Categories: C-N Bond Formation > Amines >
Synthesis of arylamines
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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.
Anionic N1,N2-diarylbenzene-1,2-diamine
ligands promote the Cu-catalyzed amination of aryl bromides at room temperature.
These ligands were designed to increase the electron density on Cu, thereby
increasing the rate of oxidative addition of aryl bromides, and stabilize the
active anionic CuI complex via a π-interaction.
S.-T. Kim, M. J. Strauss, A. Cabré, S. L. Buchwald, J. Am. Chem. Soc.,
2023, 145, 6966-6975.
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 Ni(II)-bipyridine complex catalyzes an efficient C-N coupling of aryl
chlorides and bromides with various primary and secondary alkyl amines under
direct excitation with light. Intramolecular C-N coupling is also demonstrated.
G. Song, D.-Z. Nong, J.-S. Li, G. Li, W. Zhang, R. Cao, C. Wang, J. Xiao, D.
Xue, J. Org. Chem., 2022, 87,
10285-10297.
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 in situ formed sodium alkoxide cluster, X@RONa catalyzes a mild and
scalable aryl amine synthesis based on aryne chemistry using easily accessible
aryl chlorides as precursors and NaH as a stoichiometric base. The cluster
catalyst features an externally hydrophobic dodecameric sodium alkoxide shell
housing an encapsulated center anion.
J.-L. Yao, Z. Zhang, Z. Li, J. Am. Chem. Soc.,
2024, 146, 8839-8846.
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.
A neutral amination reaction of azides as the nitrogen source with
arylboronic acids in the presence of a rhodium(I) catalyst provides alkyl-aryl
and aryl-aryl secondary amines. The method enables the derivatization of natural
products and pharmaceutical intermediates, and gram-scale reactions were
performed.
S. Xu, H. Guo, Y. Liu, W. Chang, J. Feng, X. He, Z. Zhang, Org. Lett.,
2022, 24, 5546-5551.
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-free electrophilic amination of diarylzinc compounds with readily
accessible O-2,6-dichlorobenzoyl hydroxylamines provides aromatic amines
in the presence of MgCl2 in dioxane at a temperature of 60 °C in 8 to
16 hours.
Y. Li. L. Lv, Y. Wang, Z. Wan, P. Knochel, Y.-H. Chen, Org. Lett., 2024,
26,
503-507.
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.
The use of a CuI/N-carbazolyl-1H-pyrrole-2-carbohydrazide
catalyst system enables a general and efficient N-arylation of
cyclopropylamine with aryl bromides at room temperature. The reaction provides
N-aryl cyclopropylamines in good yields and can be scaled up to produce
the desired products at gram levels.
P. Hong, X. Zhu, X. Lai, Z. Gong, M. Huang, Y. Wan, J. Org. Chem., 2024, 89,
57-62.
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.