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Updated: Jul 28, 2026

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Synthesis of naturally occurring pyridine alkaloids via palladium-catalyzed coupling/migration chemistry
Yao Wang1, Xiaoyang Dong, Richard C Larock
1Department of Chemistry, Iowa State University, Ames, IA 50011, USA.
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.
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