Cascade CuH-catalysed conversion of alkynes into enantioenriched 1,1-disubstituted products

Additions to alkenes and alkynes are useful routes for generating highly functionalized products. Here the authors report the 1,1-difunctionalization of alkynes through a CuH-catalysed asymmetric hydroboration/hydroamination cascade. Enantioenriched alpha-aminoboronic acids play a unique role in medicinal chemistry and have emerged as privileged pharmacophores in proteasome inhibitors. Additionally, they represent synthetically useful chiral building blocks in organic synthesis. Recently, CuH-catalysed asymmetric alkene hydrofunctionalization has become a powerful tool to construct stereogenic carbon centres. By contrast, applying CuH cascade catalysis to achieve the reductive 1,1-difunctionalization of alkynes remains an important, but largely unaddressed, synthetic challenge. Herein, we report an efficient strategy to synthesize alpha-aminoboron compounds by a CuH-catalysed hydroboration/hydroamination cascade of readily available alkynes. Notably, this transformation selectively delivers the desired 1,1-heterodifunctionalized product rather than the alternative homodifunctionalized, 1,2-heterodifunctionalized or reductively monofunctionalized by-products, thereby offering rapid access to these privileged scaffolds with high chemo-, regio- and enantioselectivity.