Ni(II)/Al(0) mediated benzylic \(\hbox {Csp}^{3}\)-\(\hbox {Csp}^{3}\) coupling in aqueous media

  • Mukesh Kumar Nayak
  • Priyabrata Mukhi
  • Anuradha Mohanty
  • Sohel Samim Rana
  • Rajat Arora
  • Himani Narjinari
  • Sujit RoyEmail author
Regular Article



The reaction of benzyl bromides and chlorides with aluminium metal powder or foil (1.2 eqv.) in the presence of catalytic nickel nitrate (10 mol%) in water at room temperature resulted in homocoupling to the corresponding bibenzyl products which were isolated in moderate to good yields. In sharp contrast, the same reaction in organic solvents like dichloromethane, dimethylformamide, acetonitrile, methanol and toluene yielded only a trace amount of the desired product. The scope of the reaction was tested with substituents on the aromatic ring such as Me-, Cl-, CN-, F-, \(\hbox {NO}_{2}\)-, Ph- as well as \(2{^{\circ }}\) benzyl halides.

Graphical abstract

The reagent combination of aluminium metal and catalytic \(\hbox {Ni}(\hbox {NO}_{3})_{2}\) promotes the homocoupling of benzyl bromides and chlorides giving rise to the corresponding bibenzyl products in good to excellent yields. The reaction is greatly facilitated in water and showed good functional group tolerance. Besides the mild reaction condition and bench-friendliness, the present reaction constitutes the first example of aluminium-mediated homocoupling of a halide in water.


C-C bond formation reaction in water aluminium nickel benzyl halide 



The authors thank the Institute for support including fellowship.

Supplementary material

12039_2019_1638_MOESM1_ESM.pdf (733 kb)
Supplementary material 1 (pdf 733 KB)


  1. 1.
    (a) Johansson Seechurn C C C, Kitching M O, Colacot T J and Snieckus V 2012 Palladium catalysed cross-coupling Angew. Chem. Int. Ed. 51 5062; (b) Molander G A and Canturk B 2009 Organotrifluoroborates and monocoordinated palladium complexes as catalysts–A perfect combination for suzuki–miyaura coupling Angew. Chem. Int. Ed. 48 9240; (c) Mesganaw T and Garg N K 2013 Ni and Fe Catalyzed cross-coupling reactions of phenol derivatives Org. Process Res. Dev. 17 29; (d) Li H, Johansson Seechurn C C C and Colacot T J 2012 Development of preformed Pd catalysts for cross-coupling reactions ACS Catal. 2 1147; (e) Wu X-F, Anbarasan P, Neumann H and Beller M 2010 Palladium-catalyzed coupling reactions as key methods in organic synthesis Angew. Chem. Int. Ed. 49 9047; (f) Wang Z-X and Liu N 2012 Nickel catalysed cross-coupling with pincer ligands Eur. J. Inorg. Chem. 901; (g) Grzybowski M, Skonieczny K, Butenschçn H and Gryko D T 2013 Comparison of oxidative aromatic coupling and the scholl reaction Angew. Chem. Int. Ed. 52 9900Google Scholar
  2. 2.
    (a) Yuan Y and Bian Y 2008 Efficient homocoupling reactions of halide compounds catalyzed by manganese (II) chloride Appl. Organometal. Chem. 22 15; (b) Yamamoto T 2014 Homocoupling of aryl halides promoted by an \(\text{NiCl}_{2}\)/bpy/Mg system in DMF Appl. Organometal. Chem. 28 598; (c) Chen S-Y, Zhang J, Li Y-H, Wen J, Bian S-Q and Yu X-Q 2009 Cobalt-catalyzed homo-coupling of aryl and alkenyl bromide using atmospheric oxygen as oxidant Tetrahedron Lett. 50 6795; (d) Ogawa H, Yang Z-K, Minami H, Kojima K, Saito T, Wang C and Uchiyama M 2017 Revisitation of organoaluminum reagents affords a versatile protocol for C-X (\(\text{ X } = \text{ N }\), O, F) bond-cleavage cross-coupling ACS Catal. 7 3988; (e) Cahiez G, Moyeux A, Buendia J and Duplais C 2007 Manganese- or Iron-catalyzed homocoupling of Grignard reagents using atmospheric oxygen as an oxidant J. Am. Chem. Soc. 129 13788; (f) Biradar D B and Gau H-M 2011 Simple and efficient nickel-catalyzed cross-coupling reaction of alkynylalanes with benzylic and aryl bromides Chem. Commun. 47 10467; (g) Lv L, Qiu Z, Li J, Liu M and Li C-J 2018 N\(_{2}\)H\(_{4}\) as traceless mediator for homo- and crossaryl coupling Nat. Commun. 9 4739Google Scholar
  3. 3.
    (a) Rudolph A and Lautens M 2009 Secondary alkyl halides in transition-metal catalyzed cross-coupling reactions Angew. Chem. Int. Ed. 48 2656; (b) Jana R, Pathak T P and Sigman M S 2011 Advances in transition metal (Pd,Ni,Fe) catalyzed cross-coupling reactions using alkyl-organometallics as reaction partners Chem. Rev. 111 1417; (c) Frisch A C and Beller M 2005 catalysts for cross-coupling reactions with non-activated alkyl halides Angew. Chem. Int. Ed. 44 674; (d) Huther N, McGrail P T and Parsons A F 2002 Biphasic manganese carbonyl reactions: a new approach to making carbon–carbon bonds Tetrahedron Lett. 43 2535; (e) Barrero A F, Herrador M M, Moral J F Q L D, Arteaga P, Akssira M, Hanbali F E, Arteaga J F, Die’guez H R and Sa’nchez E M 2007 Couplings of benzylic halides mediated by titanocene chloride: synthesis of bibenzyl derivative J. Org. Chem. 72 2251Google Scholar
  4. 4.
    (a) Cirla A and Mann J 2003 Combretastatins: from natural products to drug discovery Nat. Prod. Rep. 20 558; (b) Baur J A and Sinclair D A 2006 Therapeutic potential of resveratrol: the in vivo evidence Nat. Rev. Drug Discov. 5 493Google Scholar
  5. 5.
    (a) Wurtz A 1855 Ann. Chim. Phys. 44 275; (b) Wurtz A 1855 Ann. Chem. Pharm. 96 364Google Scholar
  6. 6.
    (a) \(\text{ VCl }_{2}\text{(Py) }_{4}\): Cooper T A 1973 Reductive coupling of aralkyl halides by vanadium(II) J. Am. Chem. Soc. 95 4158; (b) \(\text{ Co }(\text{ PMe }_{3})_{4}\)/Zn: Fallon B J, Corce V, Amatore M, Aubert C, Chemla F, Ferreira F, Luna A P and Pitit M 2016 A well-defined low-valent cobalt catalyst \(\text{ Co }(\text{ PMe }_{3})_{4}\) with dimethylzinc: a simple catalytic approach for the reductive dimerization of benzyl halides New J. Chem. 40 9912; (c) In: Ranu B C 2000 Eur. J. Org. Chem. 2000 2347; (d) \(\text{ Fe(acac) }_{3}\)/Mg: Xu X, Cheng D and Pei W 2006 Iron catalyzed homocoupling of bromide compounds J. Org. Chem. 71 6637; (e) La: Nishino T, Watanabe T, Okada M, Nishiyama Y and Sonoda N 2002 Reduction of organic halides with lanthanum metal: A novel generation method of alkyl radicals J. Org. Chem. 67 966; (f) \(\text{ NiCl }_{2}\)/Sm: Liu Y, Xiao S, Qi Y and Du F 2017 Reductive homocoupling of organohalides using nickel(II) chloride and samarium metal Chem. Asian J. 12 673; (g) \(\text{ NiCl }_{2}\)(\(\text{ PPh }_{3})_{2}\)/Zn, Mg: Mboyi C D, Gaillard S, Mabaye M D, Pannetier N and Renaud J-L 2013 Straightforward synthesis of substituted dibenzyl derivatives Tetrahedron 69 4875; (h) Ni(\(\text{ PPh }_{3}\))\(\text{(NHC)Br }_{2}\)/Mg: Zhang J, Lu G, Xu J, Sun H and Shen Q 2016 Nickel-Catalyzed reductive cross-coupling of benzyl chlorides with aryl chlorides/fluorides: A one-pot synthesis of diarylmethanes Org. Lett. 18 2860; (j) \(\text{ RhCl }(\text{ PPh }_{3})_{3}\)/Zn: Sato K, Inoue Y, Mori T, Sakaue A, Tarui A, Omote M, Kumadaki I and Ando A 2014 Csp3-Csp3 Homocoupling reaction of benzyl halides catalyzed by rhodium Org. Lett. 16 3756Google Scholar
  7. 7.
    (a) Fe/Cu: Liu J and Li B 2016 Facile synthesis of bibenzyl by reductive homocoupling of benzyl halides in aqueous media Synth. Commun. 37 3273; (b) \(\text{ Ni/Al }_{2}\text{ O }_{3:}\) Khan S, Ghatak A and Bhar S 2015 Reductive homocoupling of benzylic halides in aqueous medium using recyclable alumina-supported nickel nanoparticles Tetrahedron Lett. 56 2480; (c) \(\text{ Mn/CuI }_{2}\): Ma J and Chan T H 1998 Wurtz-coupling of alkyl halides with manganese/cupric chloride in aqueous media Tetrahedron Lett. 39 2499; (d) Zn/CuI: De S A C P F, Pontes G M A, Anjos J A L D, Santana S R, Bieber L W and Malvestiti I 2003 Reductive coupling reaction of benzyl, allyl and alkyl halides in aqueous medium promoted by zinc J. Braz. Chem. Soc. 14 429Google Scholar
  8. 8.
    Groll K, Blumke T D, Unsinn A, Haas D and Knochel P 2012 Direct Pd-catalyzed cross-coupling of functionalized organoaluminum Reagents Angew. Chem. Int. Ed. 51 11157CrossRefGoogle Scholar
  9. 9.
    Romney D K, Arnold F H, Lipshutz B H and Li C-J 2018 Chemistry Takes a Bath: Reactions in Aqueous Media J. Org. Chem. 83 7319 and references thereinCrossRefGoogle Scholar
  10. 10.
    For benzylaluminium intermediate in organic solvent, the methylene proton appears at 1.66 and 1.81 ppm. Please see: Bulmke T D, Groll K, Karaghiosoff K and Knochel P 2011 New preparation of benzylic aluminium and zinc organometallics by direct insertion of aluminium powder Org. Lett. 13 6440Google Scholar

Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  1. 1.School of Basic SciencesIndian Institute of Technology BhubaneswarArgul, KhurdaIndia

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