2. Academic Validation
  3. Enantiodivergent Rh-Catalyzed Reductive Hydroformylation of Alkenyl Boronic Esters

Enantiodivergent Rh-Catalyzed Reductive Hydroformylation of Alkenyl Boronic Esters

  • Angew Chem Int Ed Engl. 2026 Jan 9;65(2):e20602. doi: 10.1002/anie.202520602.
Yiteng Yu # 1,  Yuchen Zhang # 2,  Xiao-Song Xue 2 3,  Xinquan Hu 1,  Wenjun Tang 4 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Green-Chemical Synthesis and Conversion Technology, the College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, China.
  • 2 State Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China.
  • 3 School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
  • 4 State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling Ling Road, Shanghai, 200032, China.
  • # Contributed equally.
PMID: 41217070 DOI: 10.1002/anie.202520602
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.

Keywords

Alkenyl boronic esters; Camouflage; Enantiodivergent; Enantioselectivity; Hydroformylation.

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