[107-14-2]  · C2H2ClN  · Chloroacetonitrile  · (MW 75.50)

(reagent for two-carbon homologation of alkenes via organoboranes;1 useful in Wittig alkenation of ketones2 and Darzens condensations3)

Physical Data: bp 124-126 °C; d 1.193 g cm-3.

Form Supplied in: colorless liquid, widely available.

Handling, Storage, and Precautions: highly toxic and a lachrymator; use in a fume hood.

Homologation of Alkenes via Organoboranes.

Organoboranes undergo a base-induced reaction with a variety of a-halo esters, ketones, and nitriles.4 The reaction substitutes the a-halogen with an alkyl group from boron (eq 1).

The use of 9-Borabicyclo[3.3.1]nonane provides for efficient use of the alkyl group on boron.1 The two chlorines of dichloroacetonitrile may be successively replaced (eq 2).

The reaction proceeds with retention of configuration of the original boron-carbon bond. This feature has been used for the stereoselective construction of steroid side chains (eq 3).5,6

Either the natural or unnatural C-20 stereochemistry may be obtained (eq 4), depending on the configuration of the ethylidene unit.

Wittig Alkenation of Ketones.

Ketones may be converted into a,b-unsaturated nitriles through a modified Wittig-Horner-Emmons reaction (eq 5).2 The (E) isomer predominates.

Darzens Condensations.

Glycidonitriles may be obtained by treating ketones with chloroacetonitrile and base (eq 6).3 These glycidonitriles may be rearranged to carboxylic acids (eq 7).

Related Reagents.

Dichloroacetonitrile; Iodoacetonitrile; Methyl Bromoacetate; Methyl Chloroacetate.

1. Brown, H. C.; Nambu, H.; Rogic, M. M. JACS 1969, 91, 6854.
2. Loupy, A.; Gogadji, K.; Seyden-Penne, J. S 1977, 126.
3. White, D. R.; Wu, D. K. CC 1974, 988.
4. Brown, H. C.; Rogic, M. M. Organomet. Chem. Synth. 1972, 1, 305.
5. Midland, M. M.; Kwon, Y. C. JOC 1981, 46, 1227.
6. Midland, M. M.; Kwon, Y. C. TL 1982, 23, 2077.

M. Mark Midland

University of California, Riverside, CA, USA

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