Direct Asymmetric α‐C Addition of Glycinate to Nitroalkenes by Pyridoxal/Nd Dual Catalysis

S Shibo Si (The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science Shanghai Normal University Shanghai 200234 China) Q Qingfang Wang (The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science Shanghai Normal University Shanghai 200234 China) Y Yiming Lv (The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science Shanghai Normal University Shanghai 200234 China) H Huifang Liao (The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science Shanghai Normal University Shanghai 200234 China) W Wen‐Wen Chen (The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science Shanghai Normal University Shanghai 200234 China) S Siqi Liu B Baoguo Zhao (The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis)

Abstract

Abstract Direct enantioselective α‐C Michael addition of NH 2 ‐unprotected glycinate to nitroalkenes is a significant organic transformation, which may provide a highly efficient strategy to make bioactive chiral γ‐nitro‐α‐amino acid esters. However, it is extremely challenging to achieve this reaction due to the interference of the reactive NH 2 group, potential [3 + 2] cycloaddition side reaction and complicated stereoselective control. Carbonyl catalysis is an effective strategy to activate glycinate by forming an imine to facilitate the conjugate addition. With a pyridoxal/Nd dual catalytic system, direct asymmetric α‐C conjugate addition of glycinate to nitroalkenes has been successfully developed for the first time, producing a broad range of chiral γ‐nitro‐α‐amino acid esters in high yields with excellent stereoselectivities (up to 98% yield, >20:1 dr, 98% ee). The products can be easily converted into various biologically significant chiral molecules maintaining the same enantiopurity.

Article Details

Volume / Issue Vol. 64, Issue 34
Published August 18, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (7)

S

Shibo Si

The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science Shanghai Normal University Shanghai 200234 China

Q

Qingfang Wang

The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science Shanghai Normal University Shanghai 200234 China

Y

Yiming Lv

The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science Shanghai Normal University Shanghai 200234 China

H

Huifang Liao

The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science Shanghai Normal University Shanghai 200234 China

W

Wen‐Wen Chen

The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis, and College of Chemistry and Materials Science Shanghai Normal University Shanghai 200234 China

S

Siqi Liu

B

Baoguo Zhao

The Education Ministry Key Lab of Resource Chemistry, Shanghai Frontiers Science Center of Biomimetic Catalysis