title: Constructing Iboga alkaloids via C-H bond functionalization: examination of the direct and catalytic union of heteroarenes and isoquinuclidine alkenes.
abstract: The iboga alkaloids have attracted considerable attention in both the scientific community and popular media due to their reported ability to reverse or markedly diminish cravings for, and self-administration of, the major drugs of abuse. We have developed three new intramolecular C-H functionalization procedures leading to the core seven-membered ring of the iboga skeleton, a cyclization that proved to be highly challenging. The electrophilic palladium salt Pd(CH3CN)4(BF4)2 was effective for the cyclization of diverse N-(2-arylethyl)isoquinuclidines with yields of 10-35%. A two-step, bromination-reductive Heck reaction protocol was also effective for the synthesis of ibogamine in 42% yield. Finally, a direct Ni(0)-catalyzed C-H functionalization provided the benzofuran analogues of ibogamine (74%) and epi-ibogamine (38%). Although each approach suffers from significant shortcomings, in combination, the methods described provide practical routes to diverse ibogamine analogues.
authors: Department of Chemistry, Columbia University , New York, New York 10027, United States.
authors: Andrew C
authors: AC
authors: Kruegel
authors: Souvik
authors: S
authors: Rakshit
authors: Xiaoguang
authors: X
authors: Li
authors: Dalibor
authors: D
authors: Sames
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D030014:Tabernaemontana / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000475:Alkenes; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D010165:Palladium