Aminomethylation of enals through carbene and acid cooperative catalysis: concise access to β(2)-amino acids.
A convergent, organocatalytic asymmetric aminomethylation of α,β-unsaturated aldehydes by N-heterocyclic carbene (NHC) and (in situ generated) Brønsted acid cooperative catalysis is disclosed. The catalytically generated conjugated acid from the base plays dual roles in promoting the formation of azolium enolate intermediate, formaldehyde-derived iminium ion (as an electrophilic reactant), and methanol (as a nucleophilic reactant). This redox-neutral strategy is suitable for the scalable synthesis of enantiomerically enriched β(2) -amino acids bearing various substituents.
Division of Chemistry & Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, Singapore 637371 (Singapore).
Jianfeng
J
Xu
Xingkuan
X
Chen
Ming
M
Wang
Pengcheng
P
Zheng
Bao-An
BA
Song
Yonggui Robin
YR
Chi
D000143:Acids / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D006571:Heterocyclic Compounds / Q000737:chemistry; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D008745:Methylation; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D000143:Acids; D000447:Aldehydes; D000596:Amino Acids; D006571:Heterocyclic Compounds; C030011:carbene; D008697:Methane
Brønsted acid; N-heterocyclic carbenes; amino acids; asymmetric synthesis; organocatalysis