Synthesis of N-Heterocycles

Synthesis of

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Name Reactions

Biginelli Reaction

Hetero-Diels-Alder Reaction

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Recent Literature

A high-yielding, asymmetric synthesis of novel 4-formyl-1-(2- and 3-haloalkyl)azetidin-2-ones was developed as valuable starting materials for the synthesis of different enantiomerically enriched bicyclic azetidin-2-ones, such as piperazine, morpholine, and 1,4-diazepane annulated β-lactam derivatives.
W. Van Brabandt, M. Vanwalleghem, M. D'hooghe, N. De Kimpe, J. Org. Chem., 2006, 71, 7083-7086.

A [2 + 1 + 1] radical tandem cycloaddition of styrenes, arylamines, and tert-butyl hydroperoxide enables a regioselective synthesis of polysubstituted 1,2-oxazetidines. TBHP was employed in this conversion not only as the oxidant but also as the oxygen source.
W. Liu, C. Chen, P. Zhou, H. Tan, Org. Lett., 2017, 19, 5830-5832.

An unprecedented (3+1) cyclization of α-nitrosostyrenes, generated in situ from α-bromooximes, and N-tosyloxycarbamates provides structurally unique 2,3-dihydrodiazete N-oxides in good yields. These highly strained four-membered ring structure products containing two nitrogen atoms can be converted to diverse nitrogen-containing compounds.
L.-W. Shen, Z.-H. Wang, Y. You, J.-Q. Zhao, M.-Q. Zhou, W.-C. Yuan, Org. Lett., 2022, 24, 1094-1099.

Bisphosphine-catalyzed mixed double-Michael reactions between amino-acid-derived pronucleophiles as Michael donors and electron-deficient acetylenes as acceptors afford β-amino carbonyl derivatives of oxazolidines, thiozolidines, and pyrrolidines in excellent yields and with high diastereoselectivities under operationally simple and mild conditions.
V. Sriramurthy, G. A. Barcan, O. Kwon, J. Am. Chem. Soc., 2007, 129, 12928-12929.

Azirinyl-substituted diazodicarbonyl compounds, prepared from diazoacetylazirines, were converted in excellent yields to 2-hydroxy-3-oxo-2,3-dihydro-1H-pyrrole-2-carboxylates under Rh catalysis in the presence of water.
T. O. Zanakhov, E. E. Galenko, M. S. Novikov, A. F. Khlebnikov, J. Org. Chem., 2022, 87, 15598-15607.

A gold-catalyzed 1,3-azaprotio transfer of allenyloximes under photoirradiation enables a construction of five- to seven-membered cyclic nitrones. A photoisomerization of oximes converts the inert stereoisomer to a reactive one. This photodriven and gold-catalyzed ring formation could be further extended to thermodynamically stable aryl ketoximes with an E-configuration.
Z. Qi, S. Wang, J. Org. Chem., 2023, 88, 15395-15403.

In situ generated aza-oxyallyl cation intermediates react with a variety of carbonyl compounds via an efficient (3 + 2) cycloaddition to provide 4-oxazolidinones with good yields and diastereoselectivities.
A. Acharya, K. Montes, C. S. Jeffrey, Org. Lett., 2016, 18, 6083-6085.

A silver oxide catalyzed [3 + 2] annulation of nitrones with isocyanides provides a variety of 2,3,4-trisubstituted 1,2,4-oxadiazolidin-5-one derivatives as single diastereomers in very good yields in the presence of oxygen as the terminal oxidant.
X. Shen, A. Shatskiy, Y. Chen, M. D. Kärkäs, X.-S. Wang, J.-Q. Liu, J. Org. Chem., 2020, 85, 3560-3567.

Photocatalysis enables a straightforward synthesis of 3-oxazolin-5-ones from redox-active esters and secondary nitro compounds. Visible light-induced nondecarboxylative coupling of a redox-active ester, nitro aldol condensation, and subsequent visible light-induced N-oxide deoxygenation were accomplished within 2 h.
S. Ma, H. Cao, R. Gao, Y. Feng, Y. Guo, W. Guan, X. Duan, P. Jiao, Org. Lett., 2023, 25, 2098-2102.

A catalytic asymmetric ring-closing 1,5-C-H amination of sulfamoyl azides provides chiral 1,2,5-thiadiazolidine-1,1-dioxides in up to 98% yield and up to 98% ee if the C-H bond is in a benzylic position. The reaction is catalyzed by a recently introduced simple chiral ruthenium bis(oxazoline) (pybox) complex.
X. Nie, Z. Yan, S. Ivlev, E. Meggers, J. Org. Chem., 2021, 86, 750-761.

An efficient Pd-catalyzed formal [3 + 2] cycloaddition of vinylethylene carbonates with isothiocyanates provides 1,3-oxazolidine-2-thione derivatives. The zwitterionic π-allyl palladium intermediates formed in situ acted as the three-membered synthons.
W. Xiong, S. Zhang, H. Li, Z. Zhang, T. Xu, J. Org. Chem., 2020, 85, 8773-8779.

Silver nitrate catalyzes a reaction of primary amines with methyl α,α-disubstituted α-isocyanoacetates to provide 3,5,5-trisubstituted imidazolones in very good yields via Ag-catalyzed insertion of the isocyano group into the N-H bond of the amine followed by in situ lactamization. The catalytic system also converts methyl 2-isocyanobenzoate and amines into quinazolin-4-ones in excellent yields.
A. Clemenceau, Q. Wang, J. Zhu, Org. Lett., 2017, 19, 4872-4875.

A mild methodology provides 4-arylthiazol-2(3H)-ones and 5,5'-methylenebis[4-arylthiazol-2(3H)-ones] using benign solvents. Products can be isolated using a precipitation-recrystallization protocol. The overall methodology can be scaled up to pilot plant level.
J. F. Ortuño, S. Poyraz, A. Belabbes, Ö. Kavas, S. Belveren, C. Altuğ, M. de Gracia Retamosa, F. Foubelo, C. M. Pask, J. M. Sansano, H. A. Döndaş, Synthesis, 2023, 55, 141-149.

The reaction of tert-Butyl nitrite with terminal aryl alkenes provides 3-aryl-1,2,4-oxadiazol-5(4H)-ones via a biradical reaction intermediate. Both of the nitrogen atoms and one oxygen originate from TBN, while the carbonyl oxygen is from moisture.
P. Sau, A. Rakshit, T. Alam, H. J. Srivastava, B. K. Patel, Org. Lett., 2019, 21, 4966-4970.

A gold-catalyzed [4 + 1] heterocyclization of nonactivated alkyne and hydroxamic acids provides 5-methyl-1,4,2-dioxazoles. This method offers high efficiency, simple operation, mild reaction conditions, and good functional group compatibility. Moreover, gram-scale synthesis and synthetic application toward bioactive molecular skeletons have been realized.
X.-L. He, X.-R. Ma, N. Yan, X.-W. Zhang, J. Org. Chem., 2023, 88, 433-441.

Pd(OAc)₂ catalyzes a cyclization of propargylic alcohols with tert-butyl nitrite at room temperature to provide 4-oxoisoxazoline N-oxides in good yields under mild conditions.
K.-W. Feng, Y.-L. Ban, P.-F. Yuan, W.-L. Lei, Q. Liu, R. Fang, Org. Lett., 2019, 21, 3131-3135.

A one-pot sequential N-acylation/dehydrative cyclization between ethyl carbazate and N-acylbenzotriazoles in the presence of Ph₃P-I₂ as a dehydrating agent enables a convenient synthesis of 5-substituted-2-ethoxy-1,3,4-oxadiazoles. Subsequent treatment with a stoichiometric amount of alkyl halides provides 3,5-disubstituted 1,3,4-oxadiazol-2(3H)-ones in very good yields.
S. Wet-osot, W. Phakhodee, M. Pattawarapan, J. Org. Chem., 2017, 82, 9923-9929.

A potassium-carbonate-mediated [3 + 2]-cycloaddition reaction of α-halohydroxamates with carbon disulfide provides functionalized rhodanine derivatives in very good yields. The present methodology offers a wide substrate scope as well as good functional group tolerance.
X. Lei, J. Feng, Q. Guo, C. Xu, J. Shi, Org. Lett., 2022, 24, 2837-2841.

A visible light-promoted three-component tandem annulation of α-bromoesters, amines, and aryl/alkyl isothiocyanates provides 2-iminothiazolidin-4-ones at room temperature in the absence of metal and photocatalyst. This [1 + 2 + 2] cyclization strategy offers broad substrate scope, excellent functional group tolerance, mild reaction conditions, step-economy, and simple operation.
W. Guo, M. Zhao, W. Tan, L. Zheng, K. Tao, L. Liu, X. Wang, D. Chen, X. Fan, J. Org. Chem., 2018, 83, 1402-1413.

Et₃N promotes a synthesis of 1,4-diarylisothiazolones in very good yields from α-keto-N-acylsulfoximines. This one-pot synthesis of isothiazolinones offers broad substrate scope and high atom economy.
N. Chakraborty, B. Das, D. Barik, K. K. Rajbongshi, B. K. Patel, J. Org. Chem., 2024, 89, 770-777.

An allenyl imide and alkynoates bearing good leaving groups are used as ketene precursors in tandem conjugate addition-elimination reactions promoted by nucleophilic phosphine catalysts. By utilizing thioamides as 1S,3N-bis-nucleophiles, [3+3] and [3+2] annulations provide rapid access to 1,3-thiazin-4-ones and 5-alkenyl thiazolones in high yields, respectively.
Y.-H. Wang, Z.-N. Zhao, S. J. Kalita, Y.-Y. Huang, Org. Lett., 2021, 23, 8147-8152.

A copper/PyBisulidine system catalyzes an enantioselective alkynylation of electrophilic pyrazole-4,5-diones with terminal alkynes in excellent yields and enantioselectivities under mild conditions. The nonlinear effect study showed that the catalytically active species was a monomeric catalyst and that the excess copper activated the alkynes through the π-system.
Y. Chai, P. Chen, R. Wu, J. Zhou, J. Ou, Y. Min, H. Wang, D. Zhang, H. Zhou, Y. Liu, J. Zhou, J. Org. Chem., 2023, 88, 13645-13654.

A convenient base-catalyzed three-component reaction between chalcones, isothiocyanates, and elemental sulfur provides thiazole-2-thiones in very good yields.
T. B. Nguyen, P. Retailleau, Org. Lett., 2021, 23, 5344-5348.

In a gold-catalyzed synthesis of bicyclic imidazoles, a highly electrophilic α-imino gold carbene intermediate can react with a weakly nucleophilic nitrile, which is used as the reaction solvent, to deliver the desired product rapidly in an overall bimolecular [2 + 2 + 1] cycloaddition and in good yield. The competing intramolecular azide-alkyne click reaction, although likely also catalyzed by gold, is minimized by using AuCl₃ as the catalyst.
Y. Xiao, L. Zhang, Org. Lett., 2012, 14, 4662-4665.

An iron-catalyzed [3 + 2] annulation from readily available oxime acetates with vinyl azides enables the synthesis of 2,4-substituted 2H-imidazoles via N-O/N-N bond cleavages and two C-N bond formations. This green reaction involving oxime acetate as internal oxidant, acetic acid, and nitrogen as byproducts can be performed under mild reaction conditions and needs no additives or ligands.
Z. Zhu, X. Tang, J. Li, X. Li, W. Wu, G. Deng, H. Jiang, Org. Lett., 2017, 19, 1370-1373.

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 dirhodium(II) complex catalyzes a reaction of 1-mesyl-1,2,3-triazoles and β-haloalkylcarbamates to provide a range of C2-substituted 2,3-dehydropiperazines. The reaction proceeds through an α-imino rhodium carbene 1,3-insertion into N-H followed by a base-mediated cyclization. Terminal alkynes can be used as substrate in a three-step, one-pot operation, forming the triazole in situ.
M. J. Nutt, J. W. Annear, K. D. Jones, G. R. Flematti, S. A. Moggach, S. G. Stewart, J. Org. Chem., 2023, 88, 11968-11979.

Intramolecular addition of tosylureas to allenes is highly syn-/anti-diastereoselective when employing a palladium or rhodium-based catalytic system and affords 1,3-cyclic ureas in excellent yields. The obtained tetrahydropyrimidinones are easily deprotected and modified.
A. G. A. Geissler, K. R. Riesterer, B. Breit, Org. Lett., 2021, 23, 9168-9172.

Fused bicyclic imidazole rings have been prepared in good yields by a sequence of the van Leusen three-component reaction and the ring-closing metathesis reaction.
V. Gracias, A. F. Gasiecki, S. W. Djuric, Org. Lett., 2005, 7, 3183-3186.

Palladium-catalyzed alkene carboamination reactions between acyclic N-allyl guanidines and aryl or alkenyl halides provide substituted 5-membered cyclic guanidines in good yield. This method allows access to a number of different cyclic guanidine derivatives in only two steps from readily available allylic amines.
B. P. Zavesky, N. R. Babij, J. A. Fritz, J. P. Wolfe, Org. Lett., 2013, 15, 5420-5423.

A silver-catalyzed hydroamination of tosyl-protected N-allylguanidines provides substituted cyclic guanidines in high yields. The reactions can be used for construction of quaternary stereocenters as well as both monocyclic and bicyclic guanidine products.
Z. J. Garlets, M. Silvi, J. P. Wolfe, Org. Lett., 2016, 18, 2331-2334.

An intramolecular transition-metal-free base-mediated hydroamination of propargylamine with isothiocyanates enables an atom-economical, regioselective synthesis of diversely substituted imidazole-2-thiones and spiro-cyclic imidazolidine-2-thiones in good yields via intramolecular 5-exo-dig cycloisomerization.
A. Ranjan, R. Yerande, P. B. Wakchaure, S. G Yerande, D. H. Dethe, Org. Lett., 2014, 16, 5788-5791.

A simple, commercially available iridium catalyst allows the use of sulfoxonium ylides as a carbene source for various intra- and intermolecular X-H bond insertions, including a practical ring-expansion strategy for lactams. The safety and stability of sulfoxonium ylides recommend them as preferable surrogates to traditional diazo ketones and esters.
I. K. Mangion, I. K. Nwamba, M. Shevlin, M. A. Huffman, Org. Lett., 2009, 11, 3566-3569.

Formation of iminophosphoranes in a Staudinger reaction and condensation with carbon disulfide followed by condensation with α-amino esters provides N-3-substituted 2-thiohydantoins.
S. Gosling, C. El Amri, A. Tatibouët, Synthesis, 2014, 46, 1079-1084.

An oxidative cascade cyclization strategy enables an unprecedented construction of thiazole-2-thiones from enaminones via a cascade of C(sp²)-H/C(sp²)-H bond sulfurations and C(sp³)-H bond thiocarbonylation. This transformation allows for the efficient synthesis of thiazole-2-thiones with broad tolerance in moderate to excellent yields from simple enaminones with elemental sulfur.
B. Zhan, D. Liu, Y. Sun, Y. Zhang, J. Feng, F. Yu, Org. Lett., 2021, 23, 3076-3082.

A molecular iodine-catalyzed oxidative cyclization of 2-aminopyridine/amidine and isothiocyanate via N-S bond formation enables the synthesis of N-fused and 3,4-disubstituted 5-imino-1,2,4-thiadiazole derivatives at ambient temperature. This transition-metal-free protocol provides a facile and highly efficient regiospecific synthesis of various 1,2,4-thiadiazole derivatives with good to excellent yields using inexpensive I₂ as a catalyst.
N. Tumula, N. Jatangi, R. K. Palakodety, S. Balasubramanian, M. Nakka, J. Org. Chem., 2017, 82, 5310-5316.

In situ derived acyclic and cyclic 1,2-diaza-1,3-dienes (DDs) undergo an interceptive [4 + 1] annulation with diazo esters (DEs) in the presence of inexpensive copper(II) chloride to yield mono-, bi-, and tricyclic 4,5-dihydropyrazole-5-carboxylic acid derivatives.
O. A. Attanasi, L. De Crescentini, G. Favi, F. Mantellini, S. Mantenuto, S. Nicolini, J. Org. Chem., 2014, 79, 8311-8338.

A novel palladium-catalyzed oxidative, intramolecular cyclocarbonylation provides an efficient and direct approach for the construction of valuable 1,3,4-oxadiazole-2(3H)-ones and their derivatives.
F. Ji, X. Li, W. Guo, W. Wu, H. Jiang, J. Org. Chem., 2015, 80, 5713-5718.

An unprecedented intermolecular cyclizative capture of the cyanamide anion and several nitrile oxides enables the synthesis of 1,2,4-oxadiazol-5(4H)-imines. Treatment of the imine products with concd. HCl furnishes 1,2,4-oxadiazol-5(4H)-ones.
S. V. Bhat, D. Robinson, J. E. Moses, P. Sharma, Org. Lett., 2016, 18, 1100-1103.

[RuCl₂(CO)₃]₂/dppp is a highly effective catalyst system for the intramolecular oxidative amination of various aminoalkenes in presence of K₂CO₃ and allyl acetate in N-methylpiperidine to give the corresponding cyclic imines and indoles in excellent yields.
T. Kondo, T. Okada, T.-A. Mitsudo, J. Am. Chem. Soc., 2002, 124, 186-187.

A copper-promoted 6-endo-trig cyclization of readily available β,γ-unsaturated hydrazones enables an efficient synthesis of a series of 1,6-dihydropyridazines with good yields, high functional group tolerance, and remarkable regioselectivity under mild conditions. Importantly, the 1,6-dihydropyridazines can be efficiently converted to biologically important pyridazines in the presence of NaOH.
Y.-Q. Guo, M.-N. Zhao, Z.-H. Ren, Z.-H. Guan, Org. Lett., 2018, 20, 3337-3340.

Cu(II)-catalyzed aerobic 6-endo-trig cyclizations provide 1,6-dihydropyridazines and pyridazines via the judicious choice of reaction solvent. Whereas 1,6-dihydropyridazines were obtained in good yields with MeCN as the reaction solvent, employment of AcOH directly afforded pyridazines in good yields.
Z. Fan, Z. Pan, L. Huang, J. Cheng, J. Org. Chem., 2019, 84, 4236-4245.

A highly efficient ruthenium-catalyzed stereospecific N-demethylative rearrangement of isoxazolidines gives synthetically useful N-H-1,3-oxazinanes. 1,3-Oxazinanes are useful building blocks, which can be converted to N-H-1,3-aminoalcohols in a subsequent step.
C.-Z. Yao, Z.-F. Xiao, X.-S. Ning, J. Liu, X.-W. Zhang, Y.-B. Kang, Org. Lett., 2014, 16, 5824-5826.

An electrochemical oxidative ring-opening of cyclopropylamides with alcohols provides 1,3-oxazines. This method avoids the use of external oxidants and offers good functional group tolerance. The substrate scope covers primary, secondary, and tertiary alcohols as well as (hetero)aryl amide-substituted cyclopropanes.
P.-C. Xu, S. Qian, X. Meng, Y. Zheng, S. Huang, Org. Lett., 2024, 26, 2806-2810.

Whereas the reaction of O-homoallyl benzimidates with Cu(OAc)₂ as oxidant involved an aza-Wacker-type intramolecular cyclization under Pd-catalysis to deliver 4-methylene-1,3-oxazines, K₂S₂O₈ as oxidant promotes a dimerization of O-homoallyl benzimidates to yield benzohydrazonates (azines).
R. A. Fernandes, A. J. Gangani, Org. Lett., 2022, 24, 7400-7404.

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.

Diboronic acid anhydride-catalyzed hydroxy-directed peptide bond formations enable a simple protocol for the concise synthesis of 2,5-diketopiperazines with hydroxymethyl functional groups in high yields. The sequential reactions consist of an intermolecular catalytic condensation reaction, a simple deprotection of the nitrogen-protecting group, and an intramolecular cyclization.
M. Koshizuka, K. Shinoda, K. Makino, N. Shimada, J. Org. Chem., 2023, 88, 6901-6910.

The use of cheap and innocuous reagents, such as NaClO₂, NaOCl, and catalytic amounts of TEMPO enables an environmentally friendly C(sp³)-H oxidation of piperazines and morpholines to 2,3-diketopiperazines and 3-morpholinones, respectively. In addition, by using a stoichiometric amount of TEMPO, 2-alkoxyamino-3-morpholinones can be prepared from morpholine derivatives.
D. Chamorro-Arenas, U. Osorio-Nieto, L. Quintero, L. Hernández-García, F. Sartillo-Piscil, J. Org. Chem., 2018, 83, 15333-15346.

A cyclization of N-alkenylamides catalyzed by iodoarenes under oxidative conditions enables the preparation of five-, six-, and seven-membered rings with a range of substitutions. Preliminary data from the use of chiral iodoarenes as precatalysts show that enantiocontrol is feasible.
A. Alhalib, S. Kamouka, W. J. Moran, Org. Lett., 2015, 17, 1453-1456.

Regioselective ring closing ene-yne metathesis provided an efficient access to different substituted 1-benzazepine scaffolds. Five- and six-membered lactams were efficiently prepared by ring-closing metathesis affording highly functionalizable compounds.
E. Benedetti, M. Lomazzi, F. Tibiletti, J.-P. Goddard, L. Fensterbank, M. Malacria, G. Palmisano, A. Penoni, Synthesis, 2012, 44, 3523-3533.

A wide screening of substrates in ring-closing metathesis reactions reveals the great efficiency of phosphabicyclononane (phoban)-containing ruthenium-based pre-catalysts. Comparison of the catalytic activities with Grubbs' first-generation pre-catalyst illustrates the key role of the Phoban ligand.
F. Boeda, H. Clavier, M. Jordaan, W. H. Meyer, S. P. Nolan, J. Org. Chem., 2008, 73, 259-263.

Aminocarbonyl Group Containing Hoveyda-Grubbs-Type Complexes: Synthesis and Activity in Olefin Metathesis Transformations
D. Rix, F. Caijo, I. Laurent, F. Boeda, H. Clavier, S. P. Nolan, M. Mauduit, J. Org. Chem., 2008, 73, 4225-4228.

Δ³-Aryl/heteroaryl substituted heterocycles via sequential Pd-catalysed termolecular cascade/ring closing metathesis (RCM)
H. A. Dondas, B. Clique, B. Cetinkaya, R. Grigg, C. Kilner, J. Morris, V. Sridharan, Tetrahedron, 2005, 61, 10652-10666.

An efficient enantioselective hydrazination/cyclization cascade reaction of α-substituted isocyanoacetates to azodicarboxylates is catalyzed by a squaramide catalyst derived from Cinchona alkaloid. The reaction affords optically active 1,2,4-triazolines in excellent yields and very good enantioselectivities under mild conditions.
M-X. Zhao, H.-L. Bi, H. Zhou, H. Yang, M. Shi, J. Org. Chem., 2013, 78, 9377-9382.

Organic phosphine-catalyzed [4 + 2] annulation of ethyl 2-(substituted-methyl)-2,3-butadienoates as 1,4-dipole synthons with N-tosylimines gave ethyl 2,6-cis-disubstituted-1-(4-tosyl)-1,2,5,6-tetrahydro-pyridine-3-carboxylates in excellent yields with complete regioselectivity and high diastereoselectivity.
X.-F. Zhu, J. Lan, O. Kwon, J. Am. Chem. Soc., 2003, 125, 4716-4717.

Fully substituted 4-aminopyrrolones are easily accessed starting from imines, ketones, or α-bromophenyl acetonitriles. Imines are reacted with KCN/NH₄Cl, whereas ketones are transformed to the desired α-amino nitriles using a modified Strecker reaction. Reaction with a suitable acyl halide produces the corresponding amides. Ttreatment of these amides with ethanolic KOH gives 4-amino-1H-pyrrol-2(5H)-one derivatives in good yields.
H. Zali-Boeini, M. Mobin, K. Hajibabaei, M. Ghani, J. Org. Chem., 2012, 77, 5808-5812.

Pentafluorophenyl anion and trifluoromethyl anion as leaving groups enable a new synthesis of 1,2,4-oxadiazol-5-ones from amidoximes using pentafluorobenzoyl chloride or trifluoroacetic anhydride (TFAA) as a double acylating agent.
T. Gerfaud, H.-L. Wei, L. Neuville, J. Zhu, Org. Lett., 2011, 13, 6172-6175.

Ring-closing olefin metathesis (RCM)/elimination and RCM/oxidation/deprotection of nitrogen-containing dienes are the key processes of new synthetic routes to substituted 3-hydroxypyridines. An application of RCM/oxidation/deprotection allows the synthesis of 3-aminopyridine derivatives.
K. Yoshida, F. Kawagoe, K. Hayashi, S. Horiuchi, T. Imamoto, A. Yanagisawa, Org. Lett., 2009, 11, 515-518.

A rhodium-catalyzed cycloisomerization converts various acyclic enynes to their cyclic diene isomers with endoselectivity. Two different catalyst systems have been developed, which are effective in promoting the C-C bond-forming cyclization of enynes to furnish carbo- and heterocycles in good to excellent yield. The mechanism is discussed.
H. Kim, C. Lee, J. Am. Chem. Soc., 2005, 127, 10180-10181.

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.

A Brønsted acid accelerated oxidative radical annulation of sulfonyl hydrazones with simple olefins provides six-membered heterocycles. The method offers a rapid and efficient approach to tetrahydropyridazines which are key structural motifs in pharmaceutically active compounds.
X. Zhong, J. Lv, S. Luo, Org. Lett., 2016, 18, 3150-3153.

Pd-catalyzed asymmetric carboetherification of γ,δ-alkenyl oximes with (hetero)aryl and alkenyl halides in the presence of (R)-DTBM-SegPhos(O) enables a straightforward synthesis of highly enantioenriched 5,6-dihydro-4H-1,2-oxazines. Alternatively, commercially available (R)-DTBM-SegPhos can be oxidized in situ in the presence of water without erosion of enantiocontrol.
N. Li, B. Sun, S. Liu, J. Zhao, Q. Zhang, Org. Lett., 2020, 22, 190-193.

The combination of NaI/PPh₃/TMEDA mediates a direct C-H alkylation of azauracils using N-(acyloxy)pthalimides (NHPIs) as readily available alkyl surrogates under visible light irradiation. This transition-metal-free reaction offers a broad scope, scalability, and appreciable functional group tolerance.
S. P. Panda, S. K. Hota, R. Dash, L. Roy, S. Murarka, Org. Lett., 2023, 25, 3739-3744.

A mild and highly efficient AgOTf catalyzed [3,3] sigmatropic rearrangement/1,3-H shift/6π aza-electrocyclization cascade reaction of N-propargylic hydrazones provides arious polysubstituted 1,6-dihydropyridazines with high selectivity.
Z.-C. Ding, L-C. Ju, Y. Yang, X.-M. An, Y.-B. Zhou, R.-H. Li, H.-T. Tang, C.-K. Ding, Z.-P. Zhan, J. Org. Chem., 2016, 81, 3936-3941.

The reaction of in situ formed acyl isocyanates with amidines provides disubstituted 1,3,5-triazinones with a low production cost and a simple workup procedure. Chlorination and a further coupling reaction with various nucleophiles gives unsymmetrical trisubstituted 1,3,5-triazines bearing diverse functional groups.
H. Liang, G. Li, L. Zhang, G. Wang, M. Song, H. Li, B. Yuan, Org. Lett., 2021, 23, 5821-5825.

The combination of palladium and photoredox catalysis enables an aerobic intramolecular oxidative carbonylation of enamides. The dual catalytic system provides a mild and environmentally friendly method for the synthesis of 1,3-oxazin-6-ones without the use of a stoichiometric amount of hypervalent metal salts.
K. Liu, M. Zou, A. Lei, J. Org. Chem., 2016, 81, 7088-7092.

In a cascade β-C-H bond trifluoromethylation/C(sp³)-F bond activation/hydrolysis reaction of enamides with Togni’s reagent, the CF₃ group acts as a CO surrogate to provide 1,3-oxazin-6-ones in good yields, including synthetically or pharmaceutically important compounds, which are difficult to access by known methods.
P. Song, P. Yu, J.-S. Lin, Y. Li, N.-Y. Yang, X.-Y. Liu, Org. Lett., 2017, 19, 1330-1333.

An allenyl imide and alkynoates bearing good leaving groups are used as ketene precursors in tandem conjugate addition-elimination reactions promoted by nucleophilic phosphine catalysts. By utilizing thioamides as 1S,3N-bis-nucleophiles, [3+3] and [3+2] annulations provide rapid access to 1,3-thiazin-4-ones and 5-alkenyl thiazolones in high yields, respectively.
Y.-H. Wang, Z.-N. Zhao, S. J. Kalita, Y.-Y. Huang, Org. Lett., 2021, 23, 8147-8152.

A double aza-Michael addition of anilines to water-insoluble divinyl sulfones on the surface of water provides solid cyclic β-amino sulfones as easily separable products in excellent yields upon microwave irradiation at 150°C for 10 min. This atom-efficient method converts a broad range of amines and offers good functional group tolerance. Acyclic β-amino sulfones can also be synthesized.
S. Saha, A. Chatterjee, M. Banerjee, J. Org. Chem., 2023, 88, 15358-15366.

A facile switchable regioselective 7-endo or 6-exo iodocyclization of O-homoallyl benzimidates provides various iodo-substituted 1,3-oxazines and tetrahydro-1,3-oxazepines in a controllable manner under mild conditions and with excellent functional group compatibility. The products can further undergo substitution reactions to afford a series of functionalized heterocyclic molecules.
T.-Y. Cao, L. Qi, L.-J. Wang, J. Org. Chem., 2023, 88, 3035-3045.

A facile switchable regioselective 7-endo or 6-exo iodocyclization of O-homoallyl benzimidates provides various iodo-substituted 1,3-oxazines and tetrahydro-1,3-oxazepines in a controllable manner under mild conditions and with excellent functional group compatibility. The products can further undergo substitution reactions to afford a series of functionalized heterocyclic molecules.
T.-Y. Cao, L. Qi, L.-J. Wang, J. Org. Chem., 2023, 88, 3035-3045.

A photochemical rearrangement of N-vinylpyrrolidinones provides azepin-4-ones in good yields. This transformation allows for the conversion of readily available pyrrolidinones and aldehydes to densely functionalized azepane derivatives in a facile two-step procedure.
S. M. Thullen, D. M. Rubush, T. Rovis, Synlett, 2017, 28, 2755-2758.

Under very mild conditions employing BBr₃ as a Lewis acid catalyst and P₂O₅ as an additive, tertiary enamides that contain a formyl group underwent highly efficient and scalable intramolecular cyclic condensation to afford diverse 2,3-dihydro-1H-azepine and 1H-azepin-2(3H)-one derivatives in very good yields.
W. Zhu, L. Zhao, M.-X. Wang, J. Org. Chem., 2015, 80, 12047-12057.

The use of cationic silver (AgSbF₄) as a catalyst for intra- and intermolecular alkyne-carbonyl coupling is described.
J. U. Rhee, M. J. Krische, Org. Lett., 2005, 7, 2493-2495.

An effective route to novel 5-hydroxy-1,5-dihydro-2H-pyrrol-2-one is described which involves the reaction of an enamine, derived from addition of a secondary amine to dibenzoylacetylene, with an arylsulfonyl isocyanate.
A. Alizadeh, F. Movahedi, H. Masrouri, L.-G. Zhu, Synthesis, 2006, 3431-3436.

A formal [3 + 3] cycloaddition reaction between azides and in situ formed azaoxyallyl cations provides 1,2,3,4-tetrazines in good yields under mild conditions.
X. Xu, K. Zhang, P. Li, H. Yao, A. Lin, Org. Lett., 2018, 20, 1781-1784.

Trialkylsilyl triflates effect cyclization of ester-imides and diesters. Trapping of the in situ generated, nucleophilic ketene acetal is a key aspect of the transformation. In many instances the levels of diastereoselectivity are very high. Mechanistic points are inferred from spectroscopic observations.
T. R. Hoye, V. Dvornikovs, E. Sizova, Org. Lett., 2006, 8, 5089-5091.

A three-component condensation gave 2-amino-4H-1,3-oxazines or 2-amino-4H-1,3-thiazines from alkynes, urea or thiourea, and aldehydes.
S. Huang, Y. Pan, Y. Zhu, A. Wu, Org. Lett., 2005, 7, 3797-3799.

tert-Butyl hypoiodite is a mild and powerful reagent for the cyclization of N-alkenylamides leading to various N-heterocycles. N-alkenylsulfonamides gave three- to six-membered saturated N-heterocycles in good yields, whereas alkenylbenzamide derivatives afforded N-, O- or N-, S-heterocycles.
S. Minakata, Y. Morino, Y. Oderaotoshi, M. Komatsu, Org. Lett., 2006, 8, 3335-3337.

An aza-Michael-addition/cyclization/condensation reaction sequence starting from sulfonimidamides and propargyl ketones provides 1,2,6-thiadiazine 1-oxides. These three-dimensional S,N-heterocycles have been further functionalized by standard cross-coupling reactions, selective bromination of the heterocyclic ring, and conversion into a β-hydroxy substituted derivative.
J.-H. Schöbel, M. T. Passia, N. A. Wolter, R. Puttreddy, K. Rissanen, C. Bolm, Org. Lett., 2020, 22, 2702-2706.

A three-component condensation gave 2-amino-4H-1,3-oxazines or 2-amino-4H-1,3-thiazines from alkynes, urea or thiourea, and aldehydes.
S. Huang, Y. Pan, Y. Zhu, A. Wu, Org. Lett., 2005, 7, 3797-3799.

A powerful aza-Prins cyclization in combination with the Peterson-type elimination reaction provides seven-membered unsaturated azacycles (tetrahydroazepines) under mild reaction conditions and using iron(III) salts as sustainable catalysts. In a single reaction step, a C-N, C-C bond and an endocyclic double bond are formed.
V. Sinka, I. Fernández, J. I. Padrón, J. Org. Chem., 2022, 87, 11735-11742.

Use of the Ramberg-Bäcklund Rearrangement for the Synthesis of Medium and Large Heterocyclic Alkenes:  Stereoselective Olefin Formation
D. I. MaGee, E. J. Beck, J. Org. Chem., 2000, 65, 8367-8371.

Stereocontrolled Construction of N-Heterocycles Preparation of Heteraromatics Asymmetric Hetero-Diels-Alder Reactions N-Heterocycle Construction by Alkene Metathesis Diastereoselective and Enantioselective Construction of Aza-Heterocycles New Routes to Heterocycles