Copper + nickel-in-charcoal (Cu-Ni/C): A bimetallic, heterogeneous catalyst for cross-couplings

Article abstract of DOI:10.1021/ol801676u

(Chemical Equation Presented) A new heterogeneous catalyst composed of copper and nickel oxide particles supported within charcoal has been developed. It catalyzes cross-couplings that traditionally use palladium, nickel, or copper, including Suzuki-Miyaura reactions, Buchwald-Hartwig aminations, vinylalane alkylations, etherifications of aryl halides, aryl halide reductions, asymmetric conjugate reductions of activated olefins, and azide-alkyne "click" reactions.

Full text of DOI:10.1021/ol801676u

ORGANIC
LETTERS
2008
Vol. 10, No. 19
4279-4282
Copper + Nickel-in-Charcoal (Cu-Ni/C):
A Bimetallic, Heterogeneous Catalyst for
Cross-Couplings
Bruce H. Lipshutz,* Danielle M. Nihan, Ekaterina Vinogradova, Benjamin R. Taft,
ˇ
and Zarko V. Bosˇkovic´
Department of Chemistry & Biochemistry, UniVersity of California,
Santa Barbara, California 93106
lipshutz@chem.ucsb.edu
Received July 23, 2008
ABSTRACT
A new heterogeneous catalyst composed of copper and nickel oxide particles supported within charcoal has been developed. It catalyzes
cross-couplings that traditionally use palladium, nickel, or copper, including Suzuki-Miyaura reactions, Buchwald-Hartwig aminations, vinylalane
alkylations, etherifications of aryl halides, aryl halide reductions, asymmetric conjugate reductions of activated olefins, and azide-alkyne
“click” reactions.
Transition-metal-based heterogeneous catalysis offers attrac-
tive opportunities in “green” chemistry. Aside from features
commonly highlighted in this regard, including simplicity
of workup, recyclability, and minimization of metallic waste,1
solid supports have the potential to house more than one
metal and, hence, catalyze multiple types of bond construc-
tions. Such “multifunctional” catalysts (Figure 1) are very
few in number, as Felpin and Fouquet have discussed in their
timely review on this subject.2 Our contributions in hetero-
geneous catalysis have focused on the use of carbon as the
matrix into which metals are readily impregnated. Both
activated charcoal and less costly graphite can be used en
route to nickel-in-charcoal (Ni/C),3a nickel-on-graphite
(Ni/Cg),3b and copper-in-charcoal (Cu/C).3c Base metals such
as copper and nickel, in the form of their nitrate salts, are
readily adsorbed; the resulting catalysts mediate a variety
of “name” reactions typically associated with group 10 and
11 transition metals.
(1) Sheldon, R. A.; Arends, I.; Hanefeld, U. Green Chemistry and
Catalysis; Wiley-VCH: Weinheim, 2007.
(2) Felpin, F.-X.; Fouquet, E. ChemSusChem., DOI: 10.1002/
cssc.200800110.
(3) (a) Lipshutz, B. H.; Blomgren, P. A. J. Am. Chem. Soc. 1999, 121,
5819–5820. (b) Lipshutz, B. H.; Frieman, B. A.; Butler, T.; Kogan, V.
Angew. Chem., Int. Ed. 2006, 45, 800–803. (c) Lipshutz, B. H.; Frieman,
B. A.; Tomaso, A. E. Angew. Chem., Int. Ed. 2006, 45, 1259–1264. (R)-
DTBM-SEGPHOS ) (R)-(-)-5,5′-bis[di(3,5-di-tert-butyl-4-methoxyphos-
phino)]-4,4′-bi-1,3-benzodioxole. CAS registry no. 566940-03-2.
10.1021/ol801676u CCC: $40.75
Published on Web 09/03/2008
2008 American Chemical Society

Ni), again loading the metals in a sequential fashion. In this
case, both copper- and nickel-catalyzed reactions could be
performed with rates comparable to those observed with
Cu/C and Ni/C used independently. Finally, a third-genera-
tion catalyst was prepared, further streamlining the procedure
by simultaneously loading both copper and nickel on the
charcoal support, again in a 1:4 ratio. That is, by simply
combining 2% Cu(NO3)2, 8% Ni(NO3)2, activated charcoal,
and water in one pot followed by brief ultrasonication (so
as to distribute and impregnate these salts into the charcoal
matrix), subsequent distillation of the water and drying under
vacuum provides active 2Cu-8Ni/C.
Figure 1. Prospects for heterogeneous multifunctional metal
catalysts.
Cross-Couplings Catalyzed by 2Cu-8Ni/C. Cu-Ni/C
catalyzes Suzuki-Miyaura couplings of aryl bromides and
chlorides with aryl boronic acids in good yields (Table 1).
Heterogeneous bimetallic catalysts, on the other hand, may
exploit three additional elements of practicality: (1) reduction
of the mass of solid support otherwise involved for each
metal if used individually; (2) application to reactions that
either require, or are aided by, a second metal (e.g.,
Sonogashira or Stille couplings, respectively); and (3) utility
in tandem processes that enlist each metal independently in
a one-pot sequence. While reports on Pd-Co/Si,4a Pd-Os/
LDH,4b and Rh-Pd/Gel4c have appeared, to the best of our
knowledge, no examples of multimetals on carbon are
known, nor are there any catalysts of this type offering the
chemistry of either copper or nickel (let alone both in one
reagent). In this paper, we describe the preparation as well
as several applications of the new catalyst copper + nickel-
in-charcoal (Cu-Ni/C).
Table 1. Cu-Ni/C Catalyzed Suzuki-Miyaura Reactionsa,b
Scheme 1. Preparation of Cu-Ni/C
a The red asterisk indicates a halide coupling partner. b All yields are
for isolated material.
Preparation of Cu-Ni/C (1) (Scheme 1). Initially, the
catalyst was prepared using a 1:1 ratio of aqua-colored
Cu(NO3)2 to green Ni(NO3)2, each being loaded in a
sequential fashion. The resulting species containing an
arbitrarily chosen 5 wt % of Cu and 5 wt % of Ni, while
active for several types of copper-catalyzed reactions, was
relatively inactive insofar as nickel catalysis was concerned
(relative to Ni/C).
Reactions take place in dioxane at 180-200 °C over ca. 1 h
under microwave irradiation. The presence of copper in
Cu-Ni/C in excess of 2.5 wt % has an unfavorable effect
on the reaction, lowering the extent of conversion. A 6- to
10-fold excess of Ph3P to nickel was used in the presence
of potassium fluoride and lithium hydroxide as a base. Under
the investigated conditions, electron-rich aryl halides could
not be successfully coupled. The results are comparable to
those obtained using monometalic catalyst Ni/C.5
A second-generation catalyst was then prepared using a
1:4 ratio of Cu(NO3)2 to Ni(NO3)2 (2 wt % of Cu, 8 wt % of
Anilines and diarylamines can be formed from aryl halides
and primary or secondary alkyl- or arylamines using
2Cu-8Ni/C ligated with DPPF (diphenylphosphinoferrocene;
1-2 equiv relative to Ni). Lithium tert-butoxide, a base
previously identified as crucial for the success of aminations
with Ni/C,5 effected the same transformation with this
bimetallic catalyst as well (Figure 2). Most of the reactions
(4) (a) Park, K. H.; Son, S. U.; Chung, Y. K. Org. Lett. 2002, 4, 4361–
4363. (b) LDHs ) layered double-hydroxides: Choudary, B. M.; Chowdari,
N. S.; Madhi, S.; Kantam, L. M. Angew. Chem., Int. Ed. 2001, 40, 4619–
4623. (c) Gel ) poly-ionic gel: Thiot, C.; Schmutz, M.; Wagner, A.;
Mioskowski, C. Chem.sEur. J. 2007, 13, 8971–8978. (d) Choudary, B. M.;
Madhi, S.; Chowdara, N. S.; Kantam, M. L. Top. Catal. 2004, 29, 183–
187. (e) Arai, M.; Sano, Y.; Yoshida, T.; Fujita, S.; Bhanage, B. M.
Tetrahedron Lett. 2003, 44, 3505–3507.
4280
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Figure 4. Cu-Ni/C-catalyzed carboaluminations/couplings.
Previously successful catalysis by Cu/C of alkyne-azide
reactions8 prompted us to investigate catalyst 1 for these
cycloadditions. Not unexpectedly, Cu-Ni/C along with 1
equivalent of triethylamine led to cycloadditions between
several organic azides and acetylenes at 60 °C within a few
Figure 2. Cu-Ni/C-catalyzed aryl chloride aminations.
investigated were efficient, giving good isolated yields, and
proceeded within 1 h in a microwave reactor at 200 °C.
Heterogeneous reductions (dehalogenation) of aromatic
chlorides can be smoothly accomplished with Cu-Ni/C
ligated with PPh3, along with commercially available
Me2NH·BH3 as a stroichiometric and mild hydride source
(Figure 3).6 The choice of hydride is crucial in that it impacts
Figure 5. Cu-Ni/C-catalyzed “click” reactions.
hours (Figure 5). Isolated yields were quantitative, and the
expected 1,4-regioselectivity was uniformly observed.
Copper-catalyzed conjugate reduction can be effected
with this mixed metal heterogeneous reagent enantiose-
lectively, using nonracemic (R)-DTBM-SEGPHOS3c or
with the achiral ligand bisdiphenylphosphinobenzene
(BDP;9 Figure 6). Challenging ꢀ,ꢀ-disubstituted alkenes
were reduced without difficulties. Reactions could be
performed at rt or at 60 °C in the microwave reactor or
in an ultrasonication bath.
Figure 3. Products of Cu-Ni/C-catalyzed reductions of aryl chlorides.
Key: (a) isolated, chromatographically pure material; (b) GC conver-
sion; (c) run at 120 °C; (d) run at 130 °C; (e) run at 180 °C.
the extent of metal bleed into solution (which is significant,
e.g., with Et3SiH).6 A microwave reactor provides for short
reaction times (0.5 h), and simple filtration of the catalyst
and standard workup gives products in high yields. Unlike
Ni/C, Cu-Ni/C cannot be used for dehalogenation of
substrates that contain ketone functional groups, as significant
amounts of the corresponding alcohol were observed,
indicating that isolated carbonyl groups are competitively
reduced, perhaps by electron-transfer processes or trace
amounts of generated heterogeneous copper hydride.
Carboaluminations of terminal alkynes lead to (E)-viny-
lalanes that can be coupled to benzylic halides using Ni(0)
catalysis.7 As illustrated below (Figure 4), the nickel present
in heterogeneous 2Cu-8Ni/C smoothly assembles the ex-
pected allylated aromatics in good isolated yields.
Etherification of both activated and deactivated aryl
bromides can be achieved using Cu-Ni/C, in this case best
achieved with a loading of 5% of each metal (Figure 7).
1,10-Phenanthroline was used as a ligand for copper and
(5) Lipshutz, B. H.; Frieman, B. A.; Lee, C.-T.; Lower, A.; Nihan, D. M.;
Taft, B. R. Chem. Asian J. 2006, 1, 417–419.
(6) Lipshutz, B. H.; Tomioka, T.; Sato, K. Synlett 2001, 970–973.
(7) Lipshutz, B. H.; Frieman, B. A.; Pfeifer, S. S. Synthesis 2002, 2110–
2116.
(8) Lipshutz, B. H.; Taft, B. R. Angew. Chem., Int. Ed. 2006, 45, 8235–
8238.
(9) Baker, B. A.; Boskovic, Z. V.; Lipshutz, B. H. Org. Lett. 2008, 10,
289–292.
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Scheme 2. Recycling Experiments with Cu-Ni/C
Figure 6. Cu-Ni/C-catalyzed conjugate reductions with CuH. Key:
(a) isolated, purified material; (b) (R)-DTBM-SEGPHOS; (c) using
cat. (BDP)CuH; (d) microwave heating at 60 °C; (e) run at rt.
Cs2CO3 as base.11 Reactions were heated to 200 °C with
microwave irradiation.
Recycling of Cu-Ni/C. Catalyst 1 was tested for recy-
clability in two different sequences: (1) where the copper
nickel and subsequent decomposition. Hence, losses due to
complexation and/or decomposition on the charcoal of the
morpholino product 4 accounted for the lower than expected
overall yield.
Scheme 3. One-Pot Tandem Process Using Cu then Ni
Figure 7. Cu-Ni/C-catalyzed etherifications. Key: (a) isolated,
chromatographically puried material; (b) phenol as limiting reagent;
(c) aryl bromide as limiting reagent.
content was utilized twice in asymmetric hydrosilylations
of enoate 2 (Scheme 2, [A]) and (2) where the Ni in
Cu-Ni/C catalyzed a Suzuki-Miyaura coupling followed
by the Cu component effecting a click [3 + 2] cycloaddition
(Scheme 2, [B]). In both series, catalyst 1 gave results
indicative of good recyclability.
Lastly, a tandem process that illustrates another potential
major benefit of having both metals present in the multi-
functional catalyst 1. An initial click reaction between
bromoacetylene 3 and n-octyl azide followed by amination
(without workup) afforded triazole amine 4 in 54% isolated
yield. Although the initial Huisgen cycloaddition product
could be obtained in 95% yield, the heteroaromatic triazole
initially formed is unfortunately prone toward ligation of
In summary, the first example of a mixed-metal, recyclable
catalyst composed of Cu and Ni is reported that is capable
of mediating both group 10 and group 11 cross-couplings.
Other valued combinations of (base and precious) metals-
in-carbon are under study.
Acknowledgment. Financial support provided by the NSF
and NIH is warmly acknowledged.
Supporting Information Available: Detailed experimen-
tal procedures and spectral data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(10) Lipshutz, B. H.; Frieman, B. A.; Unger, J. B.; Nihan, D. M. Can.
J. Chem. 2005, 83, 606–614.
(11) Lipshutz, B. H.; Unger, J. B.; Taft, B. R. Org. Lett. 2007, 9, 1089–
1092.
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