Neutral π-Nucleophile-Catalyzed Cyanation of Aldehydes and Ketones

Abstract

1-Methoxy-2-methyl-1-(trimethylsiloxy)propene, a neutral π-nucleophile, was found to be able to efficiently catalyze the cyanation (cyanosilylation and cyanocarbonation) of various aldehydes and ketones, and this study provided the first illustration of using a neutral π-nucleophile for the development of synthetically useful organocatalysis.

Key words

π-nucleophile - cyanosilylation - cyanocarbonation - aldehydes - ketones

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12

General Procedure
A mixture of aldehyde or ketone 1a-s (0.50 mmol), TMSCN (0.60-0.75 mmol) and catalyst 3j (1-15 mol%) was allowed to stand in a vial at 16-50 °C (indicated in Table [2] ). The reaction was monitored by GC or TLC. After the aldehyde or ketone was completely consumed, the reaction mixture was subject to a reduced pressure of 5-10 mmHg at 25-50 °C to remove catalyst 3j and the remaining TMSCN, and the desired product 2a-s was obtained in quantitative yield. Cyanohydrin silyl ethers 2a-s are known compounds, see ref. 8-10.

13

The boiling point of catalyst 3j is 57 °C/15 mmHg, and that of TMSCN is 118 °C.

14

For previously reported methods, the extractive procedures and/or column chromatography are needed to purify the products. See references 7-10, and references cited therein.

17

No significant IR change was observed for benzaldehyde (or ethyl cyanoformate) with the addition of catalyst 3j.

18

Based on its π-nucleophilicity, we speculate that catalyst 3j may activate the cyanating agent with its π-system through association. However, to our knowledge, this type of π-based catalysis has not been reported previously.