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Synthesis of O-Heterocycles

Synthesis of


benzo-fused O-Heterocycles: benzofurans, coumarins, benzoxazoles, chromones, flavones, and more


Cyclic ethers: epoxides, oxetanes, tetrahydrofurans, tetrahydropyrans, morpholines, and more


Lactols


Lactones: butenolides, 5,6-dihydropyran-2-ones, 3,4-dihydropyran-2-ones, dihydropyranones, and more


Oxaziridines, 1-oxa-2-azacyclopropane, 1,2-oxazacyclopropane


Acetals: 1,3-dioxolanes, and more


Oxathioacetals


Oxetenes


Oxetan-3-ones, 3-oxetanones


1,3-dioxolanes


Dioxolanones, carbonates


Oxazolidinones


Oxazolidines


Isoxazolidines


2,5-Dihydrofurans


2,3-Dihydrofurans


Furans


Butenolides


3(2H)-Furanones


2-Isoxazolines


3-Isoxazolines


4-Isoxazolines


2-Oxazolines


3-Oxazolines


Oxazoles


Isoxazoles


1,2,4-Oxadiazoles


2-Oxazolones


1,3,4-Oxadiazoles


1,2,5-Oxadiazoles


3,4-Dihydro-2H-pyrans, dihydropyrans


2H-Pyrans


4H-Pyrans


2-Pyrones


5,6-Dihydropyran-2-ones


3,4-Dihydropyran-2-ones


4-Pyrones


2,3-dihydro-4H-pyran-4-ones


2H-Pyran-5-ones


3,4-Dihydro-2H-1,4-oxazines


Recent Literature


An efficient and highly enantioselective Payne-type oxidation of N-sulfonyl imines exhibits broad substrate generality and unique chemoselectivity based on the combined use of hydrogen peroxide and trichloroacetonitrile under the catalysis of P-spiro chiral triaminoiminophosphorane.
D. Uraguchi, R. Tsutsumi, T. Ooi, J. Am. Chem. Soc., 2013, 135, 8161-8164.


A cobalt-catalyzed peroxidation of silyl enol ethers with molecular oxygen and triethylsilane provides silyl monoperoxyketals in good yield. These compounds serve as precursors to peroxycarbenium ions, which undergo annulations to provide 1,2-dioxolanes.
B. Hurlocker, M. R. Miner, K. A. Woerpel, Org. Lett., 2014, 16, 4280-4283.


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.


A nickel-catalyzed double carboxylation of internal alkynes proceeds under CO2 (1 atm) at room temperature in the presence of Zn powder as a reducing reagent and MgBr2 as an indispensable additive. Various internal alkynes could be converted to the corresponding maleic anhydrides in good to high yields.
T. Fujihara, Y. Horimoto, T. Mizoe, F. B. Sayyed, Y. Tani, J. Terao, S. Sakaki, S. Tsuji, Org. Lett., 2014, 16, 4960-4963.


An iron-catalyzed α-C(sp3)-H activation of cyclic and acyclic ethers provides an efficient and green method for the synthesis of mixed acetals in very good yields. The robustness of this protocol is demonstrated by the late-stage oxidation of a structurally complex natural product.
W. Han, L. Cheng, H. Zhao, Synlett, 2020, 31, 1400-1403.


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.


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.


An expedient and reliable method for accessing reactive α-oxo gold carbenes via gold-catalyzed intermolecular oxidation of terminal alkynes offers a safe and economical alternative to strategies based on diazo substrates. Its synthetic potential is demonstrated by expedient preparation of dihydrofuran-3-ones containing a broad range of functional groups.
L. Ye, L. Cui, G. Zhang, L. Zhang, J. Am. Chem. Soc., 2010, 132, 3258-3259.


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.


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.


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 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.


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.


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.


An enantioselective intermolecular Prins reaction of styrenes and paraformaldehyde provides 1,3-dioxanes, using confined imino-imidodiphosphate (iIDP) Brønsted acid catalysts via a concerted, highly asynchronous addition of an acid-activated formaldehyde oligomer to the olefin. The enantioenriched 1,3-dioxanes can be transformed into the corresponding optically active 1,3-diols.
C. D. Díaz-Oviedo, R. Maji, B. List, J. Am. Chem. Soc., 2021, 143, 20598-20604.


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.


Diastereoselective Synthesis of 2,6-Disubstituted Tetrahydropyranones via Prins Cyclization of 3-Bromobut-3-en-1-ols and Aldehydes
S. K. Bora, S. Shit, A. K. Sahu, A. K. Saikia, J. Org. Chem., 2023, 88, 3012-3021.


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.


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 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.


The electrochemically induced catalytic multicomponent reaction of cyclic 1,3-diketones, aldehydes and malononitrile in alcoholic solvents results in the formation of substituted 5,6,7,8-tetrahydro-4H-chromenes in excellent yields.
M. N. Elinson, A. S. Dorofeev, S. K. Feducovich, S. V. Gorbunov, R. F. Nasybullin, F. M. Miloserdov, G. I. Nikishin, Eur. J. Org. Chem., 2006, 4335-4339.


A nickel-catalyzed cycloaddition of aziridines with isocyanates proceeded smoothly to give iminooxazolidine derivatives in good yields. A longer reaction time allowed the isomerization of the iminooxazolidine to the corresponding imidazolidinone derivatives.
T. Munegumi, I. Azumaya, T. Kato, H. Masu, S. Saito, Org. Lett., 2006, 8, 379-382.


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 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.


The merger of photoactivation and asymmetric Pd catalysis enables an enantioselective [5+2] cycloaddition of vinylethylene carbonates and α-diazoketones to provide 7-membered lactones bearing challenging chiral quaternary stereocenters.
Y. Wei, S. Liu, M.-M. Li, Y. Li, Y. Lan, L.-Q. Lu, W.-J. Xiao, J. Am. Chem. Soc., 2019, 141, 133-137.

Stereocontrolled Construction of O-Heterocycles
Asymmetric Hetero-Diels-Alder Reactions
O-Heterocyclic Construction by Alkene Metathesis
Stereoselective Construction of Oxygen Heterocycles