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Synthesis of Naturally Occurring Pyridine Alkaloids via Palladium-Catalyzed Coupling/Migration Chemistry
journal contribution
posted on 2003-03-20, 00:00 authored by Yao Wang, Xiaoyang Dong, Richard C. LarockThe 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)
π-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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carbopalladationiodopyridineterminalSynthesimethylbenzylic aminesallylpalladiumyieldbondOccurring Pyridine Alkaloidsdisplacementheterocyclic iodideSubsequent hydrogenationpalladium migration processPd catalystnovel routexestamine Doxidativetosylamideregenerationdienenitrogen nucleophileintermediatesynthesisdeprotectionpyridine alkaloid ikimineniphatesine Caldehydepyridine alkaloids theonelladins C