title: Base-catalyzed intramolecular hydroamination of cyclohexa-2,5-dienes: insights into the mechanism through DFT calculations and application to the total synthesis of epi-elwesine.
abstract: The base-catalyzed intramolecular hydroamination of 1-ethylaminocyclohexa-2,5-dienes is described. The transformation proceeds through isomerization of the cyclohexa-1,4-dienyl fragment into the corresponding conjugated 1,3-diene prior to the hydroamination step. Attaching a chiral glycinol ether auxiliary on the amino group allows the protonation to occur with complete diastereocontrol. The resulting lithium amide then adds onto the 1,3-dienyl moiety, affording the desired fused pyrrolidine ring along with the corresponding lithium allylic anion. Protonation of the latter then proceeds with high regiocontrol to favor the resulting allylic amines. In contrast, when the reaction was performed on primary amines, fused pyrrolidines bearing a homoallylic amino group were obtained. The stereochemical course of the process and determination of the reaction pathways were established based on calculations performed at the DFT level. Finally, application of the methodology to the enantioselective synthesis of (+)-epi-elwesine, a crinane alkaloid, is described.
authors.affiliation: ISM, UMR 5255, University of Bordeaux and CNRS, 351, Cours de la liberation, 33400 Talence Cedex (France).
authors.forename: Géraldine
authors.initials: G
authors.lastname: Rousseau
authors.forename: Raphaël
authors.initials: R
authors.lastname: Lebeuf
authors.forename: Kurt
authors.initials: K
authors.lastname: Schenk
authors.forename: Frédéric
authors.initials: F
authors.lastname: Castet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Robert
authors.forename: Yannick
authors.initials: Y
authors.lastname: Landais
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D047151:Amaryllidaceae Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000586:Amination; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D053138:Cyclohexenes / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D047151:Amaryllidaceae Alkaloids; D000588:Amines; D053138:Cyclohexenes; D011759:Pyrrolidines
keywords: alkaloids; hydroamination; isomerization; reaction mechanisms; rearrangements