title: Synthesis of naturally occurring pyridine alkaloids via palladium-catalyzed coupling/migration chemistry.
abstract: The palladium-catalyzed cross-coupling of 3-iodopyridine, long-chain terminal dienes, and benzylic amines or tosylamides provides a novel route to key intermediates for the synthesis of the naturally occurring, biologically active pyridine alkaloids theonelladins C and D, niphatesine C, and xestamine D. This process involves (1) oxidative addition of the heterocyclic iodide to Pd(0), (2) carbopalladation of the least hindered carbon-carbon double bond of the diene, (3) palladium migration, and (4) pi-allylpalladium displacement by the nitrogen nucleophile with simultaneous regeneration of the Pd catalyst. Subsequent hydrogenation and deprotection affords good yields of the natural products. The Pd-catalyzed coupling of 3-iodopyridine and 2-methyl-11-dodecen-1-ol provides a convenient synthesis of a long-chain aldehyde by an analogous palladium migration process, which is easily converted to the pyridine alkaloid ikimine A.
authors.affiliation: Department of Chemistry, Iowa State University, Ames, IA 50011, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Dong
authors.forename: Richard C
authors.initials: RC
authors.lastname: Larock
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis*; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D006847:Hydrocarbons, Iodinated / Q000737:chemistry; D007202:Indicators and Reagents; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis*
chemical_list: D000470:Alkaloids; D006847:Hydrocarbons, Iodinated; D007202:Indicators and Reagents; D011725:Pyridines; D010165:Palladium