Regiodivergent Opening of Phenonium Ions Derived from Strained Heterocycles and Asymmetric Intramolecular Hydroacylation for the Formation of Medium-Sized Rings

Abstract

Formation of phenonium ions through anchimeric assistance (neighboring-group participation) of aryl rings has been known since 1949. Although these reactive intermediates have been studied extensively by physical organic chemists, their potential as control elements in synthesis is underutilized. Presented herein are the first reported examples of regiodivergent openings of nonsymmetrical phenonium ions with chloride nucleophiles. The selectivity of these processes is under reagent control. The reactions are operationally simple and permit the stereospecific synthesis of complex chiral building blocks from readily accessible epoxide or aziridine starting materials. Intramolecular hydroacylation is an efficient and atom economical method for the formation of rings. The formation of chiral cyclopentanones via asymmetric hydroacylation has been extensively studied, but it remains challenging to use these methods for the formation of larger rings. To accomplish this, strategically placed heteroatoms are required to be imbedded within the starting materials. Methods for the formation of chiral medium-sized carbocyclic rings is currently unknown. Herein, I report my recent efforts to develop an asymmetric intramolecular hydroacylation reaction to form medium-sized all-carbon ring systems. Enantioselectivity is achieved using a chiral 2-aminopyridine cocatalyst.