Tuneable access to isoquinolines via a transition-metal-free C(sp3)–C(sp3) bond cleavage rearrangement reaction

Abstract

A tuneable route to multi-substituted isoquinolines through C–C bond cleavage from ethyl-3-benzyl-3,4-dihydroisoquinoline-3-carboxylate derivatives has been developed. Sodium hydride promoted the formation of 1-(isoquinolin-3-yl)-2-phenylethan-1-ones through a novel rearrangement involving C–C bond cleavage and the formation of a new C–C bond. When ethyl-3-benzyl-3,4-dihydroisoquinoline-3-carboxylates were treated with N-bromosuccinimide, ethyl isoquinoline-3-carboxylates were selectively formed via a radical pathway. These reactions proceed smoothly in moderate to excellent yields under transition-metal-free conditions, and a wide range of functional groups are tolerated.