title: Enantioselective, protecting group-free synthesis of 1S-ethyl-4-substituted quinolizidines.
abstract: A practical enantioselective protecting group-free four-step route to the key quinolizidinone 6 from phenylglycinol-derived bicyclic lactam 1 is reported. The Grignard addition reaction to 6 takes place stereoselectively to give 1-ethyl-4-substituted quinolizidines 4-epi-207I and 7-9. Following a similar synthetic sequence, 9a-epi-6 is also accessed. However, the addition of Grignard reagents to 9a-epi-6 proceeds in a non-stereoselective manner. In order to gain insight into the different stereochemical outcome in the two series, theoretical calculations on the iminium salts A and B have been performed. The study concludes that the addition of the hydride, which is the step that determines the configuration of the final products, occurs in a stereoelectronic controlled manner. The theoretical study is in agreement with the experimental results.
authors: Laboratory of Organic Chemistry, Faculty of Pharmacy, Institute of Biomedicine (IBUB), University of Barcelona, 08028 Barcelona, Spain. amat@ub.edu
authors: Mercedes
authors: M
authors: Amat
authors: Vladislav
authors: V
authors: Semak
authors: Carmen
authors: C
authors: Escolano
authors: Elies
authors: E
authors: Molins
authors: Joan
authors: J
authors: Bosch
mesh_terms: D001372:Aza Compounds / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D054837:Quinolizidines / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D054837:Quinolizidines