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

• Published in: ACS catalysis 2021-03, Vol.11 (6), p.3679-3686
• Main Authors: Qi, Lin-Jun, Shi, Chong-Yang, Chen, Peng-Fei, Li, Long, Fang, Gang, Qian, Peng-Cheng, Deng, Chao, Zhou, Jin-Mei, Ye, Long-Wu
• Format: Article
• Language: English
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.1c00461

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.