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Synthesis of 1,2,3,4-tetrahydropyridines

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In situ transformation of a metathesis active Ru-carbene into an isomerization active Ru-hydride catalyst by addition of hydroxide as a chemical trigger enables the conversion of N-Allyl-N-homoallylamines in one step into cyclic enamides via a tandem catalytic ring-closing metathesis-isomerization sequence.
B. Schmidt, S. Hauke, N. Mühlenberg, Synthesis, 2014, 46, 1648-1658.


Ring-closing metathesis reactions of olefin-containing enamides using ruthenium-based catalysts provides protected five- and six-membered cyclic enamides.
S. S. Kinderman, J. H. van Maarseveen, H. E. Schoemaker, H. Hiemstra, F. P. J. T. Rutjes, Org. Lett., 2001, 3, 2077-2079.


A dehydrogenation of amides to enamides employs the combination of LiHMDS and triflic anhydride, which serves as both the electrophilic activator and the oxidant. The reaction offers simple setup and broad substrate scope. The synthetic utility of the formed enamides was demonstrated in a range of transformations.
P. Spiess, M. Berger, D. Kaiser, N. Maulide, J. Am. Chem. Soc., 2021, 143, 10524-10529.


Suzuki coupling reactions of alkenylboronates and arylboronic acids with six- and seven-membered lactam-derived N-alkoxycarbonyl vinyl triflates provide the corresponding 6- or 7-substituted N-alkoxycarbonyl-3,4-dihydro-2H-pyridines and N-alkoxycarbonyl-2,3,4,5-tetrahydroazepines in high yields under very mild conditions.
E. G. Occhiato, A. Trabocchi, A. Guarna, J. Org. Chem., 2001, 66, 2459-2465.


A Rh-catalyzed asymmetric reductive Heck reaction of aryl, heteroaryl, or vinyl boronic acids and phenyl pyridine-1(2H)-carboxylate provides 3-substituted tetrahydropyridines in high yield and excellent enantioselectivity with a wide functional group tolerance. A subsequent reduction provides access to a wide variety of enantioenriched 3-piperidines.
S. Mishra, S. Karabiyikoglu, S. P. Fletcher, J. Am. Chem. Soc., 2023, 145, 14221-14226.


A palladium-catalyzed cyclization-Heck reaction of allenamides enables an efficient one-pot construction of functionalized 3-methylene-5-aryl-1,2,3,4-tetrahydropyridines. These compounds feature a nonconjugated diene, including one endo-enamine and one exocyclic double bond, which could be used for further transformation.
F. Yan, H. Liang, J. Song, J. Cui, Q. Liu, S. Liu, P. Wang, Y. Dong, H. Liu, Org. Lett., 2017, 19, 86-89.


Cascade reactions of saturated cyclic amines with 2-oxo-2-arylacetic acids enable a highly regioselective and versatile synthesis of acylated N-heterocycles. In this cascade process, the copper catalyst is believed to play a crucial role not only in dehydrogenation but also in the decarboxylation and cross coupling reaction.
X. Shi, X. Chen, M. Wang, X. Zhang, X. Fan, J. Org. Chem., 2018, 83, 6524-6533.


An efficient chiral Lewis acid-catalyzed inverse-electron-demand Diels-Alder reaction of N-sulfonyl 1-aza-1,3-dienes is based on the combination of Ni(II)-DBFOX complex as catalyst and the use of a metal-coordinating (8-quinolyl)sulfonyl moiety. The reaction provides highly functionalized piperidine derivatives in good yields with excellent endo-selectivity, and good enantioselectivities.
J. Esquivias, R. G. Arrays, J. C. Carretero, J. Am. Chem. Soc., 2007, 129, 1480-1481.