Ring Expansion and 1,2‐Migration Cascade of Benzisoxazoles with Ynamides: Experimental and Theoretical Studies

Demonstrated herein is an AuI‐catalyzed annulation of sulfonyl‐protected ynamides with substituted 1,2‐benzisoxazoles for the synthesis of E‐benzo[e][1,3]oxazine derivatives. The transformation involves the addition of benzisoxazole to the gold‐activated ynamide, ring expansion of the benzisoxazole fragment to provide an α‐imino vinylic gold intermediate, and 1,2‐migration of the sulfonamide motif to the masked carbene center to deliver the respective ring‐expanded benzo[e][1,3]oxazine of predominant E configuration. A trapping experiment justifies the participation of the α‐imino masked gold carbene. DFT computations also support the hypothesized mechanism and rationalize the product stereoselectivity. An AuI‐catalyzed annulation of sulfonyl‐protected ynamides with substituted 1,2‐benzisoxazoles for the synthesis of E‐benzo[e][1,3]oxazine derivatives is reported. The transformation involves the addition of benzisoxazole to a gold‐activated ynamide, ring expansion of the benzisoxazole fragment to provide an α‐imino vinylic gold intermediate, and 1,2‐migration of the sulfonamide motif to the masked carbene center to deliver the respective ring‐expanded benzo[e][1,3]oxazine of predominant E configuration.