Tris(pentafluorophenyl)borane-Catalyzed Formal Cyanoalkylation of Indoles with Cyanohydrins
journal contributionposted on 2021-06-02, 17:37 authored by Kensuke Kiyokawa, Naruyo Urashima, Satoshi Minakata
Despite the significant achievements related to the C3 functionalization of indoles, cyanoalkylation reactions continue to remain rather limited. We herein report on the formal C3 cyanoalkylation of indoles with cyanohydrins in the presence of a tris(pentafluorophenyl)borane (B(C6F5)3) catalyst. It is noteworthy that cyanohydrins are used as a cyanoalkylating reagent in the present reaction, even though they are usually used as only a HCN source. Mechanistic investigations revealed the unique reactivity of the B(C6F5)3 catalyst in promoting the decomposition of a cyanohydrin by a Lewis acidic activation through the coordination of the cyano group to the boron center. In addition, a catalytic three-component reaction using indoles, aldehydes as a carbon unit, and acetone cyanohydrin that avoids the discrete preparation of each aldehyde-derived cyanohydrin is also reported. The developed methods provide straightforward, highly efficient, and atom-economic access to various types of synthetically useful indole-3-acetonitrile derivatives containing α-tertiary or quaternary carbon centers.
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C 3 functionalizationcarbon unitboron centerC 3 cyanoalkylationLewis acidic activationcyanoalkylation reactionstriscyano groupacetone cyanohydrinHCN sourcealdehyde-derived cyanohydrin3 catalystthree-component reactionquaternary carbon centersMechanistic investigationscyanoalkylating reagentatom-economic accessindole -3-acetonitrile derivatives