Enantioselective synthesis of angularly substituted 1-azabicyclic ring systems: dynamic kinetic resolution using aza-Cope rearrangements.
A useful enantioselective synthesis of angularly substituted 1-azabicyclic molecules that delivers the bicyclic amine products in good yield and 99% ee is reported. Angularly substituted cis-octahydrocyclopenta[b]pyrroles, cis-octahydroindoles, cis-decahydrocyclohepta[b]pyrroles, and cis-octahydrocyclopenta[b]pyridine are formed in good yields and 99% ee exclusively as the cis stereoisomers. Decahydroquinolines are generated as mixtures of cis and trans stereoisomers in similarly high ee. The starting materials for this cascade transformation are assembled in five steps from cycloalkanones and enantiomerically pure (R)-2-phenyl-3-butenamine. This enantioselective synthesis introduces a new strategy for dynamic kinetic resolution in which a rapid tautomeric equilibration of diastereomeric iminium cations is combined with a diastereoselective sigmatropic rearrangement.
Ito
Tatsuya
T
Department of Chemistry, University of California, Irvine, 1102 Natural Sciences II, Irvine, California 92697-2025, USA.
Overman
Larry E
LE
Wang
Jocelyn
J
D001372:Aza Compounds / Q000737:chemistry*; D053961:Azabicyclo Compounds / Q000138:chemical synthesis*; D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis*; D011725:Pyridines / Q000138:chemical synthesis*; D011758:Pyrroles / Q000138:chemical synthesis*; D013237:Stereoisomerism
D001372:Aza Compounds; D053961:Azabicyclo Compounds; D007211:Indoles; D011725:Pyridines; D011758:Pyrroles