Core diversification using 1,2-oxaborines as a versatile molecular platform

In drug discovery processes, changing the core structures of lead compounds to a variety of other ring systems is often needed, which typically requires laborious de novo syntheses of individual analogues. Here we report a conceptually different approach that allows rapid access to diverse core structures from a common intermediate using 1,2-oxaborines as a versatile molecular platform. A soft enolization/6π-electrocyclization strategy has been developed to efficiently synthesize 1,2-oxaborines from readily available enones or enals. Taking advantage of their multifaceted reactivities, 1,2-oxaborines can undergo further C-H functionalization and be transformed into a diverse range of arenes, heteroarenes and non-aromatic heterocycles. Finally, late-stage preparations of a suite of analogues that contain Lipitor substituents but with different aromatic cores are demonstrated using the 1,2-oxaborine-based core diversification strategy.