title: Total synthesis of the strychnos alkaloid (+)-minfiensine: tandem enantioselective intramolecular Heck-iminium ion cyclization.
abstract: A 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9H-carbazole (4) is a central structural feature of the Strychnos alkaloid minfiensine (1) and akuammiline alkaloids such as vincorine (5) and echitamine (6). A cascade catalytic asymmetric Heck-iminium cyclization was developed that rapidly provides 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazoles in high enantiomeric purity. Two sequences were developed for advancing 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazole 27 to (+)-minfiensine. In our first-generation approach, a reductive Heck cyclization was employed to form the fifth ring of (+)-minfiensine. In a second more concise total synthesis, an intramolecular palladium-catalyzed ketone enolate vinyl iodide coupling was employed to construct the final ring of (+)-minfiensine. This second-generation total synthesis of enantiopure (+)-minfiensine was accomplished in 6.5% overall yield and 15 steps from 1,2-cyclohexanedione and anisidine 13. A distinctive feature of this sequence is the use of palladium-catalyzed reactions to form all carbon-carbon bonds in the transformation of these simple precursors to (+)-minfiensine.
authors.affiliation: Department of Chemistry, University of California, Irvine, 1102 Natural Sciences II, Irvine, California 92697-2025, USA.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Dounay
authors.forename: Philip G
authors.initials: PG
authors.lastname: Humphreys
authors.forename: Larry E
authors.initials: LE
authors.lastname: Overman
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Wrobleski
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D003516:Cycloparaffins / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D031451:Strychnos / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D002227:Carbazoles; D003516:Cycloparaffins; D004852:Epoxy Compounds; D007097:Imines; D007477:Ions; C504098:minfiensine