Ni(II)/Al(0) mediated benzylic Csp 3 - Csp 3 coupling in aqueous media

Article abstract of DOI:10.1007/s12039-019-1638-1

Abstract : 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-, NO ₂-, Ph- as well as 2 ^° benzyl halides. Graphical abstract: The reagent combination of aluminium metal and catalytic Ni(NO3)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. [Figure not available: see fulltext.].

Full text of DOI:10.1007/s12039-019-1638-1

J. Chem. Sci.
(2019) 131:59
© Indian Academy of Sciences
https://doi.org/10.1007/s12039-019-1638-1
REGULAR ARTICLE
Ni(II)/Al(0) mediated benzylic Csp3-Csp3 coupling in aqueous
media
MUKESH KUMAR NAYAK, PRIYABRATA MUKHI, ANURADHA MOHANTY,
SOHEL SAMIM RANA, RAJAT ARORA, HIMANI NARJINARI and SUJIT ROY∗
School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Argul, Khurda, Odisha 752 050, India
E-mail: sujitroy.chem@gmail.com; sroy@iitbbs.ac.in
MS received 7 February 2019; revised 26 April 2019; accepted 2 May 2019
Abstract. 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-, NO2-, Ph- as well as 2◦ benzyl halides.
Keywords. C-C bond formation; reaction in water; aluminium; nickel; benzyl halide.
1. Introduction
and co-workers on the generation of benzylic aluminum
sesquichlorides from corresponding benzyl halide and
aluminum powder in the presence of catalytic In(III)
halide in THF is worthy of mention here.8 The benzyl
aluminum reagents were transmetallated to the corre-
sponding benzyl zinc reagents and subsequently used
for coupling reactions.
In this manuscript, we demonstrate a highly facile
homocoupling of benzyl bromide to the corresponding
bibenzyl in the presence of aluminum powder (1.2 eqv.)
and catalytic Ni(II) salt in water at room temperature.
To our knowledge, this is the first example of the use
of aluminum metal in C-C coupling in water and adds
to its green relevance. Studies on the effect of solvent
clearly showed the superiority of water over a host of
other organic solvents.
Carbon-carbon bond formation via coupling reactions
is one of the most fundamental transformations in
organic synthesis.1 The well-known oxidative addition–
transmetallation– reductive elimination sequence is in
the textbook premise. On a relative scale, coupling
reactions involving organometallic partner bearing sp
and sp2 hybridized carbons2 outwits those having sp3-
hybridized carbon centers.3 In this regard we were
drawn to the Csp3-Csp3 homocoupling of benzylic
halides leading to bibenzyl derivatives, the latter being
key building blocks for the synthesis of dyes, poly-
mers, agrochemicals and pharmaceuticals.4 Although
Wurtz coupling is historically the first in alkyl and aryl
homocoupling,5 the post-Wurtz era showed the advent
of many reagents for benzylic homocoupling which
include either a metal or the dual reagent combination
of a metal and a catalytic transition metal partner.6 Also
interesting are the examples of benzylic homocoupling
in aqueous medium7 which are of relevance in the con-
text of green chemistry.
2. Experimental
2.1 General procedure for the homo-coupling of
benzyl halides
Although aluminium metal has similar electronega-
tivity as zinc, examples of benzylic activation by alu- To a suspension of aluminium powder (1.2 eq) in water (5
mL), Ni(NO3)2.6H2O (10 mol%) was added and the reaction
minium metal is lesser explored. The work of Knochel
*
For correspondence
Electronic supplementary material: The online version of this article (https://doi.org/10.1007/s12039-019-1638-1) contains
supplementary material, which is available to authorized users.
0123456789().: V,-vol

59 Page 2 of 6
J. Chem. Sci.
(2019) 131:59
mixture was degassed using argon. The suspension was stirred Table 2. Homo-coupling of benzyl bromide using
Ni(II)/Al(0): Effect of solvents.a
at room temperature for 5 min. Benzyl halide (3 mmol) was
added slowly to the reaction mixture, and the mixture was
stirred at room temperature for 48 h under argon. The mixture
slowly turned into a clear solution and the bibenzyl crys-
tals were seen to be floating on top of the solution. The
mixture was quenched with hydrochloric acid (4M, 5 mL)
and extracted with dichloromethane. The combined organic
Entry
Solvent
Yield of 2a (%)b
extract was washed with water and dried over Na2SO4.
The solvent was removed and the residue was purified by
chromatography or recrystallization. All products gave satis-
factory spectroscopic data and were compared with authentic
sample wherever available.
1
2
3
4
5
6
DCM
DMF
Toluene
Acetonitrile
Methanol
H2O
< 5
< 5
Nil
Nil
< 5
82
a1a(3mmol), Al(1.2eqv.), solvent(5mL), roomtemperature.
brefers to isolated yield of pure product after chromatogra-
phy/crystallization.
3. Results and Discussion
In the initial screening, we tested the reaction of benzyl
bromide 1a with various metals in water at room temper-
ature under argon atmosphere. In the case of Sn, Zn and
Al metals, bibenzyl 2a was obtained in 35, 47 and 58%
yields respectively. Next, we explored the reaction of 1a
in the presence of aluminium metal (1.2 eqv.) and a cat-
alytic 3d-transition metal salt (Table 1). In the absence
of a catalyst, the yield of 2a was 58% (Table 1, entry 1).
As catalyst FeCl3 and CoCl2 could not improve the yield
(entries 8, 9). On the other hand, water-soluble Ni(II)
salts showed significant catalytic effect (entries 2, 4–7).
Among various nickel salts, Ni(NO3)2.6H2O was found
to be most efficient. After 48 h, the reaction mixture
became fully transparent with crystals of 2a floating on
top; the latter was isolated in 82% yield (Table 1, entry
6). A similar reaction but with aluminium foil yielded
2a in 65% yield (entry 7).
The water-effect9 in the present reaction became glar-
ing when we studied the reaction in various organic
solvents (Table 2). None of the solvents tried, including
polar protic, polar aprotic, as well as non-polar solvents,
could facilitate the reaction in a manner that water did.
Trace amounts of the product were detected for reac-
tions in methanol, DMF and DCM. As stated earlier, in
water, the mixture turned in to a clear solution on com-
pletion of the reaction. The clear solution showed a pH
value between 6–7 (pH paper).
A recent paper on the reductive coupling of benzyl
halides using catalytic Ni(0)-on-alumina in the presence
of hydrazine hydrate as co-reductant is noteworthy.7b
Encouraged by this report we attempted the reaction of
1a (3 mmol) with 80% hydrazine hydrate (2 mL) in
water. The colour of the mixture instantly changed from
green to pink. Even after 48 h, there was no conversion
of 1a, which was isolated back in quantitative yield.
The scope of the present reaction was tested with var-
ious substituted benzyl bromide and benzyl chlorides
1a–1n using aluminum powder (1.2 eqv.) and nickel
nitrate hexahydrate (10 mol %) as a catalyst in aqueous
medium and at room temperature (Table 3). The follow-
ing results are noteworthy. Benzyl bromides were more
reactive than benzyl chlorides, while aryl halides were
completely non-reactive (entries 1–3, 7, 10–12, 14, 15–
17). Secondary benzyl halides were also amenable to the
reaction(entries8, 9). Bothelectronsdonating(entries2,
3, 12, 13) and withdrawing (entries 4–7, 14) substituent
on the benzene ring were tolerated. The attempted reac-
tion between benzyl bromide and bromobenzene in the
presence of Ni(II)/Al did not result in the formation of
diphenyl methane as the cross-coupled product.
Table 1. Homo-coupling of benzyl bromide using
Al(0)/transition metal salts in water.a
Entry
Catalyst
Yield of 2a (%)b
1
2
3
4
5
6
7
8
9
nil
58
70
57
62
70
82
65c
60
50
NiCl2.6H2O
NiCl2(PPh3)2
NiBr2
Ni(acac)2
Ni(NO3)2.6H2O
Ni(NO3)2.6H2O
CoCl2
FeCl3
a1a (3 mmol), Al (1.2 eqv.), water (5 mL), room temperature.
brefers to isolated yield of pure product after chromatog-
c
raphy/crystallization. aluminium powder was replaced by
finely cut pieces from an aluminium foil.

J. Chem. Sci.
(2019) 131:59
Page 3 of 6
59
Table 3. Homo-coupling of benzyl bromide using Ni(II)/Al(0): Substrate Scope.a
Entry
1
Substrate
Product
Yield of
2 (%)b
82
Br
1a
2a
2
3
4
90
70
68
Br
1b
2b
Cl
Br
1c
Cl
2c
2d
Cl
Cl
Br
1d
Cl
Cl
CN
5
6
60
68
Br
1e
NC
2e
NC
Br
1f
2f
7
62

59 Page 4 of 6
Table 3. (contd.)
J. Chem. Sci.
(2019) 131:59
8
26
9
71
10
11
24
40
2a
CH3
2b
H3C
Cl
Cl
12
13
5
2c
nil
14
15
10
nil
16
17
nil
nil
a1 (3 mmol), Al (1.2 eqv.), water (5 mL), room temperature. brefers to isolated yield of pure product
after chromatography/crystallization.

J. Chem. Sci.
(2019) 131:59
Page 5 of 6
59
3.1 1H NMR monitoring of reaction mixture
Liu N 2012 Nickel catalysed cross-coupling with pin-
cer ligands Eur. J. Inorg. Chem. 901; (g) Grzybowski M,
Skonieczny K, Butenschçn H and Gryko D T 2013 Com-
parison of oxidative aromatic coupling and the scholl
reaction Angew. Chem. Int. Ed. 52 9900
The reaction of aluminium metal with benzyl bromide
in water being novel, we explored the reaction by H
1
NMR in D2O as solvent (Supplementary Information).
A mixture of aluminium powder (96 mg, 3.6 mmol) and
benzyl bromide (3 mmol) in D2O (4 mL) was stirred.
After 24 h, the mixture was separated into two parts. In
one part, CDCl3 was added and the organic phase was
subjected to NMR analysis (Figure S1a, Supplemen-
tary Information,). The other part in D2O was directly
checked for NMR using tert-butanol as internal standard
(Figure S1b, Supplementary Information,). The organic
phase showed the presence of bibenzyl and unreacted
benzyl bromide. The aqueous phase indicated the for-
mation of a new product with methylene proton at 1.88
ppm, and phenyl proton at 6.9–7.1 ppm indicating the
presence of a benzyl group in the product.10 Attempts
to run ESI-MS of the solution is in progress.
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 pro-
moted by an NiCl2/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 (X = 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 homocou-
pling 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 N2H4 as
traceless mediator for homo- and crossaryl coupling Nat.
Commun. 9 4739
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 transi-
tion 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 cat-
alysts 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 2251
4. Conclusions
In conclusion, we have demonstrated a simple and prac-
tical method for homocoupling of benzyl halides using
aluminium powder and nickel nitrate as a catalyst under
mild conditions in an aqueous medium. Further work in
extending the scope of the reaction is in progress.
Supplementary Information (SI)
General methods, spectral data and figures are available at
www.ias.ac.in/chemsci.
Acknowledgements
The authors thank the Institute for support including fellow-
ship.
References
4. (a) Cirla A and Mann J 2003 Combretastatins: from nat-
ural products to drug discovery Nat. Prod. Rep. 20 558;
(b) Baur J A and Sinclair D A 2006 Therapeutic poten-
tial of resveratrol: the in vivo evidence Nat. Rev. Drug
Discov. 5 493
5. (a) Wurtz A 1855 Ann. Chim. Phys. 44 275; (b) Wurtz A
1855 Ann. Chem. Pharm. 96 364
6. (a) VCl2(Py)4: Cooper T A 1973 Reductive coupling of
aralkyl halides by vanadium(II) J. Am. Chem. Soc. 95
4158; (b) Co(PMe3)4/Zn: Fallon B J, Corce V, Ama-
tore M, Aubert C, Chemla F, Ferreira F, Luna A P
and Pitit M 2016 A well-defined low-valent cobalt cat-
alyst Co(PMe3)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) Fe(acac)3/Mg: Xu X, Cheng D and
Pei W 2006 Iron catalyzed homocoupling of bromide
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
AandCanturkB2009Organotrifluoroboratesandmono-
coordinated palladium complexes as catalysts–A perfect
combinationforsuzuki–miyauracouplingAngew. Chem.
Int. Ed. 48 9240; (c) Mesganaw T and Garg N K 2013
Ni and Fe Catalyzed cross-coupling reactions of phe-
nol derivatives Org. Process Res. Dev. 17 29; (d) Li H,
Johansson Seechurn C C C and Colacot T J 2012 Devel-
opment 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 synthe-
sis Angew. Chem. Int. Ed. 49 9047; (f) Wang Z-X and

59 Page 6 of 6
J. Chem. Sci.
(2019) 131:59
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) NiCl2/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) NiCl2(PPh3)2/Zn, Mg: Mboyi C D, Gail-
lard S, Mabaye M D, Pannetier N and Renaud J-L 2013
Straightforward synthesis of substituted dibenzyl deriva-
tives Tetrahedron 69 4875; (h) Ni(PPh3)(NHC)Br /Mg:
Zhang J, Lu G, Xu J, Sun H and Shen Q 2016 N2ickel-
Catalyzed reductive cross-coupling of benzyl chlorides
with aryl chlorides/fluorides: A one-pot synthesis of
diarylmethanes Org. Lett. 18 2860; (j) RhCl(PPh3)3/Zn:
Sato K, Inoue Y, Mori T, Sakaue A, Tarui A, Omote M,
Kumadaki I and Ando A 2014 Csp3-Csp3 Homocou-
pling of benzylic halides in aqueous medium using recy-
clable alumina-supported nickel nanoparticles Tetrahe-
dronLett. 562480;(c)Mn/CuI2:MaJandChanTH1998
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 Reduc-
tive coupling reaction of benzyl, allyl and alkyl halides in
aqueous medium promoted by zinc J. Braz. Chem. Soc.
14 429
8. Groll K, Blumke T D, Unsinn A, Haas D and Knochel P
2012 Direct Pd-catalyzed cross-coupling of functional-
ized organoaluminum Reagents Angew. Chem. Int. Ed.
51 11157
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 therein
pling reaction of benzyl halides catalyzed by rhodium 10. For benzylaluminium intermediate in organic solvent,
Org. Lett. 16 3756
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 alu-
minium powder Org. Lett. 13 6440
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) Ni/Al2O3:
Khan S, Ghatak A and Bhar S 2015 Reductive homocou-