Synthesis of [2.2]Paracyclophane-Based Glycidic Amides Using Chiral Ammonium Ylides

An ammonium ylide-mediated stereoselective protocol for the synthesis of a series of novel [2.2]paracyclophane-based epoxides starting from racemic 4-formyl[2.2]paracyclophane has been developed. By using achiral ammonium salts as ylide precursors, the corresponding epoxide products were obtained in isolated yields up to 76 % and with diastereoselectivities up to d.r.=9 : 1. When carrying out the reaction with chiral ammonium salts instead, the products were accessible with e.r.>93.5 : 6.5 and d.r.>3 : 1, accompanied with a moderately enantioselective kinetic resolution of the racemic starting aldehyde (e.r.=75 : 25).

Automated summary

This protocol utilizes an ammonium ylide-mediated approach to achieve high yields and diastereoselectivity without the use of chiral ammonium salts, while switching to chiral salts enables high enantioselectivity and diastereoselectivity, accompanied by kinetic resolution of the racemic aldehyde starting material.