Sweeney, Joseph Bernard and Adams, Kirsty and Doulcet, Julien and Thapa, Bimod and Tran, Fanny and Crook, Robert (2018) Optimizing the Mizoroki–Heck reaction of cyclic allyl amines : Gram-scale synthesis of preclamol without protecting groups. Journal of Catalysis, 360. pp. 97-101. ISSN 0021-9517
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Abstract
Though a widely used metal-catalyzed cross-coupling process, the Mizoroki–Heck (MH) reaction can be a capricious transformation. This is particularly true for oxidation-prone alkene substrates containing ligating heteroatoms, as in the case of N-alkyl tetrahydropyridines, whose MH reactions have been underexplored due to the many side reactions that hamper the process. Since the products of tetrahydropyridine Heck reactions are direct precursors to potent pharmacophores, and therefore of commercial value, this is a significant drawback. We report here the results of our study designed to deliver an optimized, scalable MH procedure for N-alkyltetrahydropyridines and its exemplification in a gram-scale synthesis of the drug substance preclamol.