Chemistry of Cyanide Adducts of Aldimines from Aniline Derivatives

Abstract

The chemistry of hydrogen cyanide adducts of imines is well-developed, but that of cyanide adducts remains unexplored. This is presumably because these cyanide adducts are not stable and thus not readily available in their isolated forms. In this personal account, we present the progress made in our research program towards the development of novel organic transformations utilizing cyanide adducts of imines as key intermediates. We also report the application of these methodologies to the total synthesis of natural products including indole alkaloids.

Total Syntheses of rac‐ and (+)‐Goniomitine

“…Herein we demonstrate the highly concise total syntheses of rac ‐ and (+)‐goniomitine. The cyanide‐catalyzed imino‐Stetter reaction of an aldimine derived from a 2‐aminocinnamic acid derivative and α , β ‐unsaturated aldehyde bearing the δ ‐valerolactam D‐ring at the β ‐position provided a 2‐( α ‐vinyl‐ δ ‐valerolactam) substituted indole‐3‐acetic acid derivative. Subsequent saturation of the double bond via hydrogenation provided its saturated analog.…”

Cyanide Anions as Nucleophilic Catalysts in Organic Synthesis

“…A straightforward preparation of 2,3-disubstituted indole derivative 72 has been recently developed by Cheon and co-workers. 83 Imine 71, prepared from ortho-aminocinnamate and benzaldehyde (1), is transformed with catalytic NaCN to furnish indolylacetic ester derivative 72 in 98% yield (Scheme 20). 84 Since the mechanism is related to the Stetter reaction, it was named the imino-Stetter reaction.…”

Synthesis of 2‐Substituted Tryptamines via Cyanide‐Catalyzed Imino‐Stetter Reaction

“…Our group recently developed efficient protocols for the construction of 2‐substituted indole‐3‐acetic acid derivatives via a cyanide‐catalyzed imino‐Stetter reaction of 2‐aminocinnamic acid derivatives with aldehydes [8–10] . With this protocol in hand, we envisioned that the 2‐substituted indole‐3‐acetonitrile derivatives 8 could be prepared from 2‐animocinnamyl nitriles 6 and aldehydes 7 by performing a similar imino‐Stetter reaction on the resulting aldimine intermediates 9 derived therefrom.…”