Categories: Synthesis of N-Heterocycles >
Synthesis of indolizines
Organocopper reagents smoothly react with heterocyclic propargyl mesylates at low temperature to produce N-fused heterocycles. The copper reagent generates allenyl intermediates in situ via SN2'-substitution and copper byproducts also mediate the subsequent cycloisomerization step.
D. Chernyak, S. B. Gadamsetty, V. Gevorgyan, Org. Lett., 2008, 10, 2307-2310.
A samarium-catalyzed C(sp3)-H bond activation enables the synthesis of a broad range of indolizines from 2-alkylazaarenes and propargylic alcohols under mild, solvent-free conditions.
X. Wang, S.-y. Li, Y.-m. Pan, H.-s. Wang, H. Liang, Z.-f. Chen, X.-h. Qin, Org. Lett., 2014, 16, 580-583.
An efficient and one-step synthesis of 3-aminoindolizines or benz[e]indolizines from the reactions of propargyl amines or amides with heteroaryl bromides is realized by a tandem reaction using Pd/Cu catalysts, which catalyze coupling and cycloisomerization reactions in the same vessel.
Y. Liu, Z. Song, B. Yan, Org. Lett., 2007, 9, 409-412.
A gold(III)-catalyzed multicomponent coupling/cycloisomerization reaction of heteroaryl aldehydes, amines, and alkynes under solvent-free conditions or in water provides rapid access to substituted aminoindolizines with high atom economy and high catalytic efficiency.
B. Yan, Y. Liu, Org. Lett., 2007, 9, 4323-4326.
A Fe(acac)3/TBAOH-catalyzed three-component coupling-cycloisomerization reaction of aldehydes, terminal alkynes, and amines provides a diverse range of heterocyclic compounds such as aminoindolizines and quinoline derivatives in good yields.
S. S. Patil, S. V. Patil, V. D. Bobade, Synlett, 2011, 2379-2383.
Facile cycloaromatization of 2-acetylpyrrole derivatives enables a new synthetic route to indolizines with various substituents on the pyridine moiety. The resulting O-triflates permitted introduction of diverse substituents at the C8 position of an indolizine skeleton by Suzuki-Miyaura cross-coupling with (hetero)arylboronic acids.
J. H. Lee, I. Kim, J. Org. Chem., 2013, 78, 1283-1288.
A copper-catalyzed cycloisomerization of 2-pyridyl-substituted propargylic acetates and its derivatives offers an efficient route to C-1 oxygenated indolizines with a wide range of substituents under mild reaction conditions. The presented method could be readily applied to the synthesis of indolizinones through a cyclization/1,2-migration of tertiary propargylic alcohols.
B. Yan, Y. Zhou, H. Zhang, J. Chen, Y. Liu, J. Org. Chem., 2007, 72, 7783-7786.
An efficient two-component palladium-catalyzed arylation/cyclization cascade approach toward various highly functionalized N-fused pyrroloheterocycles in very good yield proceeds via a palladium-catalyzed coupling of aryl halides with propargylic esters or ethers followed by a 5-endo-dig cyclization.
D. Chernyak, C. Skontos, V. Gevorgyan, Org. Lett., 2010, 12, 3242-3245.
An Au-catalyzed synthesis of fused pyrroloheterocycles from diverse propargyl-substituted heterocycles proceeds via alkyne-vinylidene isomerization with concomitant 1,2-shift of hydrogen, silyl, and stannyl groups. This method allows for mild and efficient synthesis of diverse C-2 substituted N-heterocycles.
I. V. Seregin, V. Gevorgyan, J. Am. Chem. Soc., 2006, 128, 12050-12051.
Conditions for the palladium-catalyzed direct arylation of a wide range of heterocycles with aryl bromides employ a stoichiometric ratio of both coupling partners, as well as a substoichiometric quantity of pivalic acid, which results in significantly faster reactions. An evaluation of the influence of the nature of the aryl halide has also been carried out.
B. Liégault, D. Lapointe, L. Caron, A. Vlassova, K. Fagnou, J. Org. Chem., 2009, 74, 1826-1834.