Hiroki Shigehisa

Catalytic transformation of alkenes via the metal-hydride hydrogen atom transfer (MHAT) mechanism has notably advanced synthetic organic chemistry. This review focuses on MHAT/radical-polar crossover (MHAT/RPC) conditions, offering a novel perspective on generating electrophilic intermediates and facilitating various intramolecular reactions. Upon using cobalt hydrides, the MHAT mechanism displayed exceptional chemoselectivity and functional group tolerance, making it invaluable for the construction of complex biologically relevant molecules under mild conditions. Recent developments have enhanced regioselectivity and expanded the scope of MHAT-type reactions, enabling the formation of cyclic molecules via hydroalkoxylation, hydroacyloxylation, and hydroamination. Notably, the addition of an oxidant to traditional MHAT systems enables the synthesis of rare cationic alkylcobalt(IV) complexes, bridging radical mechanisms to ionic reaction systems. This review culminates with examples of natural product syntheses and exploration of asymmetric intramolecular hydroalkoxylation, highlighting the ongoing challenges and opportunities for future research to achieve higher enantioselectivity. This comprehensive study revisits the historical evolution of the MHAT mechanism and provides the groundwork for further innovations in the synthesis of structurally diverse and complex natural products.1 Introduction2 Intramolecular hydroalkoxylation and hydroacyloxylation reactions3 Intramolecular hydroamination reactions4 Intramolecular hydroarylation reactions5 Deprotective cyclization6 Asymmetric intramolecular hydroalkoxylation

This study demonstrates a novel method for synthesizing rare heterocyclic compounds, namely, cyclic isoureas using alkenoic ureas via cobalt-catalyzed metal-catalyzed hydrogen atom transfer/radical polar crossover (MHAT/RPC). This method successfully produces five-membered rings along with the rare six- and seven-membered cyclic isoureas. Density functional theory (DFT) calculations were performed to elucidate the reaction mechanism focusing on cyclization.