We report a Rh-catalyzed asymmetric hydroformylation of 1,1-disubstituted alkenyl boronic esters that provides direct access to a previously inaccessible class of dual-functional linchpin synthons bearing both an aldehyde and a boronic ester. These two orthogonal and highly programmable functional groups offer exceptional diversification potential, enabling independent or sequential derivatizations through numerous established reaction platforms. Using a Rh/(S,S)-DTBM-YanPhos system, the transformation proceeds with high chemoselectivity, broad substrate scope, and excellent enantioselectivity, thereby addressing long-standing challenges in the synthesis of chiral alkyl boron reagents. Scale-up studies delivered TON of up to 4050, underscoring the robustness and practical utility of the method. The synthetic value of the resulting bifunctional products is further showcased through concise derivatizations and formal syntheses of (S)-Fluoxetine and (R)-Atomoxetine, highlighting their potential as versatile, densely functionalized building blocks for complex molecule construction.
Zhu et al. (Thu,) studied this question.