Sequential catalytic asymmetric Heck-iminium ion cyclization: enantioselective total synthesis of the Strychnos alkaloid minfiensine.
A catalytic asymmetric method for the chemical synthesis of alkaloids containing the 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9H-carbazole (1) moiety is reported and verified by the enantioselective total synthesis of (+)-minfiensine (4). The central step in this total synthesis is the sequential catalytic asymmetric Heck-N-acyliminium ion cyclization of dienyl carbamate triflate 10, prepared in six steps from 1,2-cyclohexanedione, to give enantiopure 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazole (12) in 75% yield. Iminoethano-9H-carbazole 12 is transformed in six steps to dienyl iodide 17, which undergoes diastereoselective intramolecular Heck cyclization to form pentacyclic intermediate 18. In eight additional steps, this latter intermediate is transformed to (+)-minfiensine (4).
Dounay
Amy B
AB
Department of Chemistry, University of California, 516 Rowland Hall, Irvine, California 92697-2025, USA.
Overman
Larry E
LE
Wrobleski
Aaron D
AD
D000470:Alkaloids / Q000138:chemical synthesis*; D002227:Carbazoles / Q000138:chemical synthesis*; D003500:Cyclization; D007097:Imines / Q000737:chemistry; D013237:Stereoisomerism; D031451:Strychnos / Q000737:chemistry
D000470:Alkaloids; D002227:Carbazoles; D007097:Imines; C504098:minfiensine