title: Concise enantioselective total syntheses of (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine and (+)-norchelidonine by a Pd II-catalyzed ring-opening strategy.
abstract: New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine, and (+)-norchelidonine are described. Our rapid and convergent route to this class of natural products involved the development and application of a Pd II-catalyzed asymmetric ring-opening reaction of a meso-azabicyclic alkene with an aryl boronic acid as the key step. By screening a variety of functionalized ortho-substituted aryl boronic acids, chiral ligands and reaction conditions we were able to prepare the requisite cis-1-amino-2-aryldihydronaphthalenes in high yield and in up to 90 % ee. Early attempts to complete the synthesis of (+)-homochelidonine using an N-Boc azabicyclic alkene are described in full. The successful route required a protecting group alteration followed by B ring formation and then stereoselective installation of the C-11 syn-hydroxy group by regioselective epoxide ring-opening using a hydride source. Ring-opening of the same epoxide intermediate with water ultimately led to the synthesis of (+)-chelamidine. The same strategy was then used to synthesize the other structurally similar B/C hexahydrobenzo[c]phenanthridine alkaloids, (+)-chelidonine, (+)-chelamidine, and (+)-norchelidonine.
authors.affiliation: Department of Chemistry, Davenport Chemical Laboratories, University of Toronto, 80 St. George St., Toronto, ON M5S 3H6, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Fleming
authors.forename: Helen A
authors.initials: HA
authors.lastname: McManus
authors.forename: Alena
authors.initials: A
authors.lastname: Rudolph
authors.forename: Walter H
authors.initials: WH
authors.lastname: Chan
authors.forename: Jérémy
authors.initials: J
authors.lastname: Ruiz
authors.forename: Chris
authors.initials: C
authors.lastname: Dockendorff
authors.forename: Mark
authors.initials: M
authors.lastname: Lautens
mesh_terms: D053119:Benzophenanthridines / Q000138:chemical synthesis* / Q000737:chemistry; D001600:Berberine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D001897:Boronic Acids / Q000737:chemistry; D002384:Catalysis; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D053119:Benzophenanthridines; D001600:Berberine Alkaloids; D001897:Boronic Acids; D009942:Organometallic Compounds; C528543:chelamine; D010165:Palladium; C062047:chelidonine; C517745:homochelidonine