Gold-Catalyzed 1,1-Carboalkoxylation of Oxetane-Ynamides via Exocyclic Metal Carbenes: Divergent and Atom-Economical Synthesis of Tricyclic N-Heterocycles

Abstract

Transition-metal-catalyzed intramolecular carboalkoxylation of alkynes has attracted much attention in the past decades due to its high bond-forming efficiency and atom economy in the rapid assembly of functionalized cyclic compounds. However, compared with the well-established alkyne 1,2-carboalkoxylation, the related 1,1-carboalkoxylation has been far less exploited. Here, we report an unprecedented gold-catalyzed 1,1-carboalkoxylation of ynamides for the generation of exocyclic gold carbenes via exo-cyclization under room temperature. Subsequent 1,2-N-migration and 1,2-H-migration into the gold carbenes lead to the divergent and atom-economical synthesis of valuable tetrahydrofuran-fused 1,4-dihydroquinolines and furoindolines. Moreover, the asymmetric synthesis of these tricyclic N-heterocycles can be achieved by a chirality-transfer strategy, and the possibility of enantioselective cyclization via chiral gold-catalyzed kinetic resolution also emerges. In addition, the mechanistic rationale for this 1,1-carboalkoxylation, in particular accounting for the distinct migration into gold carbenes, is also strongly supported by theoretical calculations.