[102146-11-2]  · C13H28OSSi  · 1-t-Butylthio-1-t-butyldimethylsilyloxypropene  · (MW 260.51) (E)

[97250-84-5] (Z)


(excellent reagent for Lewis acid-mediated aldol-type2-9 and Michael additions,17-21 under either stoichiometric or catalytic conditions)

Physical Data: colorless liquid.

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

Analysis of Reagent Purity: (NMR) 1H 0.15 (s, 6H), 0.95 (s, 9H), 1.30 (s, 9H), 1.65 (d, 3H, J = 6.7 Hz), 5.22 (q, 1H, J = 6.7 Hz) ppm (Z isomer). 1H 0.18 (s, 6H), 0.95 (s, 9H), 1.30 (s, 9H), 1.60 (d, 3H, J = 6.8 Hz), 5.22 (q, 1H, J = 6.8 Hz) ppm (E isomer).

Preparative Methods: obtained by reaction of t-butyl thiopropionate with Lithium Diisopropylamide in THF and subsequent trapping with t-Butyldimethylsilyl Trifluoromethanesulfonate (95% Z isomer),2 or with LDA in THF/HMPT and subsequent trapping with t-Butyldimethylchlorosilane (95% E isomer).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 syn a-methyl-b-hydroxy thioesters with good yields and remarkable enantioselectivities (eq 1).3a-d Slow addition of the aldehyde (3-4.5 h) in propionitrile is necessary for high enantioselectivity.3b-d

A similar version of the reaction makes use of 100 mol % tin(II) oxide, 65 mol % Trimethylsilyl Trifluoromethanesulfonate, and 50 mol % chiral diamine under slow addition conditions (9 h), with slightly worse results (58-82% yield; syn:anti = 91:9-98:2; 68-94% ee).3e These reactions are the catalytic versions of the stoichiometric reaction outlined in eq 2.3c,3d,3f-i

Under similar conditions to eq 2, the reagent adds to a-keto esters to give the corresponding substituted malates in good yield and high stereoselectivity (eq 3).3j

Under similar conditions to eq 3, silyl ketene acetals derived from a-benzyloxy thioesters4a-c or a-silyloxy thioesters4d add to various aldehydes to give either anti (91-99%) or syn (88-97%) a,b-dihydroxy thioesters, depending on the reagent used, in good yield (46-93%) and with high enantioselectivity (82-98% ee).

Another catalytic asymmetric aldol reaction is shown in eq 4. Slow addition of the aldehyde is again necessary for high selectivity.5 Catalyst A is preferred in reactions with aromatic and unsaturated aldehydes, while catalyst B is employed in reactions with primary aldehydes.5 In contrast to the catalysts mentioned above (eqs 1-3), both A and B give anti aldols as the predominant stereoisomers.5

Diastereoselective Aldol Additions.1

Boron Trifluoride Etherate mediates the addition of both (E) and (Z) title reagents to various aldehydes to give the aldol products with high anti selectivity (anti:syn = 91:9-96:4) irrespective of the silyl ketene acetal geometry (eq 5).2,6 Syn selectivity is obtained using the (E) isomer via fluoride-mediated addition to benzaldehyde (syn:anti = 95:5),2 or via TMSOTf-catalyzed addition to benzaldehyde dimethyl acetal (syn:anti = 78:22).7a-d Titanium(IV) Chloride mediates the addition of both (E) and (Z) title reagents to propynals to give the aldol products with high anti selectivity (anti:syn &egt; 95:5) irrespective of the silyl ketene acetal geometry, while high syn selectivity (syn:anti &egt; 98:2) is obtained in the TiCl4-mediated addition to cobalt-complexed propynals.7e High syn selectivity is obtained in the uncatalyzed reaction of either (E)- or (Z)-O-silacyclobutyl analogs via a direct silicon group transfer (eq 5).8

Simple stereoselectivity (syn:anti ratios) can be controlled in the Sn(OTf)2-mediated addition of the reagent to a-keto esters by varying the silyl ketene acetal geometry (eq 6).3j

The reagent undergoes Lewis acid-promoted Mukaiyama-type additions1 to chiral aldehydes with moderate to good stereocontrol (eq 7).2,6,9a-d It is remarkable that high diastereoselectivity (>99%) can be obtained using TiCl4 due to chelation control, and that these results are independent of the silyl ketene acetal geometry.2,9b These reactions have been used for establishing three consecutive stereocenters in the total synthesis of several biologically interesting compounds.10-13

Addition to Other Electrophiles.

Zinc Chloride catalyzes the addition to a chiral azetinone with good yield. The stereochemical outcome depends on the sulfur substituent (eq 8).14

TiCl4 mediates the addition of the title reagents to achiral and chiral thionium ions with good diastereoselectivity (eq 9).15

Tin(IV) Chloride or BF3.OEt2 mediate the addition of the title reagents to norephedrine-derived 2-methoxyoxazolidines; yields and diastereomeric ratios are independent of the silyl ketene acetal geometry (eq 10).16

Michael Additions.

In the presence of a catalytic amount of trityl salts (2-3 mol %), thioester silyl ketene acetals react stereoselectively with acyclic a,b-unsaturated ketones to give the Michael adducts in high yield (eq 11).17a

In the case of cyclic ketones, either the syn or the anti products can be obtained stereoselectively by varying catalyst and substituents (eq 12).17a,b For high syn selectivity the t-butyl thioester group (R2 = t-Bu) is essential, while both the substituent on silicon (R3) and silyl ketene acetal geometry have little effect on the diastereoselectivity.17b

Catalytic amounts (5 mol %) of trityl chloride and Tin(II) Chloride,18 or Antimony(V) Chloride and tin(II) triflate,19 have also been used to promote the Michael additions, with stereoselectivity in favor of the anti isomers and slightly reduced ratios in comparison with the above results. No stereoselectivity was observed with catalytic amounts (10 mol %) of Ytterbium(III) Trifluoromethanesulfonate.20

Using the Michael-aldol protocol, several key intermediates on the way to natural products have been synthesized, e.g. dehydroiridodiol,17a aromatin,17b and fastigilin-C (eq 13).21

Related Reagents.

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

1. Gennari, C. COS 1991, 2, 629.
2. Gennari, C.; Beretta, M. G.; Bernardi, A.; Moro, G.; Scolastico, C.; Todeschini, R. T 1986, 42, 893.
3. (a) Mukaiyama, T.; Kobayashi, S.; Uchiro, H.; Shiina, I. CL 1990, 129. (b) Kobayashi, S.; Fujishita, Y.; Mukaiyama, T. CL 1990, 1455. (c) Kobayashi, S.; Uchiro, H.; Shiina, I.; Mukaiyama, T. T 1993, 49, 1761. (d) Mukaiyama, T.; Furuya, M.; Ohtsubo, A.; Kobayashi, S. CL 1991, 989. (e) Mukaiyama, T.; Uchiro, H.; Kobayashi, S. CL 1990, 1147. (f) Mukaiyama, T.; Uchiro, H.; Kobayashi, S. CL 1989, 1757. (g) Mukaiyama, T.; Asanuma, H.; Hachiya, I.; Harada, T.; Kobayashi, S. CL 1991, 1209. (h) Mukaiyama, T.; Uchiro, H.; Kobayashi, S. CL 1989, 1001. (i) Kobayashi, S.; Uchiro, H.; Fujishita, Y.; Shiina, I.; Mukaiyama T. JACS 1991, 113, 4247. (j) Kobayashi, S.; Hachiya, I. JOC 1992, 57, 1324.
4. (a) Mukaiyama, T.; Uchiro, H.; Shiina, I.; Kobayashi, S. CL 1990, 1019. (b) Mukaiyama, T.; Shiina, I.; Kobayashi, S. CL 1990, 2201. (c) Kobayashi, S.; Onozawa, S.; Mukaiyama, T. CL 1992, 2419. (d) Mukaiyama, T.; Shiina, I.; Kobayashi, S. CL 1991, 1901.
5. Parmee, E. R.; Hong, Y.; Tempkin, O.; Masamune, S. TL 1992, 33, 1729.
6. Gennari, C.; Bernardi, A.; Cardani, S.; Scolastico, C. TL 1985, 26, 797.
7. (a) Murata, S.; Suzuki, M.; Noyori, R. JACS 1980, 102, 3248. (b) Noyori, R.; Murata, S.; Suzuki, M. T 1981, 37, 3899. (c) Murata, S.; Noyori, R. TL 1982, 23, 2601. (d) Murata, S.; Suzuki, M.; Noyori, R. T 1988, 44, 4259. (e) Mukai, C.; Kataoka, O.; Hanaoka, M. TL 1991, 32, 7553.
8. Denmark, S. E.; Griedel, B. D.; Coe, D. M. JOC 1993, 58, 988.
9. (a) Gennari, C.; Bernardi, A.; Poli, G.; Scolastico, C. TL 1985, 26, 2373. (b) Gennari, C.; Bernardi, A.; Scolastico, C.; Potenza, D. TL 1985, 26, 4129. (c) Annunziata, R.; Cinquini, M.; Cozzi, F.; Cozzi, P. G.; Consolandi, E. JOC 1992, 57, 456. (d) Yamazaki, T.; Yamamoto, T.; Kitazume, T. JOC 1989, 54, 83.
10. Gennari, C.; Cozzi, P. G. JOC 1988, 53, 4015.
11. Pilli, R. A.; Murta, M. M. JOC 1993, 58, 338.
12. Dìez-Martin, D.; Kotecha, N. R.; Ley, S. V.; Mantegani, S.; Menéndez, J. C.; Organ, H. M.; White, A. D. T 1992, 48, 7899.
13. Rosemberg, S. H.; Boyd, S. A.; Mantei, R. A. TL 1991, 32, 6507.
14. (a) Martel, A.; Daris, J.-P.; Bachand, C.; Corbeil, J.; Menard, M. CJC 1988, 66, 1537. See also: (b) Shibata, T.; Iino, K.; Tanaka, T.; Hashimoto, T.; Kameyama, Y.; Sugimura, Y. TL 1985, 26, 4739. (c) Kim, C. U.; Luh, B.; Partyka, R. A. TL 1987, 28, 507.
15. Mori, I.; Bartlett, P. A.; Heathcock, C. H. JOC 1990, 55, 5966.
16. (a) Bernardi, A.; Cardani, S.; Carugo, O.; Colombo, L.; Scolastico, C.; Villa, R. TL 1990, 31, 2779. (b) Bernardi, A.; Cavicchioli, M.; Poli, G.; Scolastico, C.; Sidjimov, A. T 1991, 47, 7925.
17. (a) Mukaiyama, T.; Tamura, M.; Kobayashi, S. CL 1986, 1817. (b) Mukaiyama, T.; Tamura, M.; Kobayashi, S. CL 1987, 743.
18. Mukaiyama, T.; Kobayashi, S.; Tamura, M.; Sagawa, Y. CL 1987, 491.
19. Kobayashi, S.; Tamura, M.; Mukaiyama, T. CL 1988, 91.
20. Kobayashi, S.; Hachiya, I.; Takahori, T.; Araki, M.; Ishitani, H. TL 1992, 33, 6815.
21. (a) Tanis, S. P.; McMills, M. C.; Scahill, T. A.; Kloosterman, D. A. TL 1990, 31, 1977. (b) Tanis, S. P.; Robinson, E. D.; McMills, M. C.; Watt, W. JACS 1992, 114, 8349.

Cesare Gennari

Università di Milano, Italy

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