Pyridine N-oxide and derivatives

Recent Literature

Gold-catalyzed intermolecular oxidation enables an efficient conversion of various terminal alkynes into the corresponding α-acetoxy ketones in the presence of 8-methylquinoline 1-oxide as the oxidant. The reaction probably proceeds through an α-oxo gold carbene intermolecular O-H insertion.
C. Wu, Z. Liang, D. Yan, W. He, J. Xiang, Synthesis, 2013, 45, 2605-2611.

CpRuCl(PPh₃)₂ catalyzes reactions of terminal alkynes with primary and secondary amines to afford the corresponding amides in the presence of 4-picoline N-oxide. The reactions occur in chlorinated solvent and aqueous medium, showing applications in peptide chemistry.
A. Álvarez-Pérez, M. A. Esteruelas, S. Izquierdo, J. A. Varela, C. Saá, Org. Lett., 2019, 21, 5346-5350.

By rendering the α-position of amides electrophilic through a mild and chemoselective umpolung transformation, a broad range of widely available oxygen, nitrogen, sulfur, and halogen nucleophiles can be used to generate α-functionalized amides.
C. R. Gonçalves, M. Lemmerer, C. J. Teskey, P. Adler, D. Kaiser, B. Maryasin, L. González, N. Maulide, J. Am. Chem. Soc., 2019, 141, 18437-18443.

Flexible and chemoselective methods for the transition-metal-free oxidation of amides provide α-keto amides and α-hydroxy amides. These highly valuable motifs are accessed in good to excellent yields and stereoselectivities with high functional group tolerance.
A. de la Torre, D. Kaiser, N. Maulide, J. Am. Chem. Soc., 2017, 139, 6578-6581.

A unique Au-allenylidene pathway enables an in situ formation of highly unsaturated alkylidene ketenes from propargyl alcohol derivatives. A subsequent trapping with a broad range of nucleophiles such as alcohols, phenols, water, amines, and sulfoximines in the presence of an N-oxide provides α,β-unsaturated drug and natural product derivatives.
X. Sun, X. Duan, N. Zheng, W. Song, Org. Lett., 2023, 25, 2798-2805.

2,3-Dichloropyridine N-oxide as oxygen transfer reagent enables gold(I)-catalyzed oxidation of alkynes to 1,2-dicarbonyls in the absence of any acid additives and under mild conditions. The developed strategy is also effective for ynamides, alkynyl ethers/thioethers, and substrates bearing highly acid-sensitive groups. A one-pot heterocyclization provides six-membered azaheterocycles.
A. Yu. Dubovtsev, N. V. Shcherbakov, D. V. Dar'in, V. Yu. Kukushkin, J. Org. Chem., 2020, 85, 745-757.

The use of pyridine-N-oxides as oxidants under molecular iodine catalysis enables a rapid, metal-free dioxygenation of ynamides. Furthermore, this protocol could be extended to nonactivated alkynes, such as diarylacetylenes, to provide various benzil derivatives.
S. W. Kim, T.-W. Um, S. Shin, J. Org. Chem., 2018, 83, 4703-4711.

An efficient gold(I)-catalyzed oxidation of COR₂-functionalized internal alkynes provides α,β-diketoesters, 1,2,3-triketones, and α,β-diketoamides in good yields under mild conditions in the presence of 2,6-dichloropyridine N-oxide. The utility of these compounds was demonstrated by facile one-pot syntheses of azaheterocycles.
A. Y. Dubovtsev, D. V. Dar'in, V. Y. Kukushkin, Org. Lett., 2019, 21, 4116-4119.

The combination of readily accessible starting materials provide a surrogate for toxic difluorophosgene (COF₂) gas that enables a synthesis of carbamoyl fluorides. This protocol does not require the use of pre-functionalized substrates, the preparation of light-, temperature-, and/or moisture-sensitive chemicals, or the application of explosive fluorinating reagents.
D. Cadwaller, T. R. Tiburcio, G. A. Cieszynski, C. M. Le, J. Org. Chem., 2022, 87, 11457-11468.

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 general synthesis of various oxetan-3-ones uses readily available propargylic alcohols as substrates and proceeds without the exclusion of moisture or air. The facile formation of the strained oxetane ring provides strong support for the intermediacy of α-oxo gold carbenes. This safe and efficient generation of gold carbenes offers an entry into α-oxo metal carbene chemistry without using hazardous diazo ketones.
L. Ye, W. He, L. Zhang, J. Am. Chem. Soc., 2010, 132, 8550-8551.

A Rh-catalyzed oxygenative carbofunctionalization of terminal alkynes provides cyclic carboxylic acid derivatives. The generation of a disubstituted Rh vinylidene complex upon C-C bond formation at the terminal alkyne is followed by a transfer oxygenation. The newly formed rhodium-complexed ketene intermediate reacts with a variety of heteroatom nucleophiles to give the desired products.
D.-K. Kim, M. Keum, H. Yun, I. Kim, J. M. Joo, C. Lee, Org. Lett., 2023, 25, 1889-1894.

Catalytic generation of a ketene species directly from a terminal alkyne in the presence of a Rh(I) catalyst and 4-picoline N-oxide provides a novel and efficient entry to the Staudinger synthesis of β-lactams with high trans diastereoselectivity under mild conditions. Mechanistic studies suggest that the reaction proceeds through a metalloketene rather than free ketene intermediate.
I. Kim, S. W. Roh, D. G. Lee, C. Lee, Org. Lett., 2014, 16, 2482-2485.

A gold(I)-catalyzed oxidative rearrangement of propargyl alcohols provides an efficient and selective route to 1,3-diketones under mild conditions in the presence of pyridine-N-oxides as external oxidants.
A. S. K. Hashmi, T. Wang, S. Shi, M. Rudolph, J. Org. Chem., 2012, 77, 7761-7767.

A metal-free C≡C bond cleavage of terminal alkynes in the presence of tBuONO as a powerful nitrogenating agent provides a vast range of nitriles containing aryl, heteroaryl, and natural product derivatives.
U. Dutta, D. W. Lupton, D. Maiti, Org. Lett., 2016, 18, 860-863.

An MCM-41-immobilized phosphine-gold(I) complex as catalyst enables a [2 + 2 + 1] annulation of terminal alkynes, nitriles, and oxygen atoms using 8-methylquinoline N-oxide as oxidant under mild conditions to provide 2,5-disubstituted oxazoles in very good yields with broad substrate scope. The heterogeneous catalyst can easily be recovered by simple filtration and recycled for at least eight times without significant loss of activity.
W. Yang, R. Zhang, F. Yi, M. Cai, J. Org. Chem., 2017, 82, 5204-5211.

A facile gold-catalyzed heterocyclization provides 2-amino-1,3-oxazoles functionalized at the nitrogen atom as well as at the fifth position of the heterocyclic ring in good to moderate yields. The reaction is based on intermolecular trapping of intermediate α-oxo gold carbenes with various cyanamides.
V. A. Rassadin, V. P. Boyarskiy, V. Yu. Kukushkin, Org. Lett., 2015, 17, 3502-3505.

A gold(I)-catalyzed oxidative annulation involving ynamides, nitriles, and 2,3-dichloropyridine N-oxide provides 5-amino-1,3-oxazoles. In addition, the use cyanamides instead of nitriles provides difficult-to-obtain 2,5-diaminooxazoles. The process is feasible for wide ranges of ynamides or nitriles, and it can be conducted in gram scale.
D. P. Zimin, D. V. Dar'in, Y. Yu. Kukushkin, A. Y. Dubovtsev, J. Org. Chem., 2021, 86, 1748-1757.

An efficient copper-catalyzed oxidative cyclization of diynes as readily available substrates provides a range of functionalized γ-lactams. This copper-catalyzed oxidative process proceeds through an alkyne oxidation, carbene/alkyne metathesis, and donor-donor carbene oxidation sequence. This simple method offers high flexibility and mild reaction conditions.
T.-T. Zhang, K.-F. Wei, G.-X. Ru, X.-H. Zhu, L-X. Xie, W.-B. Shen, Synlett, 2023, 34, 149-152.

A Hg(OTf)₂-catalyzed N-oxide addition to alkynes forms an enolonium species, that can undergo intramolecular nucleophilic attack by hydroxyl or amino groups, providing various coumaran-3-ones and indolin-3-ones via an enolate umpolung reactivity.
Z. Rong, W. Hu, N. Dai, G. Qian, Org. Lett., 2020, 22, 3245-3250.

A Brønsted acid-catalyzed oxidative C-H functionalization of alkynyl thioethers provides valuable isothiochroman-3-ones in good yields under mild reaction conditions. This metal-free reaction offers a broad substrate scope and wide functional group tolerance.
Y.-Q. Zhang, X.-Q. Zhu, Y.-B. Chen, T.-D. Tan, M.-Y. Yang, L.-W. Ye, Org. Lett., 2018, 20, 7721-7725.

Gold-catalyzed oxidative cyclizations of o-(alkynyl)phenyl propargyl ether derivatives enable a convenient synthesis of functionalized 1H-isochromene and 2H-pyran derivatives via highly regioselective oxidation, followed by 1,2-migration of an enynyl group and nucleophlic addition. Oxidative cleavage of the exocyclic double bond of the obtained 1H-isochromenes provides isocoumarins.
J. Zhao, W. Xu, X. Xie, N. Sun, X. Li, Y. Liu, Org. Lett., 2018, 20, 5461-5465.