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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.