title: Mechanistic studies on the catalytic asymmetric Mannich-type reaction with dihydroisoquinolines and development of oxidative Mannich-type reactions starting from tetrahydroisoquinolines.
abstract: Detailed mechanistic studies on our recently reported asymmetric addition reactions of malonates to dihydroisoquinolines (DHIQs) catalyzed by chiral Pd(II) complexes were carried out. It was found that an N,O-acetal was generated in situ by the reaction of DHIQ with (Boc)2O, and cooperative action of the Pd(II) complex as an acid-base catalyst allowed the formation of a chiral Pd enolate and a reactive iminium ion via alpha-fragmentation. The iminium ion was also accessible via oxidation with DDQ as an oxidant, and a catalytic asymmetric oxidative Mannich-type reaction was achieved with tetrahydroisoquinolines (THIQs) as starting materials. This oxidation protocol was applicable to N-acryloyl-protected THIQs, allowing the efficient synthesis of optically active tetrahydrobenzo[a]quinolizidine derivatives via intramolecular Michael reaction.
authors.affiliation: Synthetic Organic Chemistry Laboratory, RIKEN 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Christian
authors.initials: C
authors.lastname: Dubs
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hamashima
authors.forename: Naoki
authors.initials: N
authors.lastname: Sasamoto
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Seidel
authors.forename: Shoko
authors.initials: S
authors.lastname: Suzuki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hashizume
authors.forename: Mikiko
authors.initials: M
authors.lastname: Sodeoka
mesh_terms: D000588:Amines / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D007546:Isoquinolines / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008352:Mannich Bases / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013696:Temperature
chemical_list: D000588:Amines; D004952:Esters; D007097:Imines; D007546:Isoquinolines; D008024:Ligands; D008352:Mannich Bases; D010165:Palladium