[23184-28-3]  · C7H17NOSi  · N,N-Dimethyl-2-(trimethylsilyl)acetamide  · (MW 159.34)

(preparation of a,b-unsaturated amides,1 b-enamino amides,2 and g-trimethylsiloxy amides3)

Physical Data: bp 67-69 °C/4 mmHg; 47-49 °C/0.2 mmHg.

Preparative Methods: although the direct trimethylsilylation of the lithium enolate of N,N-dimethylacetamide3a is the most straightforward approach to the title reagent, other a-silyl amides have been prepared by amidation of the corresponding esters.4 The reaction of aminosilanes with ketene gives the O-trimethylsilylated isomer, which thermally rearranges to the a-trimethylsilylamide.5 In reactions of chlorosilanes with the lithium enolates of amides, larger silyl groups such as the t-butyldimethylsilyl group tend towards O-silylation, and smaller groups on nitrogen lead to C-silylation.3a Thermal isomerization leads to the C-silylated tautomer as the major product (eq 1). The direct C-dimethylphenylsilylation of the lithium enolate of N-methyl-d-valerolactam has been reported (eq 2).6

Preparation of a,b-Unsaturated Amides.

Reaction of N,N-dimethyl-2-(trimethylsilyl)acetamide with either Lithium Diisopropylamide or n-Butyllithium in THF at 0 °C provides the lithium enolate, which is stable at rt for several days. This enolate reacts with aldehydes and ketones to produce a,b-unsaturated amides via the condensation-Peterson elimination sequence (eq 3). This reaction was employed in an approach to (±) cherylline (eq 4).7

The reaction of the lithium enolate of N,N-dimethyl-2-(trimethylsilyl)acetamide with aromatic nitrones gives a-aryl-a,b-unsaturated amides in modest yields (eq 5).8 The reaction of the lithium enolate with amides yields b-amino-a,b-unsaturated amides (eq 6),2 and the reaction with propene oxide leads to N,N-dimethyl-4-(trimethylsiloxy)pentanamide (eq 7).1

Other Applications.

The direct a-trimethylsilylation of b-lactams and the intermediates used in the synthesis of this important class of compounds have been reported.9

Related Reagents.

t-Butyl Trimethylsilylacetate; Ethyl 2-(Methyldiphenylsilyl)propanoate; Ethyl Trimethylsilylacetate; Trimethylsilylacetic Acid; Trimethylsilylacetone.

1. Woodbury, R. P.; Rathke, M. W. JOC 1978, 43, 1947.
2. Woodbury, R. P.; Rathke, M. W. TL 1978, 709.
3. (a) Woodbury, R. P.; Rathke, M. W. JOC 1978, 43, 881. (b) Hudrlik, P. F.; Peterson, D.; Chou, D. SC 1975, 5, 359. (c) Urayama, S.; Inoue, S.; Sato, Y. JOM 1988, 354, 155.
4. Maslii, L. K.; Dobroserdova, I. L. ZOB 1967, 37, 2554.
5. Lutsenko, I. F.; Baukov, Yu. I.; Kostyuk, A. S.; Savelyeva, N. I.; Krysina, V. K. JOM 1969, 17, 241.
6. Trost, B. M.; Kunz, R. A. JOC 1974, 39, 2475.
7. Hart, D. J.; Cain, P. A.; Evans, D. A. JACS 1978, 100, 1548.
8. Tsuge, O.; Sone, K.; Urano, S.; Matsuda, K. JOC 1982, 47, 5171.
9. (a) Fritz, H.; Sutter, P.; Weis, C. D. JOC 1986, 51, 558. (b) Bergmann, H. J.; Mayrhofer, R.; Otto, H. H. AP 1986, 319, 203. (c) Cossio, F. P.; Odriozola, J. M.; Oiarbide, M.; Palomo, C. CC 1989, 74.

Gerald L. Larson

Hüls America, Piscataway, NJ, USA

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