Enantiodivergent Rh‐Catalyzed Reductive Hydroformylation of Alkenyl Boronic Esters

We herein report the first enantioselective Rh-catalyzed reductive hydroformylation of alkenyl boronic esters. By employing either "camouflage" or "direct" reductive AHF strategy, enantiodivergent synthesis of chiral γ-boryl alcohols has been developed for the first time in high yields and excellent enantioselectivities with alkene 1,2-diboronic esters or alkenyl boronic esters as the starting materials using rhodium/Ph-BPE as the catalyst. The method has enjoyed high chemo-selectivity, good functional group compatibility, and broad substrate scope. The chiral γ-boryl alcohol or diol products are versatile building blocks applicable to the synthesis of a series of APIs including (S)-tolterodine, (S)-dapoxetine, and (R)-atomaxetine. DFT calculation has revealed the origin of enantiodivergence of Rh-catalyzed reductive AHF of alkenyl boronic esters with Ph-BPE as the chiral ligand. The transformation is promised to provide great synthetic potential in both academia and industry.