Highly enantioselective carbene insertion into N–H bonds of aliphatic amines

• Published in: Science (American Association for the Advancement of Science) Vol. 366; no. 6468; pp. 990 - 994
• Main Authors: Li, Mao-Lin, Yu, Jin-Han, Li, Yi-Hao, Zhu, Shou-Fei, Zhou, Qi-Lin
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 22.11.2019; The American Association for the Advancement of Science
• Subjects: Aliphatic amines; Amines; Amines - chemistry; Amino acids; Amino Acids - chemistry; Carbon; Catalysis; Catalysts; Chemical bonds; Chemistry Techniques, Synthetic; Coordination compounds; Copper; Copper - chemistry; Copper compounds; Enantiomers; Esters; Forging; Hydrogen Bonding; Insertion; Kinetics; Methane - analogs & derivatives; Methane - chemistry; Molecular Structure; Nitrogen; Selectivity; Stereoisomerism; Thiourea; Thiourea - chemistry; Thioureas; Transition metals
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.aaw9939

Aliphatic amines strongly coordinate, and therefore easily inhibit, the activity of transition-metal catalysts, posing a marked challenge to nitrogen-hydrogen (N–H) insertion reactions. Here, we report highly enantioselective carbene insertion into N–H bonds of aliphatic amines using two catalysts in tandem: an achiral copper complex and chiral amino-thiourea. Coordination by a homoscorpionate ligand protects the copper center that activates the carbene precursor. The chiral amino-thiourea catalyst then promotes enantioselective proton transfer to generate the stereocenter of the insertion product. This reaction couples a wide variety of diazo esters and amines to produce chiral α-alkyl α–amino acid derivatives.