Preparation of Indoles from α-Aminonitriles:  A Short Synthesis of FGIN-1-27

Abstract

Alpha-Aminonitriles derived from 2-aminocinnamic acid esters and amides can be cyclized under basic conditions to furnish substituted indole-3-acetic acid derivatives in quantitative yield. The reaction provides a simple access to a class of biologically active compounds.

Synthesis of Highly Enantioenriched 3,4-Dihydroquinolin-2-ones by 6-Exo-trigRadical Cyclizations of Axially Chiral α-Halo-ortho-alkenyl Anilides

“…The synthesis of 15a is typical, and is summarized in Scheme 1. Heck reaction of 2-iodo- N ,4,6-trimethylaniline 17 16e with t -butyl acrylate under ligand-free conditions20 provided 18a in 92% yield. Acylation of 18a with chloroacetyl chloride gave α-chloro anilide 19a in 90% yield.…”

Synthesis of (–)‐(S)‐Norlaudanosine, (+)‐(R)‐O,O‐Dimethylcoclaurine, and (+)‐(R)‐Salsolidine by Alkylation of an α‐Aminonitrile

“…The resulting stabilized carbanions can be used as starting materials for the preparation of pyrrolidines, pyrroles, γ-amino acids, 1,2-diamines, or indoles in one-pot reaction procedures. [11][12][13][14][15][16] C-Alkylation of deprotonated unprotected aminonitriles 1 affords α-branched products 2, from which HCN can be eliminated to form ketimines 3. [17] Depending on the structure of the compound 3, this elimination may occur spontaneously.…”

Design and synthesis of a novel tyrosine kinase inhibitor template

“…Treatment of the resulting ester 4/5 with aldehyde 6 (made from the commercially available ester)10 using modified Opatz conditions11, 12 provided the indole ester 7/8 in 73/68% yield. Deprotection of the t -butyl ester, followed by amide coupling gave indole amide 9/10 in 80/74% overall yield.…”