(1; R1 = Me, R2 = t-Bu)

[41879-39-4]  · C6H17NOSi  · O-(t-Butyldimethylsilyl)hydroxylamine  · (MW 147.29) (2; R1 = R2 = Me)

[22737-36-6]  · C3H11NOSi  · O-(Trimethylsilyl)hydroxylamine  · (MW 105.21) (3; R1 = Ph, R2 = t-Bu)

[103587-51-5]  · C16H21NOSi  · O-(t-Butyldiphenylsilyl)hydroxylamine  · (MW 271.43)

(preparation of O-silyloximes;1 generation of nitrosoalkenes;1,2 generation of azadienes3)

Physical Data: (1) mp 62-65 °C; bp 87-90 °C/40 mmHg. (2) bp 98-100 °C; d 0.860 g cm-3. (3) mp 74-75 °C; bp 175 °C/0.6 mmHg.

Solubility: freely sol hexane, chloroform, and most organic solvents; insol water.

Form Supplied in: colorless solid or liquid; commercially available.

Preparative Methods: the reagents are most conveniently prepared by treatment of Hydroxylamine hydrochloride with ethylenediamine in dichloromethane, followed by the appropriate chlorosilane.4 A two-step procedure using ammonia in place of ethylenediamine has also been reported.1

Purification: reagents are purified via distillation and/or recrystallization (>97% GC).

Handling, Storage, and Precautions: O-silylhydroxylamines should be protected from moisture and handled in a fume hood.

Preparation of O-Silyloximes and Oximes.

O-Silylhydroxylamines are used to prepare O-silyloximes via treatment of carbonyl compounds with these reagents in CHCl3 in the presence of 4 Å molecular sieves.1 Treatment of O-silyloximes with fluoride ion yields the desilylated oximes, thus allowing the oximation of acid- or base-sensitive ketones and aldehydes.

A series of 3-alkyl-2-chlorocyclohexanone silyloximes (methyl, ethyl, i-propyl) have been prepared and their conformations extensively examined.5 By analysis of the vicinal interproton coupling, these compounds were shown to exist predominantly in the diaxial chair conformation (5) while the precursor ketones prefer the diequatorial conformation (4). This observation was corroborated by an X-ray crystal structure of trans-3-methyl-2-chlorocyclohexanone t-butyldiphenylsilyloxime, which showed that the chair with diaxial substituents is indeed preferred in the solid state. A strong hyperconjugative stabilization of the axial conformation, termed the vinylogous anomeric effect, was proposed to be the origin of this preference.

Generation of Nitrosoalkenes.

Treatment of silyloximes of a-halocarbonyl compounds with fluoride ion generates nitrosoalkenes without extraneous nucleophilic species present.1 Nitrosoalkenes generated from (6) have been used in intramolecular [4 + 2] cycloadditions (eq 1).2 Electron-rich alkenes are required for concerted cycloadditions as this is an inverse electron-demand cycloaddition. The choice of fluoride source is critical for success in that the highest yields are obtained when the nitrosoalkene is slowly generated via use of sparingly soluble metal fluorides such as Cesium Fluoride or Potassium Fluoride.

Generation of 1-Azadienes.

O-Silyloximes have also been used to generate 1-azadienes for [4 + 2] cycloadditions.3 Thus an O-silyloxime of an a,b-unsaturated aldehyde can be treated with an acid chloride or chloroformate in the presence of Chlorotrimethylsilane and Aluminum Chloride to give an a-cyanohydroxamic acid derivative, which upon mild thermolysis forms an azadiene (eq 2). These azadienes undergo efficient intermolecular [4 + 2] cycloadditions or, with an tethered alkene, intramolecular cycloadditions.

Reactions at the Hydroxylamine Nitrogen.

These reagents have been used as O-protected forms of hydroxylamine for synthetic transformations involving the unprotected nitrogen. Thus O-silylhydroxylamines have been used to prepare N-hydroxy-b-lactams6 and substituted dihydro-3-hydroxy-1,2,3-benzotriazines,7 as well as N-alkylated hydroxylamines for use as leukotriene biosynthesis inhibitors.8

Related Reagents.

O-Benzylhydroxylamine Hydrochloride; N,O-Bis(trimethylsilyl)hydroxylamine; Hydroxylamine; O-(Mesitylsulfonyl)hydroxylamine.

1. Denmark, S. E.; Dappen, M. S. JOC 1984, 49, 798.
2. Denmark, S. E.; Dappen, M. S.; Sternberg, J. A. JOC 1984, 49, 4741.
3. Teng, M.; Fowler, F. W. JOC 1990, 55, 5646.
4. Bottaro, J. C.; Bedford, C. D.; Dodge, A. SC 1985, 15, 1333.
5. Denmark, S. E.; Dappen, M. S.; Sear, N. S.; Jacobs, R. T. JACS 1990, 112, 3466.
6. Zercher, C. K.; Miller, M. J. TL 1989, 50, 7009.
7. Jakobsen, M. H.; Buchardt, O.; Holm. A.; Meldal, M. S 1990, 1008.
8. Stewart, A. O.; Martin, J. G. JOC 1989, 54, 1221.

Michael S. Dappen

Athena Neurosciences, South San Francisco, CA, USA

Scott E. Denmark

University of Illinois, Urbana, IL, USA

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