Asymmetric Counter-Anion-Directed Aminomethylation: Synthesis of Chiral β-Amino Acids via Trapping of an Enol Intermediate

Zhenghui Kang; Yongheng Wang; Dan Zhang; Ruibo Wu; Xinfang Xu; Wenhao Hu

doi:10.1021/jacs.8b12832

Asymmetric Counter-Anion-Directed Aminomethylation: Synthesis of Chiral β-Amino Acids via Trapping of an Enol Intermediate

J Am Chem Soc. 2019 Jan 30;141(4):1473-1478. doi: 10.1021/jacs.8b12832. Epub 2019 Jan 14.

Authors

Zhenghui Kang^{1

2}, Yongheng Wang¹, Dan Zhang¹, Ruibo Wu¹, Xinfang Xu¹, Wenhao Hu^{1

2}

Affiliations

¹ School of Pharmaceutical Sciences , Sun Yat-sen University , Guangzhou 510006 , China.
² Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering , East China Normal University , Shanghai 200062 , China.

PMID: 30624920
DOI: 10.1021/jacs.8b12832

Abstract

A novel enantioselective aminomethylation reaction of diazo compound, alcohol and α-aminomethyl ether enabled by asymmetric counteranion-directed catalysis is disclosed that offers an efficient and convenient access to furnish optically active α-hydroxyl-β-amino acids in high yield with high to excellent enantioselectivities. Control experiments and DFT calculations indicate that the transformation proceeds through trapping the in situ generated enol intermediate with methylene iminium ion, and the asymmetric induction was enabled by chiral pentacarboxycyclopentadiene anion via H-bonding and electrostatic interaction.

Publication types

Research Support, Non-U.S. Gov't