Synthesis of piperazines
A practical method allows the synthesis of alkyl-, alcohol-, amine-, and ester-extended tosylpiperazines under mild conditions with good yields. This protocol exhibits potential applicability in the synthesis of pharmaceuticals and natural products because of the operational simplicity and the conveniently available reactants.
J. Huang, W. Xu, H. Xie, S. Li, J. Org. Chem., 2012, 77, 7506-7511.
A facile Pd-catalyzed methodology provides an efficient synthetic route to biologically relevant arylpiperazines under aerobic conditions. Electron donating and sterically hindered aryl chlorides were aminated to afford very good yields of the desired products. Using 2.5 eq. piperazine as solvent enables an ecofriendly, cost-effective synthesis of these privileged structures.
S. W. Reilly, R. H. Mach, Org. Lett., 2016, 18, 5272-5275.
A visible-light-promoted decarboxylative annulation protocol between a glycine-based diamine and various aldehydes provides 2-aryl, 2-heteroaryl, as well as 2-alkyl piperazines under mild conditions. The iridium-based complex [Ir(ppy)2(dtbpy)]PF6 and carbazolyl dicyanobenzene 4CzIPN efficiently catalyze this transformation in batch or in continuous mode.
R. Gueret, L. Pelinski, T. Bousquet, M. Sauthier, V. Ferey, A. Bigot, Org. Lett., 2020, 22, 5157-5162.
A highly diastereoselective intramolecular hydroamination is the key step in a modular synthesis of 2,6-disubstituted piperazines. The requisite hydroamination substrates were prepared in excellent yields by nucleophilic displacement of cyclic sulfamidates derived from amino acids. Various alkyl and aryl substituents at the 2-position were tolerated.
B. M. Cochran, F. E. Michael, Org. Lett., 2008, 10, 329-332.
Use of a base-free Pd(DMSO)2(TFA)2 catalyst enables the synthesis of six-membered nitrogen heterocycles via a Wacker-type aerobic oxidative cyclization of alkenes. Various heterocycles, including morpholines, piperidines, piperazines and piperazinones, are accessible by this method.
Z. Lu, S. S. Stahl, Org. Lett., 2012, 14, 1234-1237.
A palladium-catalyzed cyclization reaction for the modular synthesis of highly substituted piperazines and related bis-nitrogen heterocycles couples two of the carbons of a propargyl unit with various diamine components to provide products in very good yields with high regio- and stereochemical control.
T. D. Montgomery, V. H. Rawal, Org. Lett., 2016, 18, 740-743.
Ring-opening of cyclic sulfamidates with propargylic sulfonamides yielded substrates for a gold-catalyzed cyclization to yield tetrahydropyrazines. Subsequent reduction or multicomponent reactions of the tetrahydropyrazines gave various piperazine scaffolds, that have a certain value in the synthesis of novel screening compounds with lead-like molecular properties.
T. James, I. Simpson, J. Grant, V. Sridharan, A. Nelson, Org. Lett., 2013, 15, 6094-6097.