The mechanism and sources of asymmetric induction of annulations involving acetoxy-allenoates were calculated with density functional theory (DFT). The first reported annulations of acetoxy-allenoates catalyzed by amines and phosphines were in 2010 by the Tong group. Since then, there have been numerous examples of asymmetric catalysts for these reactions, including the cinchona amines by Tong and chiral phosphines by the Fu lab. The mechanism of annulations with nucleophilic catalysis is well-understood, but annulations of acetoxy-allenoates are umpolung because the intermediate following nucleophilic addition is electrophilic rather than nucleophilic. The acetoxy-allenoate annulation mechanism has not been explored by computations and little is known about regioselectivity and the rate-controlling step. We have studied the reaction mechanism with both amines and phosphines for an achiral model system, related to the first reports of the reaction, to reveal the mechanistic pathway, the rate-determining step, and sources of regioselectivity. Following the model system, calculations of these annulations with Tong's asymmetric cinchona alkaloid-derivative and Fu's chiral phosphine were undertaken to develop a stereoselectivity model for the enantioselectivity achieved by these reactions.

Computations of stereoselectivity of asymmetric allenoate annulations

256th National Meeting (2018)

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