Cyclization Reaction by MHAT/RPC Mechanism

This review focuses on the recent advancements in the Metal-Hydride Hydrogen Atom Transfer (MHAT) mechanism for alkene transformation, particularly emphasizing the novel applications and methodologies developed in our research over the past decade. Our work has significantly expanded the scope of MHAT by introducing the Radical-Polar Crossover (RPC) concept, thereby enabling a wide range of selective functionalizations and complex molecule constructions that were previously challenging. We have successfully applied MHAT/RPC mechanisms to construct oxygen-containing heterocycles, such as ethers and lactones, integral to numerous bioactive natural products and pharmaceuticals. This has included the development of methods for the efficient synthesis of five- and six-membered rings, as well as challenging medium-sized rings, highlighting the method’s versatility and effectiveness. Furthermore, our research has pioneered the synthesis of nitrogen-containing heterocycles through MHAT, opening new avenues for the creation of cyclic guanidines and azetidines, compounds with significant biological activity. The introduction of asymmetry into the MHAT mechanism has also been a cornerstone of our work, leading to the development of enantioselective transformations that provide access to chiral molecules. Through a combination of experimental and computational studies, we have elucidated the underlying mechanistic pathways of MHAT, offering insights into the reaction dynamics and factors influencing selectivity and efficiency. Our contributions not only demonstrate the broad applicability of the MHAT mechanism in organic synthesis but also pave the way for future innovations in the field, with the potential for developing new strategies for complex molecule synthesis.