Rights statement: This is the author’s version of a work that was accepted for publication in Journal of Catalysis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Catalysis, 360, 2018 DOI: 10.1016/j.jcat.2018.01.007
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Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Optimizing the Mizoroki–Heck reaction of cyclic allyl amines
T2 - Gram-scale synthesis of preclamol without protecting groups
AU - Sweeney, Joseph Bernard
AU - Adams, Kirsty
AU - Doulcet, Julien
AU - Thapa, Bimod
AU - Tran, Fanny
AU - Crook, Robert
N1 - This is the author’s version of a work that was accepted for publication in Journal of Catalysis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Catalysis, 360, 2018 DOI: 10.1016/j.jcat.2018.01.007
PY - 2018/4
Y1 - 2018/4
N2 - 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.
AB - 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.
KW - Catalysis
KW - Tetrahydropyridines
KW - Mizoroki–Heck reaction
KW - Aryl piperidines
KW - CNS drugs
U2 - 10.1016/j.jcat.2018.01.007
DO - 10.1016/j.jcat.2018.01.007
M3 - Journal article
VL - 360
SP - 97
EP - 101
JO - Journal of Catalysis
JF - Journal of Catalysis
SN - 0021-9517
ER -