Mechanistic Investigation of the Rhodium-Catalyzed Transfer Hydroarylation Reaction Involving Reversible C–C Bond Activation

Carbon–carbon
(C–C) bonds are ubiquitous but are
among the least reactive bonds in organic chemistry. Recently, catalytic
approaches to activate C–C bonds by transition metals have
demonstrated the synthetic potential of directly reorganizing the
skeleton of small molecules. However, these approaches are usually
restricted to strained molecules or rely on directing groups, limiting
their broader impact. We report a detailed mechanistic study of a
rare example of catalytic C–C bond cleavage of unstrained alcohols
that enables reversible ketone transfer hydroarylation under Rh-catalysis.
Combined insight from kinetic analysis, in situ nuclear magnetic resonance
(NMR) monitoring, and density functional theory (DFT) calculations
supports a symmetric catalytic cycle, including a key reversible β-carbon
elimination event. In addition, we provide evidence regarding the
turnover-limiting step, the catalyst resting state, and the role of
the sterically encumbered NHC ligand. The study further led to an
improved catalytic system with the discovery of two air-stable precatalysts
that showed higher activity for the transformation in comparison to
the original conditions.