Yamada M,
*,
Azuma K,
Yamano M.
Takeda Pharmaceutical Company Limited, Osaka, Japan
Highly Enantioselective Direct Asymmetric Reductive Amination of 2‑Acetyl-6-Substituted Pyridines.
Org. Lett. 2021;
23: 3364-3367
DOI:
10.1021/acs.orglett.1c00848
Key words
ruthenium catalysis - reductive amination - asymmetric synthesis
Significance
The authors report a ruthenium-catalyzed reductive amination of ketones. Ru-(OAc)2((S)-binap) is used as catalyst and ammonium trifluoroacetate as the nitrogen source; hydrogen pressures of 0.8 MPa are needed. The procedure allows the formation of chiral amines in high enantiomeric excess and quantitative conversions. Sensitive functional groups such as esters and amides are tolerated.
Comment
Reductive aminations are widespread reactions in the pharmaceutical industry. This direct asymmetric reductive amination allows for the generation of chiral secondary amines from ketones, which has been challenging before. Diarylketones, fused ring ketones, and 2-acetyl-6-pyridone showed no reaction under these conditions
