Categories: C-C Bond Formation > Heteroatom-containing Molecules, Arenes > Trifluoromethylation
Synthesis of trifluoromethyl arenes
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Fluoride ions induce a cross-coupling reaction of organic halides with
trifluoromethyltrialkylsilanes in the presence of Cu(I) salts under mild
reaction conditions to provide the corresponding trifluoromethylated products in
good yields.
M. Oishi, H. Kondo, H. Amii, Chem. Commun., 2009, 86,
1909-1911.
An efficient and broadly applicable copper-catalyzed trifluoromethylation of
aromatic iodides with TMSCF3 was achieved in the presence of borate.
Trimethylborate anchors in situ generated trifluoromethyl anion and suppress its
rapid decomposition.
Z. Gonda, S. Kovács, C. Wéber, T. Gáti, A. Mészáros, A. Kotschy, Z. Novák, Org. Lett.,
2014,
16, 4268-4271.
Fluoride ions induce a cross-coupling reaction of organic halides with
trifluoromethyltrialkylsilanes in the presence of Cu(I) salts under mild
reaction conditions to provide the corresponding trifluoromethylated products in
good yields.
H. Urata, T. Fuchikami, Tetrahedron Lett., 1991,
32, 91-94.
A highly efficient Rh-catalyzed carbenoid addition to trifluoromethylthioether
enables the formation of a trifluoromethyl-substituted sulfonium ylide. This
ylide can act as an electrophilic trifluoromethylation reagent, as demonstrated
by trifluoromethylation of β-ketoesters and aryl iodides.
S. Liu, X. Shao, P. Zhang, L. Lu, Q. Shen, Org. Lett.,
2015,
17, 2752-2755.
Trifluoromethylcopper (“CuCF3”) species can be generated from readily
available phenyl trifluoromethyl sulfoxide. The reagent can be applied in
efficient trifluoromethylations of aryl iodides and activated aryl bromides in
the absence of additional ligands. Furthermore, the “CuCF3” species
can also undergo oxidative cross-coupling with terminal alkynes and arylboronic
acids.
X. Li, J. Zhao, L. Zhang, M. Hu, L. Wang, J. Hu, Org. Lett.,
2015,
17, 298-301.
A mild, copper-catalyzed cross-coupling of Ruppert-Prakash type reagents
(TMSCF3, TMSC2F5, and TMSC3F7)
with aryl and alkyl bromides provides a diverse array of trifluoromethyl,
pentafluoroethyl, and heptafluoropropyl adducts. This light-mediated
transformation enables also the late-stage functionalization of several drug
analogues.
X. Zhao, D. W. C. MacMillan, J. Am. Chem. Soc.,
2020, 142, 19480-19486.
A copper-catalyzed trifluoromethylation of aryl- and alkenylboronic acids with
Togni’s reagent proceeded in good to excellent yields for a range of different
substrates including heteroarylboronic acids and substrates with a variety of
functional groups under mild reaction conditions.
T. Liu, Q. Shen, Org. Lett., 2011,
13, 2342-2345.
A mild and practical protocol for the copper-mediated trifluoromethylation of
aryl and heteroaryl boronic acids using NaSO2CF3
(Langlois’ reagent) and TBHP proceeds at room temperature under ambient
conditions. The products can be readily purified by extraction or column
chromatography.
Y. Ye, S. A. Künzi, M. S. Sanford, Org. Lett., 2012,
14, 4979-7981.
A mild method for the trifluoromethylation of arylboronic acids has been
developed via the merger of photoredox and Cu catalysis with CF3I.
This approach allows trifluoromethylation of electronically diverse aromatic and
heteroaromatic substrates, and tolerates many common functional groups.
Y. Ye, M. S. Sanford, J. Am. Chem. Soc., 2012,
134, 9034-9037.
A mild copper-catalyzed trifluoromethylation of (hetero)arylboronic acid
pinacol esters with YlideFluor provides trifluoromethylated (hetero)arenes in
high yields. The reaction conditions are compatible with a broad range of
functional groups.
J. Liu, Y. Xiao, J. Hao, Q. Shen, Org. Lett., 2023, 25,
1204-1208.
Catalytic trifluoromethylation of aryl- and vinylboronic acids by
2-cyclopropyl-1-(trifluoromethyl)benzo[b]thiophenium proceeded in good yields
for various substrates in the presence of a catalytic amount of CuOAc and
2,4,6-collidine in ethyl acetate under mild reaction conditions at room
temperature.
S. Arimori, N. Shibata, Org. Lett.,
2015,
17, 1632-1635.
Fluoroform-derived CuCF3 exhibits remarkably high reactivity toward
aryl and heteroaryl halides. A broad variety of iodoarenes undergo smooth
trifluoromethylation with the ligandless CuCF3 to give the
corresponding benzotrifluorides in nearly quantitative yield. A number of much
less reactive aromatic bromides also have been trifluoromethylated.
A. Lishchynskyi, M. A. Novikov, E. Martin, E. C. Escudero-Adán, P. Novák, V. V.
Grushin, J. Org. Chem., 2013,
78, 11126-11146.
Difluorocarbene derived from various carbene precursors could be effectively
decomposed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) into a fluoride ion and
carbon monoxide. This decomposition process was successfully combined with a
trifluoromethylation of various (hetero)aryl iodides without the addition of an
external fluoride ion.
J. Zheng, J.-H. Lin, X.-Y. Deng, J.-C. Xiao, Org. Lett.,
2015,
17, 532-535.
A range of benzotrifluorides are conveniently accessible in high yields from
diazonium salts and the inexpensive trifluoromethylating agent TMSCF3
through a copper-mediated Sandmeyer trifluoromethylation reaction. The
combination of diazotization and trifluoromethylation in a one-pot procedure
enables the trifluoromethylation of widely available (hetero)aromatic amines.
G. Danoun, B. Bayermagnai, M. F. Grünberg, C. Matheis, E. Risto, L. J. Gooßen, Synthesis, 2014, 46,
2283-2286.
The well-defined trifluoromethylated argentate nBu4N+[AgI(CF3)2]-
can easily be prepared from fluoroform. The complex is stable in solid state and
in solution under an inert atmosphere. The reaction of (hetero)aryl diazonium
tetrafluoroborates with nBu4N+[AgI(CF3)2]-
provides trifluoromethylated (hetero)arenes in very good yields.
Z. Lu, L. Wang, M. Hughes, S. Smith, Q. Shen, Org. Lett., 2024,
26, 2773-2777.
A mild, copper-promoted Sandmeyer trifluoromethylation of aromatic amines
proceeds smoothly and exhibits good tolerance of many synthetically relevant
functional groups. The reaction provides an alternative approach for the
synthesis of trifluoromethylated arenes and heteroarenes.
J.-J. Dai, C. Fang, B. Xiao, J. Yi, J. Xu, Z.-J. Liu, X. Lu, L. Liu, Y. Fu, J. Am. Chem. Soc., 2013,
135, 8436-8439.
A metal-free, cascade regio- and stereoselective trifluormethyloximation,
cyclization, and elimination strategy of readily available α,β-unsaturated
carbonyl compounds with CF3SO2Na and tBuONO
provides a wide variety of 4-(trifluoromethyl)isoxazoles. Mechanistic studies
revealed a radical pathway for the reaction.
P. Pattanayak, T. Chatterjee, J. Org. Chem., 2023, 88,
5420-5430.
A copper-mediated remarkable domino sequence of cyclization,
trifluoromethylation, and detosylation provides 4-(trifluoromethyl)pyrazoles
from readily accessible α,β-alkynic tosylhydrazones and commercially
available trifluoromethyltrimethylsilane as the CF3 source. The
reaction conditions are mild and convenient with good functional group
compatibility, at room temperature in air.
Q. Wang, L. He, K. K. Li, G. C. Tsui, Org. Lett.,
2017, 19, 658-661.
The use of the well-established fluoroform-derived CuCF3 reagent
enables the synthesis of 2-(trifluoromethyl)indoles from easily
accessible 2-alkynylanilines via a domino
trifluoromethylation/cyclization strategy.
3-formyl-2-(trifluoromethyl)indoles can also be synthesized,
which are useful intermediates for the preparation of trifluoromethylated drug
analogues.
Y. Ye, K. P. S. Cheung, L. He, G. C. Tsui, Org. Lett.,
2018, 20, 1676-1679.
The combination of KMnO4/AcOH mediates a C-H
trifluoromethylation at C-3 of imidazopyridines and C-8 of quinoxalines with
readily available Langlois reagent via a radical pathway. This protocol
showed broad substrate scope and afforded good yields of both
products.
M. E. Firuz, S. Raijai-Daryasarei, F. Rominger, A. Biglari, S. Balalaie, J. Org. Chem., 2023, 88,
10599-10608.