Enantioselective Synthesis of Secondary Homoallyl Borons by Copper-Catalyzed 1,1-Borylallylation of Terminal Alkynes

The development of a single catalyst system that enables cascade reaction processes involving multiple components to occur in a highly chemo-, regio-, and enantioselective manner presents a significant challenge in catalysis. Here, we introduce a direct catalytic asymmetric synthesis of enantioenriched secondary homoallyl borons by assembling four readily available components─terminal alkynes, boron reagents (HBdan), silyl hydrides (PMHS), and allyl electrophiles─in a cascade hydroboration and hydroallylation sequence. This complex assembly line is delicately controlled by a single copper catalyst, effectively overcoming multiple side reactions. The reaction features simple starting materials, mild conditions, structurally diverse products, and high regio- and enantioselectivities (up to >20:1 r.r. and 94% ee). The utility of the resulting products is showcased through their versatile transformations and further demonstrated in the formal total syntheses of natural products such as (−)-bruguierol A, (−)-enterolactone, and (−)-antofine. Mechanistic studies were conducted to illuminate the operative pathway, the key intermediates, and the crucial roles of the hydride source PMHS.