Chemodivergent Preparation of Various Heterocycles via Phase‐Transfer Catalysis: Enantioselective Synthesis of Functionalized Piperidines

In this work, a new chemodivergent domino approach for the preparation of various saturated heterocycles, based on phase‐transfer catalysis (PTC), is presented. The versatile nature of doubly electrophilic substrates, showing both a Michael acceptor and a ketone, tethered by a heteroatom, enables three different domino reaction pathways. The nucleophile dictates the chemoselectivity of the reaction. Sulfa‐Michael/aldol, cyanide addition/oxa‐Michael and Michael/H‐shift/aldol processes, along with the variation of the tethering heteroatom, results in the formation of six different classes of saturated heterocycles. DFT calculations account for the observed chemo‐ and diastereoselectivity of the two most productive processes. Moreover, an extensive investigation on the sulfa‐Michael/aldol pathway was carried out, ultimately leading to the development of a new enantioselective domino approach to multi‐substituted piperidines based on PTC.