Synthesis of Benzoisochromene Derivatives via C–H Activation-Initiated Cascade Formal [4+2] and [2+4] Annulation of Aryl Enaminone with Vinyl-1,3-dioxolan-2-one

Abstract

Cascade annulation reactions can assemble structurally intricate polycyclic molecules from simple starting materials with enhanced efficiency and minimized production of waste. Presented herein is a concise and effective synthesis of benzoisochromene derivatives based on a C-H activation-initiated cascade formal [4+2]/[2+4] annulation of aryl enaminone with vinyl-1,3-dioxolan-2-one. In constructing the six-membered carbocycle, aryl enaminone acted as the C4 synthon while vinyl-1,3-dioxolan-2-one acted as the C2 synthon. In constructing the six-membered <i>O</i>-heterocycle, on the other hand, the former acted as C2 synthon while the latter acted as C3O1 synthon. To our knowledge, this is the first simultaneous construction of both a carbocycle and an <i>O</i>-heterocycle via concurrent C-H/C-N/C-O bond cleavage and C-C/C-C/C-O bond formation. In general, this novel protocol features the use of readily obtainable substrates of broad scope, excellent atom- and step-economy, intriguing reaction pathway, and valuable products.