Categories: Synthesis of N-Heterocycles > Synthesis of Cyclic Amines >
Synthesis of piperazines
Recent Literature
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 (pyridyl)phosphine-ligated ruthenium(II) catalyzes a diol-diamine coupling
to provide piperazines and diazepanes. The conditions tolerate different amines
and alcohols that are relevant to key medicinal platforms.
A. Nalikezhathu, A. Tam, V. Cherepakhin, V. K. Do. T. J. Williams, Org. Lett., 2023, 25,
1754-1759.
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.
Related
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.