Categories: C-N Bond Formation >
Synthesis of amides
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.
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.
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.
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.
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.
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.