Enantiodivergent Rh‐Catalyzed Reductive Hydroformylation of Alkenyl Boronic Esters
Abstract
Abstract 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.
Article Details
Authors (5)
Yiteng Yu
State Key Laboratory of Green‐Chemical Synthesis and Conversion Technology the College of Chemical Engineering Zhejiang University of Technology Hangzhou Zhejiang 310032 China
YuChen Zhang
Xiao‐Song Xue
State Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials Shanghai Institute of Organic Chemistry Chinese Academy of Sciences Shanghai 200032 China
Xinquan Hu
State Key Laboratory of Green‐Chemical Synthesis and Conversion Technology the College of Chemical Engineering Zhejiang University of Technology Hangzhou Zhejiang 310032 China
Wenjun Tang
State Key Laboratory of Bio-Organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry