[121221-45-2]  · C6H13NSSi  · Cyano(methylthio)methyltrimethylsilane  · (MW 159.32)

(reagent for the synthesis of a-cyano-substituted vinyl sulfides1)

Physical Data: bp 72-74 °C/4 mmHg.1

Solubility: sol ether, THF, and CHCl3.

Analysis of Reagent Purity: 1H NMR, IR.1

Preparative Method: prepared in 80-85% yield by the treatment of methylthioacetonitrile with Trimethylsilyl Trifluoromethanesulfonate and Triethylamine in ether at 0-5 °C for 3 h.1

Purification: distillation.

Handling, Storage, and Precautions: use in a fume hood.

Preparation of a-Cyano-Substituted Vinyl Sulfides.

Cyano(methylthio)methyltrimethylsilane is a Peterson alkenation reagent that was developed for the explicit purpose of preparing a-cyano-substituted vinyl sulfides in a one-step operation. Vinyl sulfides are versatile intermediates that participate in a variety of synthetically useful transformations.2

The lithiated anion of cyano(methylthio)methyltrimethylsilane reacts with aldehydes and ketones to give a-cyano-substituted vinyl sulfides directly (eq 1).1

Shown in Table 1 are representative examples that define the scope of this process. In general, cyano(methylthio)methyltrimethylsilane undergoes reaction with aromatic and nonaromatic aldehydes and ketones, and is thus useful for preparing a variety of tri- and tetrasubstituted alkenes. Longer reaction times are required in cases where steric hindrance and competitive enolization impede (entries 4-8). One limitation of the reaction is that there is a lack of stereochemical control. Reaction products are isolated as mixtures of (E) and (Z) isomers. This nonselectivity is attributed to mechanistic factors associated with the Peterson reaction.

Alternate Methods for the Preparation of a-Cyano-Substituted Vinyl Sulfides.

Numerous methods have been described for the preparation of a-cyano-substituted vinyl sulfides that vary in complexity and scope. Three approaches that require multi-step substrate modifications include the addition of methylsulfenyl chloride to acrylonitrile followed by dehydrochlorination (eq 2),3 potassium bromide induced rearrangement of a-chloro-b-alkylthionitriles (eq 3),4 and dehydrobromination of a-bromo-a-cyano thioethers (eq 4).5

In addition to cyano(methylthio)methyltrimethylsilane, two distinct reagent-based approaches to the synthesis of a-cyano-substituted vinyl sulfides have been reported. The first method involves the Horner-Emmons reaction of an aldehyde or ketone with a thiophenoxy-modified cyanomethylphosphonate (eq 5).6 This method is not of general utility since the phosphonate reagent is prepared in low yield, and its reactivity is limited by steric and electronic factors. The second method involves the condensation of ethylthioacetonitrile with an aldehyde or ketone (eq 6).5 This reaction is applicable to a variety of substrates with some limitation due to the strongly basic conditions. Products are isolated as mixtures of (E) and (Z) isomers.

1. Han, D. I.; Oh, D. Y. SC 1988, 18, 2111.
2. (a) Mignani, S.; Beaujean, M.; Janousek, Z.; Merenyi, R.; Viehe, H. G. T 1981, 37 (Suppl. 1), 111. (b) Durman, J.; Hunt, P. G.; Warren, S. TL 1983, 24, 2113. (c) Stella, L.; Boucher, J.-L. TL 1982, 23, 953.
3. Knunyants, I. L.; Lin'kova, M. G.; Kuleshova, N. D. IZV 1966, 1069.
4. (a) Gundermann, K.-D. CB 1955, 88, 1432. (b) Gundermann, K.-D.; Thomas, R. CB 1956, 89, 1263. (c) Gundermann, K.-D.; Röhrl, E. LA 1974, 1661.
5. Pochat, F. TL 1978, 2683.
6. Dinizo, S. E.; Freerksen, R. W.; Pabst, W. E.; Watt, D. S. JOC 1976, 41, 2846.

Alan D. Palkowitz, K. Jeff Thrasher, & Kenneth L. Hauser

Lilly Research Laboratories, Indianapolis, IN, USA

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