Synthesis of novel enantiopure 4-hydroxypipecolic acid derivatives with a bicyclic beta-lactam structure from a common 3-azido-4-oxoazetidine-2-carbaldehyde precursor.
Two different stereocontrolled accesses to new 4-hydroxypipecolic acid analogues with a bicyclic beta-lactam structure have been developed by using intramolecular reductive amination or allenic hydroamination reactions in 2-azetidinone-tethered azides. The access to the cyclization precursors was achieved from 3-azido-4-oxoazetidine-2-carbaldehyde via metal-mediated carbonyl-allenylation in aqueous environment or by organocatalytic direct aldol reaction. The tin hydride-promoted cyclization of the 2-azetidinone-tethered azidoallene is totally regioselective for the central allenic carbon providing a fused piperidine.
Alcaide
Benito
B
Departamento de Química OrgAnica I, Facultad de Química, Universidad Complutense de Madrid, 28040-Madrid, Spain. alcaideb@quim.ucm.es
Almendros
Pedro
P
Luna
Amparo
A
Martínez del Campo
Teresa
T
D001384:Azetidines / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D047090:beta-Lactams / Q000737:chemistry*
C528469:3-azido-4-oxoazetidine-2-carbaldehyde; D001384:Azetidines; D001643:Bridged Bicyclo Compounds; D010875:Pipecolic Acids; D047090:beta-Lactams; C094924:4-hydroxypipecolic acid