Nickel-Catalyzed Cross-Electrophile Coupling with Organic Reductants in Non-Amide Solvents

Article abstract of DOI:10.1002/chem.201602668

Cross-electrophile coupling of aryl halides with alkyl halides has thus far been primarily conducted with stoichiometric metallic reductants in amide solvents. This report demonstrates that the use of tetrakis(dimethylamino)ethylene (TDAE) as an organic reductant enables the use of non-amide solvents, such as acetonitrile or propylene oxide, for the coupling of benzyl chlorides and alkyl iodides with aryl halides. Furthermore, these conditions work for several electron-poor heterocycles that are easily reduced by manganese. Finally, we demonstrate that TDAE addition can be used as a control element to ‘hold’ a reaction without diminishing yield or catalyst activity.

Full text of DOI:10.1002/chem.201602668

A Journal of
Accepted Article
Title: Nickel-Catalyzed Cross-Electrophile Coupling with Organic Reductants in Non-
Amide Solvents
Authors: Lukiana L. Anka-Lufford; Kierra M. M. Huihui; Nicholas J. Gower; Daniel
John Weix
This manuscript has been accepted after peer review and the authors have elected
to post their Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by using the Digital
Object Identifier (DOI) given below. The VoR will be published online in Early View as
soon as possible and may be different to this Accepted Article as a result of editing.
Readers should obtain the VoR from the journal website shown below when it is pu-
blished to ensure accuracy of information. The authors are responsible for the content
of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201602668
Link to VoR: http://dx.doi.org/10.1002/chem.201602668
Supported by

Chemistry - A European Journal
10.1002/chem.201602668
COMMUNICATION
Nickel-Catalyzed Cross-Electrophile Coupling with Organic
Reductants in Non-Amide Solvents
Lukiana L. Anka-Lufford,[a] Kierra M. M. Huihui,[a] Nicholas J. Gower,[a] and Daniel J. Weix*[a]
Dedication ((optional))
Abstract: Cross-electrophile coupling of aryl halides with alkyl
halides has thus far been primarily conducted with stoichiometric
metallic reductants in amide solvents. This report demonstrates that
the use of tetrakis(dimethylamino)ethylene (TDAE) as an organic
reductant enables the use of non-amide solvents, such as
acetonitrile or propylene oxide, for the coupling of benzyl chlorides
and alkyl iodides with aryl halides. Furthermore, these conditions
work for several electron-poor heterocycles that are easily reduced
by manganese. Finally, we demonstrate that TDAE addition can be
used as a control-element to ‘hold’ a reaction without diminishing
yield or catalyst activity.
While limited progress has been reported in addressing
reductant,[8, 9] solvent,[10] and reactive substrate[1] challenges, we
report here that these challenges can be addressed together
more easily than separately. The organic reductant
tetrakis(dimethylamino)ethylene (TDAE)[11] works better in non-
amide solvents and these conditions avoid formation of
organometal reagents with reactive aryl halides. TDAE is
reported to have similar reducing power to zinc[11, 12] and can be
synthesized on scale from DMF.[ 13 ] Following the pioneering
9g,i]
work of Tanaka,[ 14 ,
we had previously used TDAE as a
mechanistic probe to demonstrate that organozinc or
organomanganese intermediates were not required in cross-
electrophile coupling reactions,[7, 15] but yields had been low.
Cross-electrophile coupling of aryl halides with alkyl halides
has proven to be a versatile method to form Csp2-Csp3 bonds,[1]
even in cases where Suzuki coupling proved challenging.[ 2 ]
Although cross-electrophile coupling avoids the need to preform
an organometal reagent, a metallic powder (Zn or Mn) is the
source of electrons and the reactions are usually run in amide
solvents (Scheme 1). While zinc and manganese are abundant,
the generation of stoichiometric metal salts can complicate
waste disposal[ 3 ] and there is concern about the security of
supplies in the long-term.[4] The reliance on amide and urea
solvents is problematic because several common amide
solvents are increasingly subject to regulation[5] and there is a
strong interest in moving to other solvents.[6] Finally, the use of
Zn or Mn reductants can lead to low yields with highly reactive
organic halides because the formation of organozinc or
organomanganese reagents competes with coupling.[7]
We began our studies by examining reactions of a reactive
alkyl electrophile, benzyl chloride, with iodobenzene in a variety
of solvents (Table 1). We adapted conditions from our previous
work,[7b, 16] but for convenience and cost considerations, we used
the pre-formed catalyst (dtbbpy)NiBr2. We chose this reaction to
start because diarylmethanes
pharmaceutically active molecules[
are found in many
17
, 18 ]
and the cross-
electrophile coupling of benzylic halides with aryl halides had
proven difficult,[17b, 19, 20] possibly because they can react directly
with zinc.
Table 1. Solvent compatibility of TDAE and Zn in cross-electrophile coupling.
I
7 mol% (dtbbpy)NiBr2
Cl
+
reductant (2 equiv)
solvent, 80 oC, 3-48 h
1
2a
3a
1.2 equiv
A. Typical conditions Ni-catalyzed cross-electrophile coupling
Entry
Solvent[a]
DMA
Zinc Yield (%)[b]
TDAE Yield (%)[b]
(dtbbpy)NiBr2
X1
Alkyl
Alkyl
+
Ar
Ar
X2
Zn or Mn reductant
amide or urea solvent
1
2
3
4
5
6
7
8
9
82
15
79
MeCN
88 (90)[c]
102, (90)[d]
75
B. New conditions: no stoichiometric metal, no amide solvent
(dtbbpy)NiBr2
propylene carbonate
diethyl carbonate
IPAc
58
19
53
51
4
X1
Alkyl
Alkyl
+
Ar
Ar
X2
organic reductant (TDAE)
acetonitrile or propylene carbonate
79[e] (83)[f]
76
Scheme 1. Cross-electrophile coupling without stoichiometric metal.
2-Me-THF
toluene
66
2-butanol
64
33[h]
20
sulfolane[g]
49[h]
[a]
Dr. L. L. Anka-Lufford, K. M. M. Huihui, Dr. N. J. Gower, Dr. L. K. G.
Ackerman, Prof. Dr. Daniel J. Weix
Department of Chemistry
[a] Reactions were set up on in a glovebox with dried (<35 ppm H2O) and
degassed solvents unless otherwise noted. [b] Yield is GC yield vs. dodecane,
uncorrected. [c] Reaction set up on benchtop with acetonitrile that was not
degassed or dried (229 ppm H2O). [d] Isolated yield of pure material after
column chromatography. [e] Degassed, but not dried isopropyl acetate. [f]
Isopropyl acetate used as received, 549 ppm H2O, reaction set up on
University of Rochester
Rochester, NY, USA 14627-0216
E-mail: daniel.weix@rochester.edu
Supporting information for this article is given via a link at the end of
the document.

Chemistry - A European Journal
10.1002/chem.201602668
COMMUNICATION
benchtop. [g] This solvent was used as received, reaction set up on benchtop.
[h] GC area %.
We also examined the use of TDAE for the coupling of less
reactive alkyl halides with aryl iodides and bromides (Scheme 3).
We obtained the highest yield in acetonitrile, but propylene
carbonate and 2-butanol also provided good yields (Table S6).
Other green solvents such as diethyl carbonate and isopropyl
acetate gave poor yields due to competing dimerization
reactions (Chart S3). The addition of sodium iodide was
beneficial, as we have previously observed.[7, 16] We observed
higher cross-product yields and less dimerization and reduction
products at higher temperatures when coupling with
bromobenzene (Chart S4). On the other hand, the highest yields
were achieved at lower temperatures when coupling with
iodobenzene due to diminished production of dimethylaniline by-
product (Chart S4). The results for the synthesis of 5a are
superior to our previous results in DMPU with 2.5 equiv of alkyl
halide (54-57% yield).[7b, 15]
Reactions conducted with TDAE generally provided higher
yields than reactions with zinc in a selection of solvents chosen
from available solvent selection guides (Table 1).[21] In contrast
to our previous results under different conditions,[19] we were
able to obtain a high yield of diphenylmethane in DMA with both
zinc and TDAE (tetrakis(dimethylamino)ethylene) (entry 1).
While the highest yields were obtained in MeCN and propylene
carbonate (entries 2 & 3), we also obtained promising yields in
less polar solvents, such as isopropyl acetate (IPAc), 2-
methyltetrahydrofuran (2-Me-THF), and toluene (entries 5-7).[22]
The chemistry is generally robust to trace amounts of water
and oxygen (Table 1, entries 2 & 5). Although TDAE is oxygen
sensitive and must be stored under nitrogen,[11] rigorous
deoxygenation of the solvent did not significantly improve the
reaction yield (Table 1, entries 2 & 5) and reactions could be run
on the bench or in the glovebox. Ligand is required for high
selectivity in reactions with TDAE and without ligand, a large
amount of hydrodehalogenated benzyl chloride (i.e. toluene) is
observed (Table S1, entry 4). Also, the starting materials are
unreactive in the absence of catalyst or TDAE (Table S1, entries
2-3). Furthermore, at lower temperatures, reactions are much
slower but still very selective (Table S2).
10 mol% NiI2•xH2O
10 mol% dtbbpy
25 mol% NaI
+
Alkyl-I
Ar X1
Ar Alkyl
TDAE (1.2 equiv)
2a, g-k
4a-h
5a-h
acetonitrile, 80 °C, 24 h
1.2 equiv
C8H17
Boc
N
5a, X=Br 60%[a]
X= I 75%[b]
5b, X=I 71%[b]
5c, X= I 65%[b]
Most published examples of nickel-catalyzed cross-
electrophile coupling utilize two equivalents of metal reductant;
however, a high yield and a fast reaction time can be achieved
with just 1.2 equivalents of TDAE (Figure S1). Adding more than
1.2 equivalents of TDAE does not significantly increase the rate
of reaction (Figure S1), suggesting reduction of the catalyst is
not turnover-frequency limiting.
C8H17
5e, X= I 85%[c]
C8H17
N
N
N
O
5d, X= Br 75%[a, c]
Substrates that do not work with Mn as the reductant[d]
C8H17
Ts Ts
N
N
N
N
N
O
Our optimized reaction conditions for the arylation of benzyl
chloride with TDAE provided results comparable to our
previously published results with benzyl alcohols (Scheme 2).[17]
5-Bromopyrimidine coupled under these conditions in 61% yield
but was not a good substrate in that previous study.
N
OTBS
5h, X=Br 58%[a, c]
C8H17
5g, X=Br 72%[a, c]
NMe2
5f, X=Br 56%[a, c]
Scheme 3. Aryl/HetAr-X and Alkyl-I Coupling. Yields are of purified product.
[a] Reaction with Alkyl-Br (2 equiv) and pyridine (0.5 equiv). [b] Reaction at
40 °C. [c] Reaction at 60 °C. [d] See Supporting Information for details.
7 mol% (dtbbpy)NiBr2
Cl
Ar
+
Ar
2a-f
I
TDAE (1.2 equiv)
propylene carbonate, 80 °C
24 h
1
3a-f
While TDAE provided yields comparable to reactions
2 equiv
conducted with zinc or manganese for simple substrates (5a,
5c),[15,
results obtained with nitrogen heterocycles[ 23 ] were
7]
N
superior in several useful cases. For example, we obtained a
75% yield of 5d from the coupling of 5-bromopyrimidine with
iodooctane. The one previous example of this substrate for
OMe
N
3a, 90%[a]
3b, 81%
3c, 61%
cross-electrophile coupling required
a
higher loading of
catalyst.[24] More compelling are the results with an electron-poor
bromopyrimidine and a bromopyrazole (5f – 5h). Both of these
substrates directly react with Mn in DMA in the absence of nickel
(Figure S2), a situation that leads to low yields and large
amounts of hydrodehalogenation products.[7b] We obtained no
observable amount of product 5f from reactions with Mn or Zn in
DMA or MeCN, but a 56% yield with TDAE in MeCN. Similarly,
O
Bpin
F
3d, 51%
3e, 60%
3f, 81%[b]
Scheme 2. Nickel-Catalyzed Arylation of Benzyl-Cl. Yields are of purified
product. [a] Reaction with TDAE (2 equiv). [b] Yield of 3f adjusted to account
for 7.4 wt% of biaryl that we were unable to separate by chromatography.

Chemistry - A European Journal
10.1002/chem.201602668
COMMUNICATION
the tosyl-protected bromopyrazole reacts with Mn in DMA
(Figure S2), but couples well in reactions with TDAE in MeCN.
This is the first report of a successful cross-electrophile coupling
of an alkyl halide with a pyrazole, a common heterocycle in
medicinal chemistry.[25]
4-Benzylanisole (3b). In a nitrogen-filled glove box, a 1-dram vial
equipped with a Teflon-coated stir bar was charged with
dtbbpyNiBr2 (17.0 mg, 0.035 mmol, 0.070 equiv), dodecane (10
µL, 0.044 mmol), benzyl chloride (69 µL, 0.60 mmol, 1.2 equiv),
1-iodo-4-methoxybenzene (117 mg, 0.5 mmol), propylene
carbonate (2.0 mL) and TDAE (139.6 L, 0.6 mmol, 1.2 equiv).
The reaction was then capped with a PTFE-faced silicone
septum, removed from the glove box, and stirred at 80 °C in a
reaction block on the bench top. Upon completion (as judged by
GC analysis), the reaction mixture was filtered though a short
plug of silica gel, eluted with diethyl ether, and concentrated
under reduced pressure. Purification by flash chromatography
(5% ethyl acetate in hexanes) afforded 80 mg (81% yield) of the
title compound as a colorless oil. Analytical data matched those
reported in the literature. 1H NMR (500 MHz; CDCl3) δ 7.35 (q, J
= 8.3 Hz, 2H), 7.26-7.24 (m, 3H), 7.18 (d, J = 8.3 Hz, 2H), 6.91
(d, J = 8.6 Hz, 2H), 4.00 (s, 2H), 3.85 (s, 3H). 13C NMR (126
MHz; CDCl3) δ 158.0, 141.7, 133.4, 130.0, 129.8, 128.6, 126.1,
114.0, 55.4, 41.2. GC-MS (EI+) m/z (% rel. int., ion): 198.00
(100.00, M+).
For reactions run on larger scale, a method to control the
reaction progress that allows for the reaction to be stopped and
restarted is highly desirable. In cross-coupling, this is commonly
achieved by slow addition of the carbon nucleophile.[3] Slow
addition of carbon electrophiles in cross-electrophile coupling
does not work because reactions starved of electrophile form
nickel(0) and precipitate nickel metal.[15] We considered that
slow addition of the reductant could enable reversible control
because a reaction starved of reductant will accumulate (L)NiIIX2,
which is a stable precatalyst. Furthermore, TDAE is ideal for this
purpose because it is a liquid. A reaction monitored by 19F NMR
demonstrates the principle (Figure 1). Initially, 0.5 equivalents of
TDAE was added and the reaction went to approximately 50%
conversion. Once the reaction stopped, we held the mixture for
an additional 30 min before adding another 1.2 equiv of TDAE.
The reaction immediately resumed at a similar rate to the initial
reaction and completed in good yield.
Acknowledgements
7 mol% (dtbbpy)NiBr2
I
Acknowledgement is made to the ACS GCI Pharmaceutical
Roundtable Research Grant for support of this research. This
work was also supported in part by Pfizer (NJG). We thank all
the industrial contributors for useful suggestions and comments,
but especially Dr. J. D. Nelson (Pfizer). DJW is a Camille
Dreyfus Teacher-Scholar and a Novartis Early Career Awardee.
We thank Dr. Laura Ackerman (Univ. of Rochester) for initial
experiments demonstrating the potential of TDAE in cross-
electrophile coupling.[19b]
Cl
+
TDAE
acetonitrile-d3, 75 °C
F
F
1
2f
3f
1.2 equiv
Keywords: keyword 1 • keyword 2 • keyword 3 • keyword 4 •
keyword 5
[1] a) C. E. I. Knappke, S. Grupe, D. Gärtner, M. Corpet, C. Gosmini, A. Jacobi
von Wangelin, Chem.–Eur. J. 2014, 20, 6828-6842; b) D. A. Everson, D.
J. Weix, J. Org. Chem. 2014, 79, 4793-4798.
[2] G. A. Molander, K. M. Traister, B. T. O’Neill, J. Org. Chem. 2014, 79, 5771-
5780.
Figure 1. Yield of product 3f vs. time with the addition of 0.5 and 1.2
equivalents of TDAE at 0 and 70 minutes, respectively. The reaction stops at
40 minutes after the first portion of TDAE has been consumed and switched
back on at 70 min upon the second addition of TDAE.
[3] M. Acemoglu, M. Baenziger, C. M. Krell, W. Marterer, in Transition Metal-
Catalyzed Couplings in Process Chemistry (Eds.: J. Magano, J. R.
Dunetz), Wiley-VCH, Weinheim, 2013, pp. 15-23.
[4] The Chemical Innovation Knowledge Transfer Network conducted research
resulting in
a
“Periodic Table of Endangered Elements”.
http://www.acs.org/content/acs/en/greenchemistry/research-
innovation/research-topics/endangered-elements.html
3/23/2016).
In conclusion, we have demonstrated how TDAE, an organic
reductant, can broaden the versatility of nickel-catalyzed cross-
electrophile-coupling. In addition to offering new ways to
address difficult substrates, the use of TDAE avoids the
generation of stoichiometric metallic waste and a need for amide
solvents.
(Accessed
[5] For a succinct summary of current challenges, see: L. J. Diorazio, D. R. J.
Hose, N. K. Adlington, Org. Process Res. Dev. 2016, 20, 760-773.
[6] S. D. Ramgren, L. Hie, Y. Ye, N. K. Garg, Org. Lett. 2013, 15, 3950-3953.
[7] a) S. Biswas, D. J. Weix, J. Am. Chem. Soc. 2013, 135, 16192–16197; b) D.
A. Everson, B. A. Jones, D. J. Weix, J. Am. Chem. Soc. 2012, 134,
6146-6159.
[8] For an example of an intramolecular cross-electrophile coupling of aryl
halides with alkyl halides that uses DMF as the terminal reductant, see:
Experimental Section

Chemistry - A European Journal
10.1002/chem.201602668
COMMUNICATION
H. Liu, J. Wei, Z. Qiao, Y. Fu, X. Jiang, Chem.–Eur. J. 2014, 20, 8308-
8313.
[18] The synthesis of diarylmethanes continues to be an active area of
research, see the previous reference and a) M. Amatore, C. Gosmini,
Chem. Commun. 2008, 5019-5021; b) M. A. Schade, A. Metzger, S.
Hug, P. Knochel, Chem. Commun. 2008, 3046-3048; c) R. B. Bedford,
M. A. Hall, G. R. Hodges, M. Huwe, M. C. Wilkinson, Chem. Commun.
2009, 6430-6432; d) A. D. Benischke, I. Knoll, A. Rerat, C. Gosmini, P.
Knochel, Chem. Commun. 2016, 52, 3171-3174.
[9] Organic reductants have seen sporadic use in other reductive coupling
reactions: a) T. E. Krafft, J. D. Rich, P. J. McDermott, J. Org. Chem.
1990, 55, 5430-5432; b) T. E. Krafft, J. D. Rich, P. J. McDermott, J. Org.
Chem. 1990, 55, 5430-5432; c) D. D. Hennings, T. Iwama, V. H. Rawal,
Org. Lett. 1999, 1, 1205-1208; d) S. Mukhopadhyay, G. Rothenberg, D.
Gitis, H. Wiener, Y. Sasson, J. Chem. Soc., Perkin Trans. 2 1999,
2481-2484; e) S. Mukhopadhyay, G. Rothenberg, H. Wiener, Y. Sasson,
Tetrahedron 1999, 55, 14763-14768; f) S. Mukhopadhyay, G.
Rothenberg, N. Qafisheh, Y. Sasson, Tetrahedron Lett. 2001, 42, 6117-
6119; g) M. Kuroboshi, Y. Waki, H. Tanaka, Synlett 2002, 2002, 637-
639; h) M. Kuroboshi, Y. Waki, H. Tanaka, J. Org. Chem. 2003, 68,
3938-3942; i) T. Kashiwabara, M. Tanaka, Tetrahedron Lett. 2005, 46,
7125-7128; j) Y. Nishiyama, A. Kobayashi, Tetrahedron Lett. 2006, 47,
5565-5567; k) M. Zeng, Y. Du, L. Shao, C. Qi, X.-M. Zhang, J. Org.
Chem. 2010, 75, 2556-2563; l) X. Yu, T. Yang, S. Wang, H. Xu, H.
Gong, Org. Lett. 2011, 13, 2138–2141.
[19] a) D. A. Everson, Nickel-Catalyzed Electrophile Cross-coupling of Aryl
Halides with Alkyl Halides, PhD. Thesis, University of Rochester, May
2013; b) L. K. G. Ackerman, Multimetallic Catalytic Methods for the
Formation of Carbon-Carbon Bonds, University of Rochester, March
2016.
[20] Lipshutz reported that zinc inserts into benzylic halides to form benzylzinc
reagents and that palladium can mediate the coupling of these reagents
with Csp2-X electrophiles. See: a) C. Duplais, A. Krasovskiy, A.
Wattenberg, B. H. Lipshutz, Chem. Commun. 2010, 46, 562-564; b) V.
Krasovskaya, A. Krasovskiy, A. Bhattacharjya, B. H. Lipshutz, Chem.
Commun. 2011, 47, 5717-5719; c) V. Krasovskaya, A. Krasovskiy, B. H.
Lipshutz, Chem. Asian J. 2011, 6, 1974-1976; d) P. Klumphu, B. H.
Lipshutz, J. Org. Chem. 2014, 79, 888-900.
[10] Reasonable results have been obtained in some cases in alcohol solvents,
see reference 2. For a cross-electrophile coupling in THF, see: J.-H. Liu,
C.-T. Yang, X.-Y. Lu, Z.-Q. Zhang, L. Xu, M. Cui, X. Lu, B. Xiao, Y. Fu,
L. Liu, Chem.–Eur. J. 2014, 20, 15334-15338.
[21] a) R. K. Henderson, C. Jimenez-Gonzalez, D. J. C. Constable, S. R.
Alston, G. G. A. Inglis, G. Fisher, J. Sherwood, S. P. Binks, A. D.
Curzons, Green Chem. 2011, 13, 854-862; b) D. Prat, O. Pardigon, H.-
W. Flemming, S. Letestu, V. Ducandas, P. Isnard, E. Guntrum, T.
Senac, S. Ruisseau, P. Cruciani, P. Hosek, Org. Process Res. Dev.
2013, 17, 1517-1525; c) ACS GCI Pharmaceutical Roundtable Solvent
[11] N. Wiberg, Angew. Chem. Int. Ed. Engl. 1968, 7, 766-779; Angew. Chem.
1968, 80, 809-822.
[12] Tuning TDAE can lead to very strong organic reductants. For an account,
see: J. A. Murphy, J. Org. Chem. 2014, 79, 3731-3746.
[13] H. E. Winberg (E. I. du Pont de Nemours and Company), US 3,239,534,
1966.
Selection
Guide
Version
2.0
Issued
March
21,
2011
http://surveys.acs.org/se.ashx?s=04BD76CC0E5496A7
3/24/2016).
(Accessed
[14] M. Kuroboshi, M. Tanaka, S. Kishimoto, K. Goto, M. Mochizuki, H. Tanaka,
Tetrahedron Lett. 2000, 41, 81-84.
[22] We also spent some time examining reactions in water or in water
containing the surfactant Nok,20 but we observed hydrogen gas
production and did not pursue this avenue further. We did not notice
gas production from reactions in 2-butanol.
[15] D. A. Everson, R. Shrestha, D. J. Weix, J. Am. Chem. Soc. 2010, 132,
920-921.
[16] K. A. Johnson, S. Biswas, D. J. Weix, Chem.–Eur. J. 2016, 22, 7399–
7402.
[23] E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57, 10257-
10274.
[17] See L. K. G. Ackerman, L. L. Anka-Lufford, M. Naodovic, D. J. Weix,
Chem. Sci. 2015, 6, 1115-1119 and references cited therein.
[24] D.-J. Cai, P.-H. Lin, C.-Y. Liu, Eur. J. Org. Chem. 2015, 5448-5452.
[25] Ş. G. Küçükgüzel, S. Şenkardeş, Eur. J. Med. Chem. 2015, 97, 786-815.

Chemistry - A European Journal
COMMUNICATION
COMMUNICATION
10.1002/chem.201602668
(dtbbpy)NiBr2
Dr. Lukiana L. Anka-Lufford, Kierra M.
M. Huihui, Dr. Nicholas J. Gower, and
Prof. Daniel J. Weix*[a]*
X1
Alkyl
Alkyl
+
X2
solvent: MeCN,
Me-THF, IPAc, or
propylene carbonate
Ar
Ar
Me2N
Me2N
NMe2
NMe2
Ar = aryl, pyrimidine, pyrazole
Alkyl = benzyl, 1°, 2° alkyl
14 examples
51 - 90% yield
Page No. – Page No.
organic reductant
Nickel-Catalyzed Cross-Electrophile
Coupling with Organic Reductants in
Non-Amide Solvents
Simplified Coupling. Removing the heterogeneous metal reductant and replacing
it with an organic reductant enables the use of a broad range of organic solvents
and electron-poor nitrogen heterocycles in cross-electrophile coupling.
keywords: homogeneous catalysis, nickel, heterocycles, cross-coupling, green chemistry