Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation.

Hypervalent iodine catalysis has been widely utilized in olefin functionalization reactions. Intermolecularly, the regioselective addition of two distinct nucleophiles across the olefin is a challenging process in hypervalent iodine catalysis. We introduce here a unique strategy using simple lithium salts for hypervalent iodine catalyst activation. The activated hypervalent iodine catalyst allows the intermolecular coupling of soft nucleophiles such as amides onto electronically activated olefins with high regioselectivity.

Olefin Difunctionalization for the Synthesis of Tetrahydroisoquinoline, Morpholine, Piperazine, and Azepane.

This report outlines a versatile strategy for synthesizing a diverse array of N-heterocycles. By the utilization of common olefins, this simple protocol facilitates their coupling with various bifunctional reagents. Furthermore, it can be integrated with C-H amination techniques to directly produce N-heterocycles in a multicomponent cascade coupling process. The unique bond disconnection logic employed in this process underscores its efficiency in achieving rapid simplification through cascade couplings.

Tunable [3+2] and [4+2] annulations for pyrrolidine and piperidine synthesis.

N-heterocycles are privileged pharmaceutical scaffolds in drug discovery and development. We disclose here divergent intermolecular coupling strategies that can access diverse N-heterocycles directly from olefins. The radical-to-polar mechanistic switching is key for the divergent cyclization processes. These distinctive annulations result in the coupling of alkenes with simple bifunctional reagents for divergent N-heterocycle syntheses.