(R = Me)

[5577-67-3]  · C7H19NSi  · Trimethylsilyl-t-butylamine  · (MW 145.36) (R = Et)

[17940-20-4]  · C10H25NSi  · t-Butyldimethylsilyl-t-butylamine  · (MW 187.45) (R3Si = MePh2Si)

[91308-43-9]  · C17H23NSi  · Methyldiphenylsilyl-t-butylamine  · (MW 269.50) (R3Si = t-BuMe2Si)

[93066-37-6]  · C10H25NSi  · Triethylsilyl-t-butylamine  · (MW 187.45)

(precursor of a strong, hindered base for the regioselective deprotonation of unsymmetrical ketones;1 the derived lithium amide reacts with chloromethyl ethers to give alkoxymethylamines, which can be converted to substituted t-butylamines2)

Physical Data: R = Me: bp 119 °C; n20D 1.4076; d20 0.574 g cm-3;3 pKa 33.1 (cf. 35 for dialkylamines).4 R = Et: bp 101 °C. R3Si = MePh2Si: bp 109 °C/0.4 mmHg. R3Si = t-BuMe2Si: bp 84 °C/27 mmHg.

Solubility: sol most organic solvents; reacts with protic solvents. The derived lithium trialkylsilyl-t-butylamides have solubilities similar to, or greater than, those of lithium diisopropylamide, with THF or THF/hexane being excellent solvents.

Form Supplied in: not commercially available; best prepared immediately prior to use.

Preparative Methods: these lithium reagents are prepared by the reaction of the parent amines with n-Butyllithium in THF/hexane. The parent amines are prepared by the reaction of lithium t-butylamide and the corresponding chlorosilanes (eq 1). Trimethylsilyl-t-butylamine can be prepared by the reaction of t-Butylamine and Chlorotrimethylsilane (eq 2).2,3

Purification: best purified by distillation.

Handling, Storage, and Precautions: aminosilanes react readily with protic solvents, especially water, and must be maintained in a dry environment. They are thermally stable. Use in a fume hood.

Deprotonation of Unsymmetrical Ketones.

The lithium amides of hindered amines have been employed with great success in the deprotonation of aldehydes, ketones, esters, lactones, amides, and lactams.5 In the search for greater regio- and stereoselectivity, more hindered systems have been sought.6 The trialkylsilyl-t-butylamines are readily prepared and their lithium reagents are strong bases with high regioselectivity in the deprotonation of unsymmetrical ketones. The results of a study of the deprotonation of six representative unsymmetrical ketones as outlined in eq 3 are given in Table 1.

As can be seen from the data presented in Table 1, the lithium trialkylsilyl-t-butylamides are excellent hindered bases for the stereospecific deprotonation of unsymmetrical ketones. Of particular interest is the increased ability of these bases to provide the kinetic enolate of phenylacetone, where the thermodynamic enolate benefits from the presence of the phenyl group. Also of interest is the effect of the trimethylsilyl group in Trimethylsilylacetone, where the selectivity is very high with the silylated amides as opposed to that of LDA. This effect of the trimethylsilyl group in the ketone is presumably due to the fact that the steric effect of the silyl group and its longer bond in the silyl amides better matches that of the longer C-Si bond in trimethylsilylacetone.

Preparation of Substituted t-Butylamines.

The reaction of lithium trimethylsilyl-t-butylamide with chloromethyl ethers gives alkoxymethylamines (eq 4). Organomagnesium, -aluminum, or -zinc reagents react to give nucleophilic displacement of the alkoxy group, providing substituted amines (eqs 5 and 6), which after desilylation can give substituted t-butylamines.2

Related Reagents.

Diisopropylamine; Hexamethyldisilazane.

1. Prieto, J. A.; Suarez, J.; Larson, G. L. SC 1988, 18, 253.
2. Courtois, G.; Miginiac, L. JOM 1988, 340, 127.
3. Nielson, A. J. Inorg. Synth. 1990, 27, 327.
4. Fraser, R. R.; Mansour, T. S.; Savard, S. JOC 1985, 50, 3232.
5. Stowell, J. C. Carbanions in Organic Synthesis; Wiley: New York, 1979.
6. Corey, E. J.; Gross, A. W. TL 1984, 25, 495.

Gerald L. Larson

Hüls America, Piscataway, NJ, USA

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