Parallel synthesis of 2,4,5-trisubstituted thiophene-3-carbonitrile derivatives on traceless solid support

Abstract

A parallel solid-phase synthesis of 2,4,5-trisubstituted thiophene-3-carbonitrile derivatives was developed. The polymer-supported synthetic route progressed using the sulfide linker via a traceless strategy. The initial synthesis utilized the Thorpe-Ziegler type cyclization of alpha-haloketone and polymer-supported 2,2-dicyanoethene-1,1-bis(thiolate), which was derived from the Merrifield resin. The resulting thiophene resin was introduced to one substitution by N-arylation. After oxidation of sulfides to sulfones in the thiophene resins for subsequent cleavage, nucleophilic desulfonative substitution with amines and thiols afforded the desired thiophene-3-carbonitrile derivatives in good overall yields. (C) 2014 Elsevier Ltd. All rights reserved.