Diastereodivergent Hydroamidation of Methylenecyclohexanes With Differentiated Active Catalytic Species

The construction of three‐dimensional (3D) organic molecular structures is pivotal in modern organic chemistry. For three dimensionally structured disubstituted cyclohexanes, which exist as two possible configurations ( cis ‐ and trans ‐), substituent orientation dictates thermodynamic stability, physicochemical properties, and biological activities, but precise stereocontrol of cycloalkane substituents is challenging. Herein, we report the diastereodivergent hydroamidation of methylenecyclohexanes: a nickel catalytic system efficiently synthesizes 1,4‐ cis / trans and 1,3‐ cis / trans isomers, while a cobalt system realizes 1,2‐ cis / trans stereodivergence. The core achievement lies in a strategy utilizing differentiated active catalytic species, which enables the precise regulation of the spatial structure and electronic properties of metal‐hydride or metal‐functional group intermediates. This work broadens the chemical space for multi‐substituted cyclohexane synthesis, provides a powerful tool for the preparation of cycloalkyl‐containing drug molecules, and offers an important case for research on substituted cyclohexane stereochemistry.