kobayashi, S.; Ohtsubo, A.; Mukaiyama, T. CL 1991, 831.
7. Kim, S.; Salomon, R. TL 1989, 30, 6279.
8. (a) Yoshida, A.; Tajima, Y.; Takeda, N.; Oida, S. TL 1984, 25, 2793; (b) TL 1985, 26, 673.
9. Mukaiyama, T.; Ohno, T.; Nishimura, T.; Han, J. S.; Kobayashi, S. CL 1990, 2239.
10. Mori, I.; Ishihara, K.; Flippin, L. A.; Nozaki, K.; Yamamoto, H.; Bartlett, P. A.; Heathcock, C. H. JOC 1990, 55, 6107.

Cesare Gennari

Università di Milano, Italy

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.