Diastereoselective Synthesis of Tetrahydroquinolines through a Multi-component Aza-Prins-Ritter Reaction Sequence.

Abstract

A series of substituted tetrahydroquinoline (THQ) derivatives were synthesized via a triflic acid-promoted multicomponent aza-Prins-Ritter reaction of 2-(tosylamino)styrenes with carbonyl compounds and substituted acetonitriles, the latter serving as both solvent and nucleophile. The reaction proceeds under mild conditions and exhibits broad substrate scope and excellent functional group tolerance. A wide range of aryl, heteroaryl, and alkyl aldehydes, as well as symmetric ketones, were compatible. Additionally, different nitriles and substituted 2-(tosylamino)styrenes enabled access to the synthesis of diverse substituted THQs. Orthogonal deprotection of the N-acetyl and N-tosyl groups furnished the corresponding free amines, highlighting the synthetic utility of this methodology.