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.
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.
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.
A gold-catalyzed oxidative cyclization/nucleophilic addition/C-C bond
cleavage reaction of ynones with various nucleophiles provides highly
functionalized linear N-Ts amides with broad substrate scope, high
efficiency, and general tolerance of functional groups. A wide range of
nucleophiles such as alcohols, water, and amines including aryl and alkyl amines
are compatible with the method.
M. Lu, Y. Liu, Org. Lett., 2023, 25,
8105-8109.
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.
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 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.