t-Butyl Trimethylsilylacetate

[41108-81-0]  · C9H20O2Si  · t-Butyl Trimethylsilylacetate  · (MW 188.34)

(used to prepare lithium enolates which can be alkylated;1,2 can be alkenated with aldehydes and ketones;3 can be acylated;4 can be reacted with Group 14 halides5)

Physical Data: air stable, colorless liquid; bp 67 °C/13 mmHg; n20D 1.4184; 1H NMR (CDCl3, 90 MHz) 0.13 (s, 9H), 1.45 (s, 9H), 1.80 (s, 2H); IR 1710 cm-1.

Preparative Methods: an advantage of t-butyl trimethylsilylacetate over its methyl and ethyl ester analogs is that it can be prepared by C-silylation of the lithium enolate of t-butyl acetate at -78 °C in THF (85-90% yield). Under the same conditions the enolates of methyl and ethyl acetate give primarily O-silylated products.3 The reagent has also been prepared by a rapid Boron Trifluoride Etherate catalyzed reaction of Trimethylsilylketene with t-butyl alcohol.6

Lithium Enolate.

Most applications require initial formation of the enolate (1) (eq 1), which is obtained as a white solid suspended in THF, stable indefinitely at -78 °C.1

Alkylation Reactions.

Enolate (1) is readily alkylated with a variety of primary alkyl halides at -70 to 0 °C in THF,2,7 usually in the presence of TMEDA or DMSO. The alkylation products may be desilylated (eq 2) to provide a two-carbon chain extension which is not prone to dialkylation or elimination side reactions.7a

The reagent is spiroalkylated in two steps with 2-methyl-1,4-diiodobutane (eq 3).7b

Enolate (1) can be vinylated with 2-bromopropene in the presence of a Ni catalyst.7c

Peterson Alkenation.8

Enolate (1) reacts with aldehydes or ketones to give a,b-unsaturated esters (eq 4).1,8 In some cases (1) gives better yields and different E:Z ratios from the analogous Horner-Emmons reactions with phosphonoacetates.9

Reaction with Acyl Derivatives.

Enolate (1) does not react with ethyl acetate or N,N-dimethylacetamide, and gives a complicated mixture of products with acetyl chloride. However, (1) is acetylated with acetylimidazole to give the lithium enolate of t-butyl acetoacetate (eq 5).4a

Protonation of the reaction mixtures obtained with a variety of acylimidazoles gives b-keto esters in 50-94% yields. Enolate (1) reacts with a variety of lactones to give Peterson alkenation products (eq 6).4b

Enolate (1) reacts with some aromatic nitriles (but not with benzonitrile) to give N-silylenamines.10

Reaction with Group 14 Halides.

Enolate (1) reacts with Chlorotrimethylgermane or Tri-n-butylchlorostannane to give t-butyl (trimethylgermyl)(trimethylsilyl)acetate (83% yield)5a and t-butyl (trimethylsilyl)(tri-n-butylstannyl)acetate,5b respectively.

Related Reagents.

t-Butyl a-Lithiobis(trimethylsilyl)acetate; Ethyl Lithioacetate; Ethyl Lithio(trimethylsilyl)acetate; Ethyl Trimethylsilylacetate; Triethyl Phosphonoacetate; Trimethylsilylacetic Acid.

1. Hartzell, S. L.; Sullivan, D. F.; Rathke, M. W. TL 1974, 15, 1403.
2. Hudrlik, P. F.; Peterson, D.; Chou, D. SC 1975, 5, 359.
3. Rathke, M. W.; Sullivan, D. F. SC 1973, 3, 67.
4. (a) Hartzell, S. L.; Rathke, M. W. TL 1976, 2757. (b) Saúve, G.; Deslongchamps, P. SC 1985, 15, 201.
5. (a) Kanemoto, N.; Sato, Y.; Inoue, S. JOM 1988, 348, 25. (b) Ager, D. J.; Cooke, G. E.; East, M. B.; Mole, S. J.; Rampersaud, A.; Webb, V. J. OM 1986, 5, 1906.
6. Ruden, R. A. JOC 1974, 39, 3607.
7. (a) Helmchen, G.; Schmierer, R. TL 1983, 24, 1235. (b) Paquette, L. A.; Maynard, G. D.; Ra, C. S.; Hoppe, M. JOC 1989, 54, 1408. (c) Chenera, B.; Chuang, C-P.; Hart, D. J.; Lai, C-S. JOC 1992, 57, 2018. (d) Heathcock, C. H.; Piettre, S.; Ruggeri, R. B.; Ragan, J. A.; Kath, J. C. JOC 1992, 57, 2554.
8. For reviews see: Ager, D. J. S 1984, 384; OR 1990, 38, 1.
9. (a) Crimmin, M. J.; O'Hanlon, P. J.; Rogers, N. H. JCS(P1) 1985, 541. (b) Budhram, R. S.; Palaniswamy, V. A.; Eisenbraun, E. J. JOC 1986, 51, 1402. (c) Rosen, G. M.; Rauckman, E. J. OPP 1978, 10, 17. (d) Duraisamy, M.; Walborsky, H. M. JACS 1983, 105, 3252. (e) Bennett, M.; Gill, G. B.; Pattenden, G.; Shuker, A. J. SL 1990, 455.
10. Konakahara, T.; Kurosaki, Y. JCR(S) 1989, 130.

Michael Rathke & Robert Elghanian

Michigan State University, East Lansing, MI, USA

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