Organocatalytic approach to vinylic nucleophilic substitution at electrophilic alkenes

Abstract

Nucleophilic catalysis is a powerful and well-developed tool for activating and manipulating carbon-centered electrophiles. However, its application to substitution at sp²-carbon atoms has been explored only for acylation reactions and, to a limited extent, nucleophilic aromatic substitution. limited to a handful of molecular moieties. Herein, we report that dimethylaminopyridine efficiently promotes the nucleophilic substitution reactions of β-chlorinated Michael acceptors with various O-, N-, S- and C-nucleophiles in terms of electronic and steric properties. The reactions proceed via the formation of vinylpyridinium electrophilic species, which can be either generated in situ under catalytic conditions or, more beneficially, isolated and used further in a separate synthetic step. The executed reactions include preparation of relevant pharmaceutical precursors and cascade processes. Furthermore, quantum chemical calculation methods quantified a rate increase of the key substitution step of a catalytic reaction by approximately 10⁶ times compared to a non-catalyzed reaction and established an impact of intermolecular noncovalent interactions on the reaction course.