[4 + 2] Cycloadditions of N-Alkenyl Iminium Ions: Structurally Complex Heterocycles from a Three-Component Diels-Alder Reaction Sequence

摘要

Nitrogen-containing heterocycles are ubiquitous substructures in a myriad of biologically active natural products and small-molecule Pharmaceuticals. Accordingly, a wide range of target-directed and diversity-oriented synthesis activities are devoted to heterocycle synthesis. As a strategy for expanding existing hetero-Diels-Alder-based approaches to heterocycle synthesis, we were attracted to cationic 2-azadienes 1 as conduits to three-component [4 + 2] cycloaddition reactions accessing structurally and stereochemically diverse piperidine derivatives (Figure 1). The putative N-alkenyl iminium ion-alkene [4 + 2] cycloadditions would generate tetrahydropyridinium ion cycloadducts 2, allowing further functionalization through nucleophilic addition to the transposed iminium ion 2. Herein, we describe N-alkenyl iminium ions 1 as enabling tools for three-component [4 + 2] cycloaddition-iminium ion addition reactions that afford an efficient and versatile synthesis of highly substituted piperidines.