Bioinspired Functionalization of Carbonyl Compounds Enabled by Metal Chelated Bifunctional Ligands.

In Nature, enzymatic reactions proceed through exceptionally ordered transition states giving rise to extraordinary levels of stereoselection. In those reactions, the active site of the enzyme plays crucial roles - through one position, it holds the substrate in the proximity to the reaction epicentre that facilitates both the reactivity and stereoselectivity of the chemical process. Inspired by this natural phenomenon, synthetic chemists have designed bifunctional ligands that not only coordinate to a metal centre but also preassociate with an organic substrate, for example aldehyde and ketone, and exerts stereodirecting influence to accelerate the attack of the incoming reacting partner from a particular enantiotopic face. The chief goal of the current review is to give an overview of the recently developed approaches enabled by privileged bio-inspired bifunctional ligands that not only bind to the metal catalyst but also activates carbonyl substrates via organocatalysis, thereby easing in the new bond forming step. As carbonyl α-functionalizations are dominated by enamine and enolate chemistry, the current review primarily focusses on enamine- and enolate-metal catalysis by bifunctional ligands. Thus, developments based on traditional cooperative catalysis occurring through two directly coupled but independent catalytic cycles of an organocatalyst and a metal catalyst are not covered.