Ligand-Modulated Cobalt-Catalyzed Alkene Carbocarbonylation Unlocks Aliphatic Ketone Synthesis.

Unsymmetric aliphatic ketones are one of the most versatile functional groups and are commonly found in a plethora of organic molecules and bioactive compounds. Yet, a concise construction of aliphatic ketones via a direct carbonylation strategy still remains challenging, particularly when employing alkenes as versatile feedstocks. By the use of a newly developed bispyrazolylpyridine-type NNN-pincer ligand, we herein report a divergent synthesis of unsymmetric aliphatic ketones through cobalt-catalyzed four-component carbocarbonylation of both activated and unactivated alkenes under 1 atm of CO gas. This methodology encompasses a wide range of alkenes, alkylzinc reagents, and alkyl halides. Of particular interest is the use of highly functionalized CCl4, CF2Br2, and their derivatives as the electrophiles, thus affording modular access to structurally diverse aliphatic ketones, which might find potential applications in synthetic and medicinal chemistry. Moreover, this protocol is also distinguished by its simple operation, excellent functional group compatibility, and high regio- and chemoselectivity.