Categories: C-N Bond Formation >
Synthesis of amides
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Recent Literature
The key to the success of a general catalytic procedure for the cross-coupling
of primary amides and alkylboronic acids was the identification of a mild base
(NaOSiMe3) and oxidant (di-tert-butyl peroxide) to promote the
copper-catalyzed reaction in high yield. This transformation provides a facile,
high-yielding method for the monoalkylation of amides.
S. A. Rossi, K. W. Shimkin, Q. Xu, L. M. Mori-Quiroz, D. A. Watson, Org. Lett., 2013,
15, 2314-2317.
Trialkyl phosphates are inexpensive and stable at room temperature, under
air, and are easy to handle. Mild, straightforward and powerful methods for
nucleophilic alkylation of various N-, O-, C- and S-nucleophiles
using readily available trialkyl phosphates proceed smoothly in excellent yields.
Stereoselective transfer of secondary alkyl groups have also been achieved with
inversion of configuration.
A. Banerjee, T. Hattori, H. Yamamoto, Synthesis, 2023,
55,
315-332.
The quaternary ammonium salts PhMe3NI and PhEt3NI are safe, nontoxic, and easy-to-handle
reagents for absolutely monoselective N-alkylations of amides and
NH indoles. These convenient reactions offer high yields, high functional group tolerance,
and especially excellent monoselectivity for amides. Late-stage methylations of
a broad range of bioactive compounds are also described.
J. Templ, E. Gjata, F. Getzner, M. Schnürch, Org. Lett.,
2022, 24, 7315-7319.
N-Heterocyclic carbene-phosphine iridium complexes (NHC-Ir) are highly reactive
catalysts for N-monoalkylation of amides with alcohols via hydrogen transfer.
The reaction gave products in high isolated yields for a wide range of
substrates with low catalyst loading and in short reaction times.
S. Kerdphon, X. Quan, V. S. Parihar, P. G. Andersson, J. Org. Chem.,
2015,
80, 11529-11537.
K3PO4 mediates a mild sustainable protocol for the
coupling of primary alkyl chlorides and bromides with amides. The reaction does
not require strongly basic conditions, high temperatures, or the addition of an
organometallic catalyst, thereby enabling access to a remarkably orthogonal
scope of alkylated amide products in good yields.
J. P. Hibbard, J. G. Yam, E. B. Alsalek, A. Bahmonde, J. Org. Chem., 2022, 87,
12036-12040.
Tetramethylammonium fluoride (TMAF) enables a direct and selective
methylation of various amides, indoles, pyrroles, imidazoles, alcohols, and
thiols. The method is characterized by operational simplicity, wide scope, and
ease of purification.
H.-G. Cheng, M. Pu, G. Kundu, F. Schoenebeck,
Org. Lett., 2020, 22, 331-334.
The use of a ruthenium(II) catalyst enables an efficient synthesis of N-methylated amides
in the presence of methanol. In addition, a tandem
C-methylation and N-methylation provided α-methyl
N-methylated amides.
B. Paul, D. Panja, S. Kundu,
Org. Lett., 2019, 21, 5843-5847.
Rh(III) catalyzes an intermolecular anti-Markovnikov hydroamidation of
unactivated alkenes with dioxazolone amidating reagents and isopropanol as
hydride source under mild conditions. The reaction tolerates a wide range of
functional groups and efficiently converts also electron-deficient, styrenes,
and 1,1-disubstituted alkenes to their corresponding linear amides.
N. Wagner-Carlberg, T. Rovis, J. Am. Chem. Soc.,
2022, 144, 22426-22432.
Solvent-free, base-free microwave-mediated (Cp*IrCl2)2-catalyzed
conditions for the N-alkylation of amides with a series of primary and
secondary alcohols produce high yields of N-alkyl arylamides and N-alkyl
alkylamides.
T. D. Apsunde, M. L. Trudell, Synthesis, 2014, 46,
230-234.
A photoinduced, copper-catalyzed monoalkylation of primary amides couples a
broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone)
with unactivated secondary (and hindered primary) alkyl bromides and iodides.
The method is compatible with a variety of functional groups, such as an olefin,
a carbamate, a thiophene, and a pyridine, and it has been applied to the
synthesis of an opioid receptor antagonist.
H.-Q. Do, S. Bachman, A. C. Bissember, J. C. Peters, G. C. Fu, J. Am. Chem. Soc., 2014,
136, 2162-2167.
An efficient copper-catalyzed amidation of benzylic hydrocarbons and inactive
aliphatic alkanes with simple amides proceeded smoothly without any ligand. A
wide range of N-alkylated aromatic and aliphatic amides, sulfonamides,
and imides were synthesized in good yields.
H.-T. Zeng, J.-M. Huang, Org. Lett.,
2015,
17, 4276-4279.
Cu2O/N,N'-bis(thiophen-2-ylmethyl)oxalamide is an effective
catalyst system for Goldberg amidation with inferior reactive (hetero)aryl
chlorides. The reaction converts a variety of functionalized (hetero)aryl
chlorides and a wide range of aromatic and aliphatic primary amides in very good
yields. Furthermore, the arylation of lactams and oxazolidinones is achieved.
S. De, J. Yin, D. Ma, Org. Lett.,
2017, 19, 4864-4867.
Boron-derived Lewis acids effectively promote the coupling of amide nucleophiles
to various aryl and heteroaryl
chlorides using a bulky Pd-NHC catalyst. It's proposed that boron-imidates form
under the basic reaction conditions that aid coordination of nitrogen to Pd(II),
which is rate limiting, and directly delivers the intermediate for reductive
elimination.
S. Sharif, J. Day, H. N. Hunter, Y. Lu, D. Mitchell, M. J. Rodriguez, M. G.
Organ, J. Am. Chem. Soc., 2017,
139, 18436-18439.
An extremely general, experimentally simple, and inexpensive catalyst system for
the amidation of aryl halides and the N-arylation of a wide variety of
heterocycles has been developed. This Cu-based catalyst system provides an
excellent complement to the Pd-catalyzed methodology that has already been
utilized in a number of applications.
A. Klapars, J. C. Antilla, X. Huang, S. L. Buchwald, J. Am. Chem. Soc., 2001,
123, 7727-7729.
The use of monodentate ligands that possess a methyl group ortho to
the phosphorus center allows the coupling of various aryl and heteroaryl
chlorides with various amides in high yield. These ligands can prevent the
formation of the κ2-amidate complexes and thereby generate more
stable catalysts for the amination of aryl chlorides.
T. Ikawa, T. E. Barder, M. R. Biscoe, S. L. Buchwald, J. Am. Chem. Soc., 2007,
129, 13001-13007.
A catalyst, based on a biarylphosphine ligand, for the Pd-catalyzed
cross-coupling reactions of amides and aryl mesylates allows the transformation
of an array of aryl and heteroaryl mesylates into the corresponding N-aryl
amides in good yields.
K. Dooleweerdt, B. P. Fors, S. L. Buchwald, Org. Lett., 2010,
12, 2350-2353.
The Xantphos/Pd-catalyzed intermolecular coupling of aryl halides and amides
displays good functional
group compatibility, and the desired C-N bond forming process proceeds in good
to excellent yields. The
arylation of sulfonamides, oxazolidinones, and ureas was found to be highly dependent on reaction
concentrations and catalyst loadings.
J. Yin, S. L. Buchwald, J. Am. Chem. Soc., 2002,
124, 6043-6048.
A mild and highly efficient direct synthesis of formanilides from structurally
varied arylboronic acids involves a copper-catalyzed Chan-Lam coupling reaction
between arylboronic acids and formamide in the presence of a base at room
temperature. The strategy offers a valid and practical alternative to existing
transformations especially as arylboronic acids are easily accessible, stable,
and diversified substrates.
V. P. Srivastava, D. K. Yadav, A. K. Yadav, G. Watal, L. D. S. Yadav, Synlett, 2013, 24,
1423-1427.
The N-arylation of aromatic and aliphatic secondary acyclic amides as
poor nucleophiles has been accomplished using a simple and cheap copper
catalytic system. The corresponding tertiary acyclic amides have been obtained
in good to excellent yields.
E. Racine, F. Monnier, J.-P. Vors, M. Taillefer, Org. Lett., 2011,
13, 2818-2821.
Microwave-assisted, palladium-catalyzed C-N bond-forming reactions with aryl/heteroaryl
nonaflates and amines using soluble amine bases resulted in good to
excellent yields of arylamines in short reaction times.
R. E Tundel, K. W. Anderson, S. L. Buchwald, J. Org. Chem.,
2006,
71, 430-433.
The arylation of N-H and O-H containing compounds at room temperature with
phenylboronic acids is promoted in the presence of cupric acetate and a tertiary
amine. Substrates include phenols, amines, anilines, amides, imides, ureas,
carbamates, and sulfonamides.
D. M. T. Chan, K. L. Monaco, R.-P. Wang, M. P. Winteres, Tetrahedron Lett.,
1998, 39, 2933-2936.
A combination of 1,1,1,3,3,3-hexafluoroispropanol (HFIP) and H2O2
enables a straightforward synthesis of N,N-disubstituted formamides from
imines in
very good yields via an oxidation-rearrangement sequence under smooth reaction
conditions.
N. Llopis, P. Gisbert, A. Baeza, J. Org. Chem., 2020, 85,
11072-11079.
A copper-catalyzed amidation of arylboronic acids with nitriles provides an efficient and complementary methodology for
the synthesis of a broad range of N-arylamides.
H. Huang, Z.-T. Jiang, Y. Wu, C.-Y. Gan, J.-M. Li, S.-K. Xiang, C. Feng, B.-Q.
Wang, W.-T. Yang,
Synlett, 2016, 27, 951-955.
The use of diaryliodonium salts enables mild and metal-free conditions for
arylation of wide scope of secondary acyclic amides. The method allows the
synthesis of tertiary amides with highly congested aryl moieties, and avoids the
regioselectivity problems observed in reactions with (diacetoxyiodo)benzene.
F. Tinnis, E. Stridfeldt, H. Lundberg, H. Adolfsson, B. Olofsson, Org. Lett.,
2015,
17, 2688-2691.
Inexpensive copper(I) iodide catalyzes the formation of N-aryl amides
from arenediazonium salts and primary amides via in situ formation of iodoarenes
in the presence of tetrabutylammonium iodide. This protocol is applicable to
various substituted amides and diazonium salts, giving very good yields of the
desired products.
J. M. Bhojane, V. G. Jadhav, J. M. Nagarkar, Synthesis, 2014, 46,
2951-2956.
A photoinduced transition-metal-free C(aryl)-N bond formation between
2,4,6-tri(aryl)boroxines or arylboronic acids and 1,4,2-dioxazol-5-ones (dioxazolones)
provides N-arylamides under mild conditions. Chloride anions,
either generated in situ by photodissociation of the chlorinated solvent or
added separately as an additive, were found to play a critical cooperative role.
Z. Zhou, J. Kweon, H. Jung, D. Kim, S. Seo, S. Chang, J. Am. Chem. Soc.,
2022, 144, 9161-9174.
A highly efficient Bi(OTf)3-catalyzed multicomponent synthesis of
amidomethylated arenes and heteroarenes from readily available starting
materials proceeds under mild conditions and has a broad substrate scope with
water as the only side product.
A. E. Schneider, G. Manolikakes, Synlett, 2013, 24,
2057-2060.
Brønsted acid catalysis enables a synthesis of secondary amides from ketones
under mild conditions via transoximation and Beckmann rearrangement. In this
reaction, O-protected oximes serve as more stable equivalents of
explosive O-protected hydroxylamines. This method can be used for amide
synthesis from α-branched alkyl aryl ketones. The presence of water is
essential.
K. Hyodo, G. Hasegawa, N. Oishi, K. Kuroda, K. Uchida, J. Org. Chem., 2018, 83,
13080-13087.
The reaction of aromatic compounds with nitroethane in polyphosphoric acid
allows the synthesis of acetamides in good yields. The corresponding amines can
be obtained in situ upon hydrolysis of the acetamides.
A. V. Aksenov, N. A. Aksenov, O. N. Nadein, I. V. Aksenova, Synlett, 2010,
2628-2630.
A planar
chiral indenyl rhodium complex for enantioselective C-H functionalization
catalysis is capable
of catalyzing an asymmetric allylic C-H amidation of unactivated olefins,
delivering a wide range of high-value enantioenriched allylic amide products in
good yields with excellent regio- and enantioselectivity.
C. M. B. Farr, A. M. Kazerouni, B. Park, C. D. Poff, J. Won, K. R. Sharp,
M.-H. Baik, S. B. Blakey, J. Am. Chem. Soc.,
2020, 142, 13996-14004.
Ir(III) catalysis enables an efficient intermolecular branch-selective
allylic C-H amidation in good yields and regioselectivities. The reaction
proceeds through initial allylic C-H activation followed by a subsequent
oxidative amidation with readily available dioxazolones as nitrenoid precursors.
H. Lei, T. Rovis, J. Am. Chem. Soc.,
2019,
141, 2268-2273.
A cobalt-catalyzed allylation of amides with styrenes, in which DMSO was used
as both the solvent and the α-methylene source, provides privileged allylic
amines in high yields, and selectivity for the (E)-isomer of the linear
product.
X. Zhang, Z. Zhou, H. Xu, X. Xu, X. Yu, W. Yi,
Org. Lett., 2019, 21, 7248-7253.
Iridium-catalyzed allylation of potassium trifluoroacetamide or the highly
reactive ammonia equivalent lithium di-tert-butyliminodicarboxylate forms
a range of conveniently protected, primary, α-branched allylic amines in high
yields, high branched-to-linear regioselectivities, and high enantiomeric excess.
M. J. Pouy, A. Leitner, D. J. Weix, S. Ueno, J. F. Hartwig, Org. Lett., 2007,
9, 3949-3952.
A mild and operationally simple hydroamidation of electron-deficient terminal
alkynes by amides in the presence of a Pd-catalyst enables a stereoselective
synthesis of Z-enamides. Hydrogen bonding between the amido proton and
carbonyl oxygen of ester group maybe provides the extra stability to the Z-isomer
of an intermediate vinyl-palladium complex, which subsequently undergoes
protodepalladation and leads to the Z-enamide selectively.
N. Panda, A. K. Jena, J. Org. Chem., 2012,
77, 9407-9412.
Catalysts generated from Pd2(dba)3 and biphenyl ligands efficiently
promote the coupling of amides and carbamates with unactivated vinyl triflates
and tosylates, to provide enamides in good to excellent yields.
M. C. Willis, G. N. Brace, I. P. Holmes,
Synthesis, 2005, 3229-3234.
1,1,1-Tris(hydroxymethyl)ethane as a New, Efficient, and Versatile Tripod
Ligand for Copper-Catalyzed Cross-Coupling Reactions of Aryl Iodides with
Amides, Thiols, and Phenols
Y.-J. Chen, H.-H. Chen, Org. Lett., 2006,
8, 5609-5612.
A versatile and efficient
copper-catalyzed amidation of vinyl bromides and iodides has been developed.
The protocol, which uses a combination of copper iodide and N,N'-dimethyl
ethylenediamine, tolerates substrates bearing ester, silyl ether, and amino
groups.
L. Jiang, G. E. Job, A. Klapars, S. L. Buchwald, Org.
Lett., 2003, 5, 3667-3669.
A Rh(III)-catalyzed umpolung amidation of alkenylboronic acids for the synthesis
of enamides proceeds readily at room temperature and offers a wide functional
group tolerance. In combination with hydroboration, this reaction enables a
formal anti-Markovnikov hydroamidation of terminal alkynes, stereospecifically
affording the trans-enamides in excellent yields.
C. Feng, T.-P. Loh, Org. Lett., 2014,
16, 3444-3447.
A mild, ruthenium-catalyzed anti-Markovnikov addition of secondary amides,
anilides, lactames, ureas, bislactames, and carbamates to terminal alkynes
has been developped. Two complementary protocols provide either the E
or the Z isomers.
L. J. Goossen, J. E. Rauhaus, G. Deng, Angew. Chem. Int. Ed., 2005,
44, 4042-4045.
A catalyst system generated in situ from
bis(2-methallyl)(cycloocta-1,5-diene)ruthenium(II),
1,4-bis(dicyclohexylphosphino)butane, and ytterbium triflate promotes an anti-Markovnikov
addition of primary amides to terminal alkynes under the formation of
Z-configured secondary enamides. An in situ double-bond isomerization reaction
using triethylamine and molecular sieves provides E-isomers.
L. J. Gooßen, M. Blanchot, F. S. M. Salih, K. Gooßen, Synthesis, 2009,
2283-288.
A general and efficient method for the coupling of a wide range of amides with
alkynyl bromides using copper(II) sulfate-pentahydrate and 1,10-phenanthroline
as catalyst leads to a structurally diverse array of ynamides including
macrocyclic ynamides via an intramolecular amidation.
X. Zhang, Y. Zhang, J. Huang, R. P. Hsung, K. C. M. Kurtz, J. Oppenheimer, M. E.
Petersen, I. K. Sagamanova, L. Shen, M. R. Tracey, J. Org. Chem., 2006,
71, 4170-4177.
In copper-catalyzed direct N-alkynylation, the use of pure and anhydrous K3PO4
provides higher ynamide yields in comparison to samples contaminated with
hydrates (K3PO4 · 1.5 H2O and K3PO4
· 7 H2O). With high quality K3PO4, a
number of ynamides were synthesized in good yields. In addition, ynamides can
undergo regioselective hydroamination with carbamates.
K. Dooleweerd, H. Birkedal, T. Ruhland, T. Skrydstrup, J. Org. Chem., 2008,
73, 9447-9450.
A copper-catalyzed direct N-alkynylation of amides has been developed
leading to a facile entry for syntheses of chiral ynamides.
M. O. Frederick, J. A. Mulder, M. R. Tracey, R. P. Hsung, J. Huang, K. C. M.
Kurtz, L. Shen, C. J. Douglas, J. Am. Chem. Soc., 2003,
125, 2368-2369.
A facile route to ynamides in high yields was achieved through an
iron-catalyzed C-N coupling reaction of amides with alkynyl bromides in the
presence of 20 mol % of N,N′-dimethylethane-1,2-diamine (DMEDA).
B. Yao, Z. Liang, T. Niu, Y. Zhang, J. Org. Chem., 2009,
74, 4630-4633.
Stable copper acetylides can be easily activated by oxidation with oxygen in
the presence of simple nitrogen ligands such as TMEDA or imidazole derivatives.
Upon activation, these nucleophilic species undergo a formal umpolung and can
transfer their alkyne subunit to a wide range of heteronucleophiles under
especially mild conditions providing ynamides, ynimines, and alkynylphosphonates
on a multigram scale.
C. Theunissen, M. Lecomte, K. Jouvin, A. Laouiti, C. Guissart, J. Heimburger,
E. Loire, G. Evano, Synthesis, 2014, 46,
1157-1166.
A rhodium-catalyzed N-H and O-H insertion of amides and carboxylic acids
with α-diazo-β-ketoesters gives different α-amido- and
α-carboxylic-β-ketoesters in good yields. The reactions were performed under
mild conditions with 1 mol% of catalyst.
S. Bertelsen, M. Nielsen, S. Bachmann, K. A. Jorgensen,
Synthesis, 2005, 2234-2238.
A range of enol triflates can be coupled with amides, carbamates, and
sulfonamides using palladium catalysis. This method allows the synthesis of
enamides, which may not be readily available by other means.
D. J. Wallace, D. J. Klauber, C.-Y. Chen, R. P.
Volante, Org. Lett., 2003, 5, 4749-4752.
Rhodium(II) azavinyl carbenes, which are conveniently generated from
1-sulfonyl-1,2,3-triazoles, undergo a facile, mild, and convergent formal
1,3-insertion into N-H and O-H bonds of primary and secondary amides, various
alcohols, and carboxylic acids to afford a wide range of vicinally
bisfunctionalized (Z)-olefins with perfect regio- and stereoselectivity.
S. Chuprakov, B. T. Worrell, N. Selander, R. K. Sit, V. V. Fokin, J. Am. Chem. Soc., 2014,
136, 195-202.
Several amides were obtained in high yields by an efficient method from
the corresponding imines which are readily prepared from aldehydes. This
procedure involves the oxidation of aldimines with m-CPBA and BF3·OEt2.
In this reaction, the product is strongly influenced by the electron
releasing capacity of the aromatic substituent (Ar).
G. An, M. Kim, J. Y. Kim, H. Rhee, Tetrahedron Lett., 2003,
44, 2183-2186.
An intramolecular vinylation of various iodoenamides using CuI as the
catalyst and N,N'-dimethylethylenediamine as the ligand led to five-
to seven-membered lactams in moderate to excellent yields.
T. Hu, C. Li, Org. Lett., 2005, 7, 2035-2038.
A convenient and efficient iron-catalyzed aminobromination of alkenes has been
developed using inexpensive FeCl2 as the catalyst,
amides/sulfonamides and NBS as the nitrogen and bromine sources, respectively,
under mild conditions.
Z. Wang, Y. Zhang, H. Fu, Y. Jiang, Y. Zhao, Synlett, 2008,
2667-2668.
Related:
The reaction of N,N-dialkylformamide dimethyl acetal with primary amides
produces N'-acyl-N,N-dialkylformamidines as intermediates. In the
presence of certain Lewis acid additives efficient acyl transfer occurs,
providing new and useful methods for amide exchange such as transamidation.
T. A. Dineen, M. A. Zajac, A. G. Myers, J. Am. Chem. Soc., 2006,
128, 16406-16409.