Computationally Designed Dearomative Claisen-Type Rearrangement of a Benzyl Alkynyl Ether and Cascade Reaction To Provide a Dihydroindenone

Computer-aided substrate design is an effective approach to developing new reactions. Here, we report the dearomative Claisen-type rearrangement along with the construction of a quaternary carbon via comprehensive evaluation of the transition states of virtual substrates. The experimental rearrangement of 2,4,6-trimethyl benzyl alkynyl ether occurs as designed. Serendipitously, the rearrangement is followed by cyclization to the 3/4/6-tricyclic system and opening of the four-membered ring accompanied by methyl group migration to afford a dihydroindenone derivative.