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Benzylation, synthesis of diarylmethanes and diarylalkanes
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KN(SiMe3)2 in combination with a (NIXANTPHOS)Pd
catalyst accomplished a deprotonative activation of toluene derivatives to
permit cross-coupling with aryl bromides. Good to excellent yields are obtained
with a range of electron-rich to neutral aryl bromides. Both electron-rich and
electron-poor toluene derivatives are well tolerated.
S.-C. Sha, S. Tcyrulnikov, M. Li, B. Hu, Y. Fu, M. C. Kozlowski, P. J. Walsh, J. Am. Chem. Soc.,
2018,
140, 12415-12423.
A fully heterogeneous metallaphotocatalytic C-C cross-coupling of aryl/vinyl
halides with alkyl/allyltrifluoroborates is mediated by bipyridyl-Ni(II)-carbon nitride as a stable and recyclable
bifunctional catalyst. This visible-light-mediated heterogeneous protocol
enables a sustainable synthesis of diverse valuable diarylmethanes and allylarenes
in high efficiency.
X. Dan, Q. Yang, L. Xing, Y. Tang, W. Wang, Y. Cai, Org. Lett., 2023, 25,
4124-4129.
A metal-free carbon-carbon bond-forming coupling between tosylhydrazones and
boronic acids is very general and functional-group tolerant. As the required
tosylhydrazones are easily generated from carbonyl compounds, it can be seen as
a reductive coupling of carbonyls, a process of high synthetic relevance that
requires several steps using other methodologies.
J. Barluenga, M. Tomás-Gamasa, F. Aznar, C. Valdés, Nat. Chem., 2009,
1, 494-499.
J. Barluenga, M. Tomás-Gamasa, F. Aznar, C. Valdés, Nat. Chem., 2009,
1, 494-499.
The presence of catalytic amounts of 3-methyl-1-sulfonic acid imidazolium
tetrachloroaluminate ([Msim]AlCl4) or silica sulfuric acid (SSA) enables
an
efficient benzylation of a range of aromatic compounds by benzyl
acetate under mild conditions. Simple methodology, easy workup procedure, clean
reaction and reusability of the catalyst are some advantages.
M. A. Zolfigol, H. Vahedi, S. Azimi, A. R. Moosavi-Zare, Synlett, 2013, 24,
1113-1116.
A highly efficient secondary benzylation procedure of nucleophiles (arenes,
heteroarenes, alcohols, thiols, amides) with benzylic alcohols afforded the corresponding benzylated
products in moderate to excellent yields in the presence of a high-valent heterobimetallic complex [Ir2(COD)2(SnCl3)2(Cl)2(μ-Cl)2] as the catalyst.
S. Podder, J. Choudhury, S. Roy, J. Org. Chem., 2007,
72, 3129-3132.
A nickel-catalyzed cross-electrophile coupling reaction between benzyl
alcohols and aryl halides is mediated by a low-valent titanium reagent generated
from TiCl4(2,6-lutidine) and manganese powder. The reaction afforded the
cross-coupled product in high yield.
T. Suga, Y. Ukaji, Org. Lett.,
2018, 20, 7846-7850.
The combination of anodic preparation of alkoxy triphenylphosphonium ion and
nickel-catalyzed cathodic reductive cross-coupling enables an efficient method
to construct C(sp2)-C(sp3) bonds, in which free alcohols
and aryl bromides can be directly used as coupling partners.
Z. Li, W. Sun, X. Wang, L. Li, Y. Zhang, C. Li, J. Am. Chem. Soc.,
2021, 143, 3586-3543.
The combination of inexpensive cerium and nickel catalysts enables the use of
easily accessible free alcohols as operationally simple and robust carbon
pronucleophiles in selective C(sp3)-C(sp2) cross-couplings
with the extrusion of formaldehyde. A broad range of free alcohols and aromatic
halides can be employed in this transformation.
Y. Chen, X. Wang, X. He, Q. An, Z. Zuo, J. Am. Chem. Soc.,
2021, 143, 4896-4902.
Easily reachable electron-poor/rich primary and secondary benzylic phosphates
are suitably substrates for Friedel-Crafts benzylation reactions with only 1.2
equiv activated/deactivated arenes without additional solvent to access
structurally and electronically diverse triarylmethanes, diarylethanes, and
diarylmethanes with excellent yields and selectivities at room temperature
within short reaction times.
G. Pallikonda, M. Chakravarty, J. Org. Chem.,
2016,
81, 2135-2142.
An efficient Pd-catalyzed coupling of benzylic phosphates with arylsilanes
provides straightforward access to diarylmethanes in very good yields. The
reaction tolerates a wide range of functionalities such as halide, alkoxyl, and
nitro groups.
P. Zhang, J. Xu, Y. Gao, X. Li, G. Tang, Y. Zhao,
Synlett, 2014, 25, 2928-2932.
The use of 1,3-dicyclohexylimidazol-2-ylidene as a ligand enables a
nickel-catalyzed cross-coupling of methoxyarenes with alkyl Grignard reagents
via cleavage of the C(aryl)-OMe bond. Various alkyl groups, including Me, Me3SiCH2,
ArCH2, adamantyl, and cyclopropyl can be introduced.
M. Tobisu, T. Takahira, N. Chatani, Org. Lett.,
2015,
17, 4352-4355.
Post-oxidative addition precatalysts (POxAPs) are very efficient in catalyzing
Negishi reactions between organohalides and organozinc reagents. Using very low
catalyst loadings, POxAPs show similar catalytic activities to those of
classical precatalysts such as PEPPSI-IPr or XPhos Pd G4. POxAPs are easily
prepared, stable to air and moisture, and tolerate a wide range of functional
groups.
S.-Q. Tang, M. Schmitt, F. Bihel, Synthesis, 2020, 52,
51-59.
Bu4NI as additive accelerates the palladium(0)-catalyzed
cross-coupling between benzylic zinc bromides and aryl or alkenyl triflates.
Remarkably, it further enables a new nickel(0)-catalyzed cross-coupling between
functionalized benzylic zinc reagents and primary alkyl iodides under mild reaction conditions.
M. Piber, A. E. Jensen, M. Rottländer, P. Knochel,
Org. Lett., 1999, 1, 1323-1326.
The use of Ni(cod)2 in conjunction with
1,3-dicyclohexylimidazol-2-ylidene enables a cross-coupling of aryl and benzyl
methyl ethers with organoboron reagents. This method not only allows for the use
of readily available methyl ethers as halide surrogates but also provides a
functional group tolerant method for the late-stage derivatization of complex
molecules.
M. Tobisu, A. Yasutome, H. Kinuta, K. Nakamura, N. Chatani, Org. Lett.,
2014,
16, 5572-5575.
A nickel-catalyzed cross coupling of benzylic ammonium triflates with aryl
boronic acids affords diarylmethanes and diarylethanes. This reaction proceeds
under mild reaction conditions and with exceptional functional group tolerance.
Further, it transforms branched benzylic ammonium salts with excellent chirality
transfer, offering a new strategy for the synthesis of highly enantioenriched
diarylethanes.
P. Maity, D. M. Shacklady-McAtee, G. P. A. Yap, E. R. Sirianni, M. P. Watson, J. Am. Chem. Soc., 2013,
135, 280-285.
A palladium-catalyzed coupling of N,N-ditosylbenzylamines with
arylboronic acids results in diarylmethanes in high yields. The N,N-ditosylimide
group provided an efficient leaving group for the Pd-catalyzed benzylation of
arylboronic acids.
S. Yoon, M. C. Hong, H. Rhee, J. Org. Chem., 2014,
79, 4206-4207.
A magnesium-mediated reductive cross-coupling between benzyl chlorides and aryl
chlorides or fluorides gives diarylmethanes in good to excellent yields in a
one-pot manner using easy-to-access mixed PPh3/NHC Ni(II) complexes
of Ni(PPh3)(NHC)Br2 as catalyst precursors.
J. Zhang, G. Lu, J. Xu, H. Sun, Q. Shen, Org. Lett.,
2016, 18, 2860-2863.
The reaction of benzylic chlorides with Al-powder in the presence of InCl3
as catalyst provides various functionalized benzylic aluminum
sesquichlorides under mild conditions. These organometallics reacted smoothly in
Pd-catalyzed cross-couplings, or Cu-mediated acylations, allylations, or
1,4-addition reactions. Substrates prone to Wurtz coupling can be converted to
benzylic zinc compounds first.
T. D. Blümke, K. Gross, K. Karaghiosoff, P. Knochel, Org. Lett., 2011,
13, 6440-6443.
Diarylmethanes can be accessed efficiently by Suzuki-Miyaura cross-couplings of
arylboronic acids with benzyl halides mediated by trans-PdBr(N-Succ)(PPh3)2.
The methodology can be applied to the synthesis of heteroaryl analogues.
I. J. S. Fairlamb, P. Schnal, R. J. K. Taylor, Synthesis, 2009,
508-510.
The palladium-catalyzed cross-coupling of various benzylic carbonates with
arylboronic acids gave the corresponding diarylmethanes in high yields. The
catalyst is generated in situ from [Pd(η3-C3H5)Cl]2
and 1,5-bis(diphenylphosphino)pentane (dpppe).
R. Kuwano, M. Yokogi, Org. Lett., 2005,
7, 945-947.
A cross-coupling reaction of various aryl, heteroaryl, and benzyl chlorides with
ArMgX is catalyzed by nickel in the presence of a bidentate phosphine ligand.
The ligand is stable in air and forms a stable complex in situ upon reaction
with Ni(CH3CN)2Cl2.
R. Ghosh, A. Sarkar, J. Org. Chem., 2010,
75, 8283-8386.
A Ni-catalyzed regioselective alkylarylation of vinylarenes with alkyl halides
and arylzinc reagents provides 1,1-diarylalkanes. The reaction proceeds
well with primary, secondary and tertiary alkyl halides, and electronically
diverse arylzinc reagents.
S. KC, R. K. Dhungana, B. Shrestha, S. Thapa, N. Khanal, P. Basnet, R. W. Lebrun,
R. Giri, J. Am. Chem. Soc.,
2018,
140, 9801-9805.
A visible-light-driven nickel and iridium dual catalysis enables the migratory
benzylic arylation of nonactivated alkyl bromides with aryl bromides to provide
1,1-diarylalkanes in the presence of diisopropylamine as the terminal reductant.
This method tolerates a wide range of functional groups.
L. Peng, Z. Li, G. Yin, Org. Lett.,
2018, 20, 1880-1883.
A ligand-controlled nickel migration/arylation enables a highly efficient remote
reductive cross-electrophile coupling. This general protocol allows the use of
abundant and bench-stable alkyl bromides and aryl bromides for the synthesis of
a wide range of structurally diverse 1,1-diarylalkanes in excellent yields and
high regioselectivities under mild conditions.
F. Chen, K. Chen, Y. Zhang, Y. He, Y.-M. Wang, S. Zhu, J. Am. Chem. Soc., 2017,
139, 13929-13935.
Judicious choice of ligand for both copper(I) hydride and palladium catalysis
enabled a hydroarylation protocol to work for an extensive array of aryl
bromides and styrenes, including β-substituted vinylarenes and six-membered
heterocycles, under relatively mild conditions.
S. D. Friis, M. T. Pirnot, S. L. Buchwald, J. Am. Chem. Soc., 2016,
138, 8372-8375.
The use of a simple stilbene ligand enables a stereospecific Suzuki-Miyaura
cross-coupling of chiral tertiary benzylic carboxylates to provide challenging
all-carbon diaryl quaternary stereocenters in good yield and ee. Precedent reaction systems required substrates
substituted with naphthyl groups or specific heteroaryls to obtain high yields and stereochemical fidelities.
J. Xu, O. P. Bercher, M. P. Watson, J. Am. Chem. Soc.,
2021, 143, 8608-8613.
The use of the Xantphos ligand in a mild palladium-catalyzed Kumada-Corriu
reaction of secondary benzylic bromides with aryl and alkenyl Grignard reagents
minimizes the undesired β-elimination pathway. The corresponding cross-coupling
products can be isolated in good yields with inversion of the configuration.
A. López-Pérez, J. Adrio, J. C. Carretero, Org. Lett., 2009,
11, 5514-5517.
An efficient Hiyama coupling reaction between benzylic halides and
aryltrialkoxysilanes using Pd nanoparticles allows the synthesis of a diverse
range of diarylmethanes which are ubiquitous units of natural products and
pharmaceuticals.
D. Srimani, A. Bej, A. Sarkar, J. Org. Chem., 2010,
75, 4296-4299.
Suzuki-Miyaura cross-coupling of benzylic phosphates with arylboronic acids
using a simple catalytic system of palladium(II) acetate and
triphenylphosphine with either potassium phosphate or potassium carbonate as
the base and toluene as the solvent at 90°C allows the preparation of a
series of structurally diverse diarylmethanes.
M. McLaughlin, Org. Lett.,
2005,
7, 4875-4878.
Coupling of sterically hindered aryl and activated alkyl chlorides bearing
β-hydrogens has been successfully achieved by using N-heterocyclic
carbene (NHC)Pd-carboxylate complexes as catalysts.
R. Singh, M. S. Viciu, N. Kramareva, O. Navarro, S. P. Nolan, Org. Lett.,
2005,
7, 1829-1832.
A new, reusable Pd/MgLa mixed oxide catalyst has been applied successfully
in the Suzuki-Miyaura cross-coupling reaction of aryl halides as well as
benzylic bromide with boronic acids in ethanol. The catalyst is air stable,
can be stored and handled under an ambient atmosphere and after the reaction
it can be recovered by simple filtration and reused without significant loss
of activity.
A. Cwik, Z. Hell, F. Figueras, Org. Biomol. Chem., 2005,
3, 4307-4309.
Palladium catalyzed Suzuki-Miyaura coupling with aryl chlorides using a
bulky phenanthryl N-heterocyclic carbene ligand
C. Song, Y. Ma, Q. Chai, C. Ma, W. Jiang, M. B. Andrus, Tetrahedron, 2005,
61, 7438-7446.
A combination of copper chloride, triethyl phosphite, and tetrabutylammonium
iodide is a very efficient catalytic system for cross-coupling reaction of
arylmagnesium halides with benzylic phosphates.
C. C. Kofink, P. Knochel, Org. Lett.,
2006,
8, 4121-4124.
A hybrid catalyst of iron oxide nanoparticles on carboxy-functionalized graphite
demonstrated superior catalytic activity towards the alkylation of arenes with
alkyl halides in contrast to commercial graphite or unsupported iron oxide
nanoparticles. The catalyst can be reused up to five times with a minimal loss
of catalytic activity.
V. Rajpara, S. Banerjee, G. Sereda, Synthesis, 2010,
2835-2840.
A novel InCl3/SiO2-catalyzed hydroarylation of various
styrenes with arenes can be carried out under solvent-free conditions to afford
a series of 1,1-diarylalkanes in high yields and with good regioselectivities.
The catalyst can be reused six times without obvious loss of catalytic activity.
G. Sun, H. Sun, Z. Wang, M.-M. Zhou, Synlett, 2008, 1096-1100.
A high-yielding, and scalable deprotonative-cross-coupling process (DCCP) for
palladium-catalyzed C(sp3)-H arylation of simple diarylmethane
derivatives with aryl bromides can be conducted at room temperature. This method
facilitates access to a variety of sterically and electronically diverse hetero-
and nonheteroaryl-containing triarylmethanes, a class of compounds with various
applications and interesting biological activity.
J. Zhang, A. Bellomo, A. D. Creamer, S. D. Dreher, P. J. Walsh, J. Am. Chem. Soc., 2012,
134, 13765-13772.
Palladium-catalyzed reductive coupling reactions between N-tosylhydrazones
and aryl halides provide a general route for the synthesis of triarylmethanes.
Y. Xia, F. Hu, Z. Liu, P. Qu, R. Ge, C. Ma, Y. Zhang, J. Wang, Org. Lett., 2013,
15, 1784-1787.
Suzuki-Miyaura coupling of diarylmethyl carbonates with arylboronic acids gives
various triarylmethanes in the presence of [Pd(η3-C3H5)Cl]2−DPPPent
(1,5-bis(diphenylphosphino)pentane) as catalyst.
J.-Y. Yu, R. Kuwano, Org. Lett., 2008,
10, 973-976.
An efficient palladium-catalyzed Suzuki coupling of
1,1-diarylmethyl-trimethylammonium triflates with arylboronic acids provides triarylmethane derivatives in
very good yields. The reaction offeres broad substrate scope and tolerates reactive functional groups such as vinyl and formyl groups.
Z. Zhang, H. Wang, N. Qiu, Y. Kong, W. Zeng, Y. Zhang, J. Zhao, J. Org. Chem., 2018, 83,
8710-8715.
A chiral sulfinamide phosphine ligand enables a Pd-catalyzed enantioselective
three-component coupling of N-tosylhydrazones, aryl halides, and terminal
alkynes under mild conditions utilizing (GF-Phos) to provide chiral
diarylmethyl alkynes. This reaction features readily available starting
materials, general substrate scope, high enantioselectivity, and ease of
scale-up.
G. Zhao, Y. Wu, H.-H. Wu, J. Yang, J. Zhang, J. Am. Chem. Soc.,
2021, 143, 17983-17988.
A cobalt complex catalyzes an asymmetric cross-coupling of
α-bromo-α-fluorotoluene derivatives with a variety of aryl zincates derived from
lithium aryl n-butyl pinacol boronates and ZnBr2 under mild
reaction conditions. The reaction tolerates various common functional groups
such as fluoride, chloride, bromide, cyano, or ester groups.
W. Huang, X. Wan, Q. Shen,
Org. Lett., 2020, 22, 4327-4332.
Arylboration of vinylarenes and methyl crotonate with aryl halides and
bis(pinacolato)diboron by cooperative Pd/Cu catalysis gives
2-boryl-1,1-diarylethanes and α-aryl-β-boryl ester in a regioselective manner.
The reaction is compatible with various functionalities and can be scaled-up to
a gram scale.
K. Semba, Y. Nakao, J. Am. Chem. Soc., 2014,
136, 7567-7570.
A nickel-catalyzed 1,2-arylboration of vinylarenes with aryl halides provides
various 2-boryl-1,1-diarylalkanes, which constitute a class of significant
pharmacophores, in the presence of bis(pinacolato)diboron under mild reaction
conditions. This three-component cascade reaction exhibits good functional
group tolerance and excellent chemo- and stereoselectivity.
W. Wang, C. Ding, H. Pang, G. Yin,
Org. Lett., 2019, 21, 3968-3971.
Sm(OTf)3 is an effective catalysts for a versatile and efficient
halogen-promoted highly regio- and stereoselective Friedel-Crafts (F-C)
alkylation of electron-rich arenes with alkenes and α,β-unsaturated carbonyl
compounds in the presence of NBS or I2 as halogen sources.
S. Haira, B. Maji, S. Bar, Org. Lett., 2007,
9, 2783-2786.
A nickel-catalyzed enantioselective cross-coupling
reaction of aryl titanates with α-CF3-benzyl bromides enables the synthesis of chiral α-CF3-substituted benzhydryls in good yields and excellent enantioselectivities.
The use of commercially available anesthetic halothane as a cheap fluorinated
building block in a sequential one-pot reaction with two different aryl
titanates is also described.
A. Varenikov, E. Shapiro, M. Gandelman, Org. Lett., 2020, 22, 9386-9391.
The superacid-catalyzed reaction of various olefinic amines and
related compounds with benzene gives addition products in good yields. The
formation of reactive, dicationic electrophiles is proposed.
Y. Zhang, A. McElrea, G. V. Sanchez, Jr., D. Do, A. Gomez, S. L . Aguirre, R. Rendy, D. A. Klumpp, J. Org. Chem., 2003,
68, 5119-5122.
The reaction of different functionalised organolithium compounds prepared by
DTBB-catalysed lithiation of isochromane, phthalane, 2,3-dihydrobenzofuran
and 1-chloro-3,3-diethoxypropane with an equimolecular amount of zinc
bromide, followed by reaction with an aryl or an alkenyl bromide in the
presence of a palladium catalyst gives the expected cross-coupling products.
M. Yus, J. Gomis, Eur. J. Org. Chem., 2002, 1989-1995.
A palladium-catalyzed cross-coupling reaction between acetates of
Baylis-Hillman adducts and organosilanes in PEG as solvent is described.
G. W. Kabalka, J. Org. Chem., 2005,
70, 9207-9210.