Synthesis of indolizines
A general and efficient Cu-assisted cycloisomerization of alkynyl imines enables an efficient synthesis of pyrroles and various types of fused heteroaromatic compounds.
A. V. Kel'in, A. W. Sromek, V. Gevorgyan, J. Am. Chem. Soc., 2001, 123, 2074-2075.
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.
A Rh-catalyzed asymmetric allylation followed by a Tschitschibabin reaction enables a highly regio- and enantioselective synthesis of 3-allylindolizines in very good yield and high ee with the help of tert-butyl-substituted chiral bisoxazolinephosphine ligand.
K. Li, C. Li, Org. Lett., 2020, 22, 9456-9461.
A copper-catalyzed highly selective oxidative coupling-annulation of 2-alkylazaarenes with terminal alkenes provides a simple, efficient, and atom-economic synthesis of indolizines in good yields.
J.-l. Liu, Y.-L. Liang, H.-s. Wang, Y.-m. Pan, Synlett, 2015, 26, 2024-2028.
An iodine-mediated oxidative cyclization reaction between 2-(pyridin-2-yl)acetate derivatives and different alkynes provides substituted indolizines in a regio- and chemoselective fashion.
L. He, Y. Yang, X. Liu, G. Liang, C. Li, D. Wang, W. Pan, Synthesis, 2020, 52, 459-470.
A novel copper/I2-mediated oxidative cross-coupling/cyclization of 2-(pyridin-2-yl)acetate derivatives and simple olefins provides a straightforward and efficient access to 1,3-di- and 1,2,3-trisubstituted indolizines in good yields.
R.-R. Liu, J. J. Hong, C.-J. Lu, M. Xu, J.-R. Gao, Y.-X. Jia, Org. Lett., 2015, 17, 3050-3053.
Two complementary Au(I)-catalyzed methods provide ester-substituted indolizines from easily accessible 2-propargyloxypyridines and either acetoacetates or dimethyl malonate. These reactions tolerate a wide range of functionality, allowing for diversification at three distinct positions of the product.
C. E. Anderson, H. I. Bos, D. M. Dreher, C. T. Hartgerink, C. J. Scholtens, R. J. Staples, J. Org. Chem., 2022, 87, 10241-10249.
A Pd-catalyzed regioselective annulation of 2-(pyridine-2-yl) acetonitrile derivatives and propargyl carbonates provides a straightforward and efficient access to polysubstituted indolizines. The regioselectivity of the reaction highly depends on the choice of the phosphine ligand.
T. Wu, M. Chen, Y. Yang, J. Org. Chem., 2017, 82, 11304-11309.
A Pd-catalyzed reaction of propargylic pyridines with aroyl chlorides provides indolizine derivatives in very good yields via a 5-endo-dig cyclization initiated by an in situ formed acylpalladium species. This transformation successfully occurred in the presence of an N-nucleophilic moiety and acid chlorides.
An efficient synthesis of diversified indolizine derivatives in good yields from pyridines, methyl ketones and alkenoic acids under solvent-free conditions involves a copper-catalyzed bromination of the methyl ketone, 1,3-dipolar cycloaddition of the pyridinium ylide with the alkenoic acid, followed by oxidative decarboxylation and dehydrogenative aromatization of the primary cycloadduct in oxygen atmosphere.
W. Wang, J. Han, J. Sun, Y. Liu, J. Org. Chem., 2017, 82, 2835-2842.
A catalyst and additive-free annulation of 2-pyridylacetates and ynals provides 3-acylated indolizines in very good yields under molecular oxygen. This approach tolerates a wide range of functional groups.
Z. Chen, P. Liang, X. Ma, H. Luo, G. Xu, T. Liu, X. Wen, J. Zheng, H. Ye, J. Org. Chem., 2019, 84, 1630-1639.
A one-pot method enables the synthesis of multisubstituted indolizines from α-halo carbonyl compounds, pyridines, and electron-deficient alkenes via oxidative dehydrogenation under transition-metal-free conditions using TEMPO as an oxidant. This protocol uses readily available starting materials in a convenient procedure under mild reaction conditions.
F. Shi, Y. Zhang, Z. Lu, X. Zhu, W. Kan, X. Wang, H. Hu, Synthesis, 2016, 48, 413-420.
A metal-free catalytic strategy for the facile synthesis of biologically relevant indolizines and imidazopyridines is promoted by amine and N-heterocyclic carbene (NHC) relay catalysis via Michael addition-[3 + 2] fusion of simple azaarenes and α,β-unsaturated aldehydes.
H. Li, X. Li, Y. Yu, J. Li, Y. Liu, H. Li, W. Wang, Org. Lett., 2017, 19, 2010-2013.
An iron-catalyzed synthesis of functionalized indolizines from pyridines and α-substituted allenoates incorporates an annulation followed by an aerobic oxidation.
T. Jin, Z. Tang, J. Hu, H. Yuan, Y. Chen, C. Li, X. Jia, J. Li, Org. Lett., 2018, 20, 413-416.
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.
B2pin2 mediates a radical cascade cyclization/aromatization reaction of enaminone with pyridine to provide valuable functionalized indolizines under metal-, external oxidant-, and base-free conditions. The reaction is compatible with a broad range of functional groups, such as halogens, π-systems, and heterocycles.
W.-W. Ding, Y. Zhou, S. Song, Z.-Y. Han, Org. Lett., 2022, 24, 7350-7354.
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.