Development of Bifunctional Aza-Bis(oxazoline) Copper Catalysts for Enantioselective Henry Reaction

• Published in: Journal of organic chemistry Vol. 75; no. 19; pp. 6424 - 6435
• Main Authors: Lang, Kai, Park, Jongwoo, Hong, Sukwon
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.10.2010; Amer Chemical Soc
• Subjects: Alcohols - chemical synthesis; Alcohols - chemistry; Aldehydes - chemistry; Aza Compounds - chemistry; Catalysis; Catalysts: preparations and properties; Chemistry; Chemistry, Organic; Copper - chemistry; Exact sciences and technology; General and physical chemistry; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Ligands; Molecular Structure; Noncondensed benzenic compounds; Organic chemistry; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Oxazoles - chemistry; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; HYDROLYTIC KINETIC RESOLUTION; MANNICH-TYPE REACTION; ALPHA-HYDROXY ESTERS; SALEN-CHROMIUM COMPLEXES; DINUCLEAR ZINC CATALYST; ALDOL REACTION; RING-OPENING REACTIONS; COOPERATIVE ASYMMETRIC CATALYSIS; OXAZOLINE-CONTAINING LIGANDS; NITROALDOL REACTION; Lewis acid; Enantioselectivity; Nitrogen heterocycle; Ligand; Bifunctional compound; Oxazoline derivatives; Transition metal; Transition metal Complexes; Copper complex; Reaction rate; Aldol condensation; Copper ion; Functionalization; Asymmetric synthesis; Benzylic compound; Tertiary amine; Enantiomeric excess; Piperazine derivatives; Chemical synthesis; Catalyst activity; Oxazole derivatives; Catalyst; Oxygen nitrogen heterocycle; Henry reaction
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo1009867

Base-functionalized aza-bis(oxazoline) ligands were prepared to explore the concept of dual activation through the Lewis acid and a tethered tertiary amine base. The catalytic activity of the Cu complex was evaluated for the asymmetric Henry reaction. Compared with a corresponding unfunctionalized copper complex with external 1-benzyl-4-ethylpiperazine base, the ethylpiperazine-functionalized aza-bis(oxazoline) copper catalyst resulted in rate acceleration (2.5 times) as well as improved enantioselectivity (72% ee vs 92% ee).