Synthesis of 2‐Substituted 3‐Alkylidene‐2,3‐dihydro‐1H‐isoindol‐1‐imines through Cyclization of [1‐(2‐Cyanophenyl)alkylidene]aminide Intermediates Generated from the Reaction of 2‐(1‐Azidoalkyl)benzonitriles with NaH

Abstract

A convenient sequence for the preparation of 3‐alkylidene‐2,3‐dihydro‐1H‐isoindol‐1‐imine derivatives 6 has been developed. Thus, 2‐(1‐azidoalkyl)benzonitriles 2, readily accessible from 2‐alkylbenzonitriles, are allowed to react with NaH in DMF at 0° to room temperature to generate [1‐(2‐cyanophenyl)alkylidene]aminide intermediates 3, of which cyclization and the subsequent rearrangement, followed by alkylation with alkyl halides, affords 2‐substituted 1‐alkylidene‐2,3‐dihydro‐1H‐isoindol‐2‐imines 6 in generally moderate yields.

Synthesis and Organocatalytic Asymmetric Nitro-aldol Initiated Cascade Reactions of 2-Acylbenzonitriles Leading to 3,3-Disubstituted Isoindolinones

“…However, 2-alkylbenzonitriles 4 are not easily accessible and few inefficient protocols are reported in literature for their synthesis. Instead of the difficult homologation of 2-methylbenzonitrile in the presence of LDA [18][19][20], we propose a new approach via reduction of 2-alkylidenebenzonitriles 6. A feature of this sequence of reactions relies on the selectivity of the Wittig reaction of the readily available 2-cyanobenzaldehyde 5 (Scheme 1), in which the cyano group in the 2 position is left non-reacted, while 2-cyanobenzaldehyde is reported to give efficient cascade reactions involving both the aldehyde and the cyano group.…”