Synthesis of 3-Hydroxymethyl Isoindolinones via Cobalt-Catalyzed C(sp2)-H Carbonylation of Phenylglycinol Derivatives.

Abstract

An efficient method for the synthesis of 3-hydroxymethyl isoindolinones via cobalt-catalyzed C(sp2)-H carbonylation of phenylglycinol derivatives using picolinamide as a traceless directing group is demonstrated. The reaction proceeds in the presence of a commercially available cobalt(II) tetramethylheptanedionate catalyst and employs DIAD as a "CO" surrogate. This synthetic route offers a broad substrate scope, excellent regioselectivity, and full preservation of the original stereochemistry. Besides, the developed method provides a pathway for accessing valuable enantiopure 3-substituted isoindolinone derivatives.