Categories: C-N Bond Formation > Amines >
Synthesis of arylamines
A palladium-catalyzed coupling of aryl chlorides with ammonia and gaseous amines as their ammonium salts provides monoarylated products with high selectivity. The resting state for reactions of aryl chlorides is different from the resting state for reactions of aryl bromides, and this change in resting states is proposed to account for a difference in selectivities for reactions of the two haloarenes.
R. A. Green, J. F. Hartwig, Org. Lett., 2014, 16, 4388-4391.
Discovery of N-(Naphthalen-1-yl)-N'-alkyl Oxalamide Ligands Enables Cu-Catalyzed Aryl Amination with High Turnovers
J. Gao, S. Bhunia, K. Wang, L. Gan, S. Xia, D. Ma, Org. Lett., 2017, 19, 2809-2812.
Bis(N-aryl) substituted oxalamides are effective ligands for promoting CuI-catalyzed aryl amination with less reactive (hetero)aryl chlorides at 120 °C with K3PO4 as the base in DMSO to afford a wide range of (hetero)aryl amines in good to excellent yields. Both the electronic nature and the steric property of the aromatic groups of the ligands are important for their efficiency.
W. Zhou, M. Fan, J. Yin, Y. Jiang, D. Ma, J. Am. Chem. Soc., 2015, 137, 11942-11945.
2-aminopyridine 1-oxides are effective ligands for Cu-catalyzed amination of less reactive (hetero)aryl chlorides with aliphatic amines. A wide range of functionalized (hetero)aryl chlorides reacted with various primary and cyclic secondary amines to afford the desired products in good to excellent yields.
W. Liu, J. Xu, X. Chen, F. Zhang, Z. Xu, D. Wang, Y. He, X. Xia, X. Zhang, Y. Liang, Org. Lett., 2020, 22, 7486-7490.
A facile and practical copper powder-catalyzed Ullmann amination of aryl halides with aqueous methylamine and other aliphatic primary amines under organic solvent- and ligand-free condition at 100°C and in air gave N-arylamines as sole products in very good yields. The presence of a small amount of air is essential. Secondary amines and aniline are not reactive. Sensitive substituents are tolerated.
J. Jiao, X.-R. Zhang, N.-H. Chang, J. Wang, J.-F. Wei, X.-Y. Shi, Z.-G. Chen, J. Org. Chem., 2011, 76, 1180-1183.
An organophosphorus-catalyzed C-N bond-forming reductive coupling of nitroalkanes with arylboronic acids and esters shows excellent chemoselectivity for the nitro/boronic acid substrate pair, allowing the synthesis of N-(hetero)arylamines rich in functionalization.
G. Li, Y. Kanda, S. Y. Hong, A. T. Radosevich, J. Am. Chem. Soc., 2022, 144, 8242-8248.
A nickel-catalyzed amination of aryl chlorides with diverse amides via C-N bond cleavage provides a broad range of aromatic amines under mild conditions with excellent functional group tolerance at a low catalyst loading.
J. Li, C. Huang, D. Wen, Q. Zheng, B. Tu, T. Tu, Org. Lett., 2021, 23, 687-691.
A rhodium-catalyzed amination of phenols provides diverse anilines, with water as the sole byproduct. The arenophilic rhodium catalyst facilitates the inherently difficult keto-enol tautomerization of phenols by means of π-coordination, allowing for the subsequent dehydrative condensation with amines.
K. Chen, Q.-K. Kang, Y. Li, W. Giang, Wu, H. Zhu, H. Shi, J. Am. Chem. Soc., 2022, 144, 1144-1151.
The palladium-catalyzed C-N bond formation between dimethylamines and aryl triflates proceeds in excellent yields, using an unsophisticated catalytic system, a mild base, and triflates as electrophiles, which are readily available from inexpensive phenols.
T. Taeufer, J. Pospech, J. Org. Chem., 2020, 85, 7097-7111.
A mild Fe-mediated intermolecular C-H amination of arenes with a highly electrophilic aminating reagent provides unprotected N-methylanilines. An intramolecular variant for the synthesis of tetrahydroquinolines has also been developed. The reactions display a broad functional group tolerance.
E. Falk, V. C. M. Gasser, B. Morandi, Org. Lett., 2021, 23, 1422-1426.
A CuI-based catalytic system in combination with an easily accessible prolinamide ligand enables an Ullmann-type cross coupling of a variety of aromatic, aliphatic amines with aryl halides in aqueous media. The method is mild and tolerates air and a wide range of functional groups. Secondary amines like heteroaromatic amines and nucleobases afford the corresponding coupling products in good to excellent yields too.
G. Chakraborti, S. Paladhi, T. Mandal, J. Dash, J. Org. Chem., 2018, 83, 7347-7359.
An organophosphorus-catalyzed reductive C-N coupling of nitromethane with arylboronic acid derivatives provides N-methylanilines. The small ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) together with phenylsilane as mild terminal reductant mediate the selective installation of the methylamino group.
G. Li, Z. Qin, A. T. Radosevich, J. Am. Chem. Soc., 2020, 142, 16205-16210.
Triphenylphosphine mediates a metal-free, intermolecular, reductive amination between nitroarenes and boronic acids at ambient temperature under visible-light irradiation without any photocatalyst. A wide range of nitroarenes underwent C-N coupling with aryl-/alkylboronic acids providing high yields.
K. Manna, T. Ganguly, S. Baitalik, R. Jana, Org. Lett., 2021, 23, 8634-8639.
A transition-metal-free synthesis of aryl- and heteroarylamines employs a small-ring organophosphorus-based catalyst and a terminal hydrosilane reductant to drive reductive intermolecular coupling of nitroarenes with boronic acids. Applications to the construction of both Csp2-N (from arylboronic acids) and Csp3-N bonds (from alkylboronic acids) are demonstrated; the reaction is stereospecific with respect to Csp3-N bond formation.
T. V. Nykaza, J. C. Cooper, G. Li, N. Mahieu, A. Ramirez, M. R. Luzung, A. T. Radosevich, J. Am. Chem. Soc., 2018, 140, 15200-15205.
A low-valent tungsten complex catalyzes a visible light mediated amination of boronic acids with nitroaromatics at ambient temperature. With readily available W(CO)6 as a precatalyst under external-photosensitizer-free conditions, nitroaromatics smoothly undergo C-N coupling reactions with boronic acids, delivering structurally diverse secondary amines in good yields.
H. Song, Y. Shen, H. Zhou, D. Ding, F. Yang, Y. Wang, C. Xu, X. Cai, J. Org. Chem., 2022, 87, 5303-5314.
An experimentally simple, fast, mild, and scalable transition-metal-free cross-coupling between boronic acids and nitrosoarenes enables the synthesis of di(hetero)arylamines. The procedure tolerates a wide range of functional groups, including carbonyls, nitro, halogens, free OH and NH groups, and also permits the synthesis of sterically hindered compounds.
S. Roscales, A. G. Csák˙, Org. Lett., 2018, 20, 1667-1671.
The use of arynes enables a transition-metal-free approach to a highly monoselective N-arylation of aromatic tertiary amines. The reaction afforded functionalized diaryl amines in good yield. High levels of functional group compatibility and high yields of products are the notable features of the reaction.
S. S. Bhojgude, T. Kaicharla, A. T. Biju, Org. Lett., 2013, 15, 5452-5455.
A transition-metal-free N-arylation of tertiary amines provides trialkylaryl, dialkyldiaryl, and novel triarylalkyl ammonium salts, including N-chiral quaternary ammonium salts. The reaction works at room temperature, open to air with electron-rich or -poor benzyne precursors and different tertiary amines, allowing the synthesis of a broad range of N-aryl ammonium salts that have applications in a variety of fields.
M. Hirsch, S. Dhara, C. E. Diesendruck, Org. Lett., 2016, 18, 980-983.
CuI/DMPAO-Catalyzed N-Arylation of Acyclic Secondary Amines
Y. Zhang, X. Yang, Q. Yao, D. Ma, Org. Lett., 2012, 14, 3056-3059.
A metal-free synthesis of arylamines via the direct amination of phenols using easily accessible aminating reagents provides a versatile route to a broad range of arylamines with various functionalities in good yield. By using a two-step route of amination and oxidative coupling reaction, three naturally occurring carbazole alkaloids are synthesized from commercially available phenols: murrayafoline A, mukonine, and clausenine.
J. Yu, Y. Wang, P. Zhang, J. Wu, Synlett, 2013, 24, 1448-1454.
A cross-coupling of aryl tosylates with amines and anilines was achieved by using a Pd-NHC system based on the popular Pd-PEPPSI precatalyst. The NHC ligand incorporates two dimethylamino groups as backbone substituents for enhancing both the electronic and steric properties of the carbene.
Y. Zhang, G. Lavigne, V. César, J. Org. Chem., 2015, 80, 7666-7673.
A nickel-catalyzed decarboxylation reaction of aryl carbamates forms aromatic amines with carbon dioxide as the only byproduct. As this amination proceeds in the absence of free amines, a range of functionalities, including formyl groups, are compatible.
A. Nishizawa, T. Takahira, K. Yasui, H. Fujimoto, T. Iwai, M. Sawamura, N. Chatani, M. Tobisu, J. Am. Chem. Soc., 2019, 141, 7262-7265.
The combination of PhI(OAc)2 and Cs2CO3 mediates an efficient oxidative 1,2-C to N migration of primary amines. The reaction can be applied to the preparation of both acyclic and cyclic amines. A mechanistic study shows that the rearrangement proceeds via a concerted mechanism.
W. Yamakoshi, M. Arisawa, K. Murai, Org. Lett., 2019, 21, 3023-3027.
In the presence of Pd(OAc)2, PhB(OH)2, and a hindered and electron-rich MOP-type ligand, a variety of primary aryl amines reacted with various aryl tosylates to form the corresponding secondary aryl amines in high yields with high selectivity. Furthermore, the catalyst system was also efficient for the arylation of indoles and hydrazones with aryl tosylates.
X. Xie, G. Ni, F. Ma, L. Ding, S. Xu, Z. Zhang, Synlett, 2011, 955-958.
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.
NiCl2ˇ 6 H2O is an efficient catalyst for the cross-coupling of arylboronic acids with various N-nucleophiles. The method is practical and offers an alternative to the corresponding Cu-mediated Chan-Lam coupling.
D. S. Raghuvanshi, A. K. Gupta, K. N. Singh, Org. Lett., 2012, 14, 4326-4329.
A rhodium-catalyzed amination reaction of aryl halides with amines takes place in the presence of a N-heterocyclic carbene ligand. The active metal species responsible for the reaction progress was identified. This convenient and mild procedure for Rh-catalyzed N-arylation displays a wide range of substrate scope and high degree of functional group tolerance.
M. Kim, S. Chang, Org. Lett., 2010, 12, 1640-1643.
An efficient, transition metal catalyst-free amination of aryl halides under microwave irradiation is a particularly powerful method for the coupling of electron-rich aryl halides with various amines. Meta-substituted anilines have been prepared from ortho- or para-substituted phenylhalides. A mechanism via a benzyne intermediate has been proposed.
L. Shi, M. Wang, C.-A. Fan, F.-M. Zhang, Y.-Q. Tu, Org. Lett., 2003, 5, 3515-3517.
Pd-catalyzed intermolecular aerobic dehydrogenative aromatizations enable the arylation of amines with cyclohexanones and 2-cyclohexen-1-ones. Under optimized reaction conditions, primary and secondary amines are selectively arylated in good yields under an atmosphere of molecular oxygen.
S. A. Girard, X. Hu, T. Knauber, F. Zhou, M.-O. Simon, G.-J. Deng, C.-J. Li, Org. Lett., 2012, 14, 5606-5609.
Amides are excellent N-sources in the NHC-Pd(II)-Im complex catalyzed amination of aryl chlorides. In the presence of KOtBu, various aryl chlorides and amides react smoothly to give the corresponding aminated products in good yields at room temperature within 6 h.
W.-X. Chen, L-X. Shao, J. Org. Chem., 2012, 77, 9236-9239.
The use of arylboroxines and O-benzoyl hydroxylamines as coupling partners enables a transition-metal-free strategy to construct C(sp2)-N bonds. This transformation provides a useful method to access various aromatic amines.
Q. Xiao, L. Tian, R. Tan, Y. Xia, D. Qiu, Y. Zhang, J. Wang, Org. Lett., 2012, 14, 4230-4233.
A catalyst system based on a new biarylmonophosphine ligand shows excellent reactivity for C-N cross-coupling reactions. This catalyst system enables the use of aryl mesylates as a coupling partner and permits a highly selective monoarylation of an array of primary aliphatic amines and anilines at low catalyst loadings and with fast reaction times.
B. P. Fors, D. A. Watson, M. R. Biscoe, S. L. Buchwald, J. Am. Chem. Soc., 2008, 130, 13552-13554.
A silane-promoted nickel-catalyzed amination of aryl chlorides with a catalytic amount of Ni(acac)2 and 3,5,6,8-tetrabromo-1,10-phenanthroline as ligand in the presence of polymethylhydrosiloxane gives the desired (het)arylamines in good yields. The reaction is sensitive to the nature and amount of the silane promoter.
G. Manolikakes, A. Gavryushin, P. Knochel, J. Org. Chem., 2008, 73, 1429-1434.
Air- and moisture-stable Ni(II)-(σ-aryl) complexes, associated with N-heterocyclic carbene ligands, produce a catalytically active Ni(0) species in situ for an efficient amination of aryl chlorides with anilines and secondary cyclic amines under mild conditions.
C. Chen, L-M. Yang, J. Org. Chem., 2007, 72, 6324-6327.
Aryl triflates substituted with both electron-poor and electron-rich groups are effectively converted to the corresponding anilines under microwave irradiation in 1-methyl-2-pyridone (NMP) without base and catalyst. It is noteworthy that halogenated aryl triflates chemoselectively afford halogenated anilines.
G. Xu, Y.-G. Wang, Org. Lett., 2004, 6, 985-987.
A nickel complex derived from dppf, along with NaOt-Bu as the base, enabled challenging aminations of aryl sulfamates. Palladium-catalyzed aminations of imidazolylsulfonates with rac-BINAP as the ligand offer an improved functional group tolerance.
L. Ackermann, R. Sandmann, W. Song, Org. Lett., 2011, 13, 1784-1786.
N-Arylation of azoles and amines with arylboronic acids was efficiently carried out with heterogeneous copper(I) oxide in methanol at room temperature under base-free conditions. Various arylboronic acids and amines were converted to the corresponding N-arylazoles and N-arylamines in very good yields, demonstrating the versatility of the reaction.
B. Sreedhar, G. T. Venkanna, K. B. S. Kumar, V. Balasubrahmanyam, Synthesis, 2008, 795-799.
Microwave-assisted conditions enabled a simple, rapid, one-pot synthesis of arylaminomethyl acetylenes in very good yields using arylboronic acids, aqueous ammonia, propargyl halides, copper(I) oxide and water as the solvent within ten minutes.
Y. Jiang, S. Huang, Synlett, 2014, 25, 407-410.
The reaction of di-tert-butyl dicarbonate or a chloroformate and sodium azide with an aromatic carboxylic acid produces the corresponding acyl azide. The acyl azide undergoes a Curtius rearrangement to form an isocyanate derivative which is trapped either by an alkoxide or by an amine to form the aromatic carbamate or urea.
H. Lebel, O. Leogane, Org. Lett., 2006, 8, 5717-5720.
Palladium/N-heterocyclic carbene (NHC) catalysis achieves an amination of diaryl sulfoxides with anilines and alkylamines. This amination tolerates a wide range of functional groups such as silyl, boryl, methylsulfanyl, and halogen moieties. Regioselective amination of unsymmetrical diaryl sulfoxides was also executed by means of steric bias.
Y. Yoshida, S. Otsuka, K. Nogi, H. Yorimitsu, Org. Lett., 2018, 20, 1134-1137.
β-Amino acids have an accelerating effect for the Ullmann-type aryl amination reaction: CuI-catalyzed coupling reactions of aryl halides with β-amino acids or β-amino esters are completed at 100°C in 48 h. This coupling reaction can be used to prepare enantiopure N-aryl β-amino acids. An efficient synthesis of SB-214857, a potent GPIIb/IIIa receptor antagonist, is described.
D. Ma, C. Xia, Org. Lett., 2001, 3, 2583-2586.
An efficient, mild and transition-metal-free N-arylation of amines, sulfonamides, and carbamates and O-arylation of phenols and carboxylic acids has been achieved by using various o-silylaryl triflates in the presence of CsF.
Z. Liu, R. C. Larock, J. Org. Chem., 2006, 71, 3198-3209.
Iridium-catalyzed direct ortho C-H amidation of arenes works well with sulfonyl- and aryl azides as the nitrogen source. The reaction proceeds efficiently with a broad range of conventional directing groups with excellent functional group compatibility under mild conditions via 5- as well as 6-membered iridacycle intermediates.
D. Lee, Y. Kim, S. Chan, J. Org. Chem., 2013, 78, 11102-11109.
Attractive noncovalent interactions between a sulfamate-protected aniline as anionic substrate and an incoming radical cation is able to guide the latter to the arene ortho position. Subsequent cleavage of the sulfamate group leads directly to ortho-phenylenediamines, key building blocks for a range of medicinally relevant diazoles. This method can deliver both free amines and monoalkyl amines.
J. E. Gillespie, C. Morrill, R. J. Phipps, J. Am. Chem. Soc., 2021, 143, 9355-9360.
A copper-catalyzed electrophilic amination of simple and functionalized aryl, heteroaryl-, benzyl, n-alkyl, sec-alkyl, and tert-alkyl diorganozinc nucleophiles with R2NOC(O)Ph and RHNOC(O)Ph reagents as electrophilic nitrogen sources provides tertiary and secondary amines, respectively, in generally good yields. In many cases, the product may be isolated analytically pure after a simple extractive workup. A Cu-catalyzed amination of Grignard reagents using cocatalysis by ZnCl2 is described.
A. M. Berman, J. S. Johnson, J. Org. Chem., 2006, 71, 219-224.
The NiCl2(PPh3)2-PPh3-catalyzed cross-coupling of bromomagnesium diarylamides, generated in situ from diarylamines, with aryl bromides or iodides is an inexpensive, convenient, and practical method for the synthesis of triarylamines.
C. Chen, L.-M. Yang, Org. Lett., 2005, 7, 2209-2211.
The reaction of an imine with an aryne generated in situ in the presence of a dialkyl phosphite provides α-aminophosphonates in good yields. This transition-metal-free multicomponent phosphonylation shows a broad substrate scope.
T. Lim, B. M. Kim, J. Org. Chem., 2020, 85, 13037-13049.
CuCl catalyzes a highly efficient electrophilic amination reaction of readily available heteroarenes with O-benzoyl hydroxylamines via a one-pot C-H alumination to afford various heteroaryl amines in very good yields. The reaction can be performed in a single vessel on gram scales.
H. Yoon, Y. Lee, J. Org. Chem., 2015, 80, 10244-10251.
A facile metal-free oxidative amination of benzoxazole by activation of C-H bonds with secondary or primary amines in the presence of catalytic iodine in aqueous tert-butyl hydroperoxide proceeds smoothly at ambient temperature under neat reaction condition to furnish products in high yields. This user-friendly method produces only tertiary butanol and water as byproducts.
M. Lamani, K. R. Prabhu, J. Org. Chem., 2011, 76, 7938-7944.