We report an enantioselective oxidative C-N bond forming reaction to produce 1,2,3,4-tetrahydroisoquinoline-derived cyclic aminals using a cationic oxoammonium salt as the stoichiometric oxidant. Central to the success of this goal was the design of a library of axially chiral BINOL-based phosphoric acids bearing differentially substituted triazoles at the 3 and 3' positions to assist in transition state organization in the enantio-determining step by forming attractive interactions with the amide-containing substrate. This novel class of phosphoric acids was shown to significantly outperform a range of conventional ones bearing aryl groups at these positions. Our recent efforts suggest that it is the special electronic properties of the triazole substituents that underlie this superior selectivity.  We believe that this work offers an alternative to the conventional strategy of increasing catalyst steric bulk to improve difficult enantioselective transformations.

Asymmetric cross dehydrogenative coupling enabled by the design of chiral triazole-containing phosphoric acids: Reaction development and mechanistic insights

248th National Meeting (2014)

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