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.