C-C Bond Formation Catalyzed Heterogeneously by Nickel-on-Graphite (Ni/C)

Article abstract of DOI:10.1021/ol702453q

Inexpensive nickel(II) mounted on graphite (Ni C_g) can be easily activated and used to heterogeneously catalyze cross-couplings involving aryl halides/tosylates with boronic acids, vinylalanes, and vinylzirconocenes. Comparisons are made with the charcoal analogue, Ni/C, and some unusual chemoselectivities between these catalysts have been uncovered.

Full text of DOI:10.1021/ol702453q

ORGANIC
LETTERS
2008
Vol. 10, No. 5
697-700
C−C Bond Formation Catalyzed
Heterogeneously by Nickel-on-Graphite
(Ni/Cg)
Bruce H. Lipshutz,* Tom Butler, and Elizabeth Swift
Department of Chemistry and Biochemistry, UniVersity of California, Santa Barbara,
California 93106
lipshutz@chem.ucsb.edu
Received October 26, 2007
ABSTRACT
Inexpensive nickel(II) mounted on graphite (Ni/Cg) can be easily activated and used to heterogeneously catalyze cross-couplings involving aryl
halides/tosylates with boronic acids, vinylalanes, and vinylzirconocenes. Comparisons are made with the charcoal analogue, Ni/C, and some
unusual chemoselectivities between these catalysts have been uncovered.
Graphite: an especially stable allotropic form of carbon
characterized by unsaturated sheets separated by 3.35 Å. As
a solid support harboring metal atoms capable of catalyzing
carbon-carbon bond formations, it offers very attractive
economics (being less expensive than charcoal), a freely
flowing nature (that makes handling quite convenient), and
unlike charcoal, a well-ordered array (that could translate
into chemoselectivity differences between metal-impregnated
derivatives). Mounting Ni(II) between layers of graphite
(Ni/Cg; eq 1) leads to an effective catalyst containing
nanometer blobs of metal distributed randomly throughout
the layers (Figure 1).1 Upon conversion to active nickel(0)
using n-BuLi in THF (15 min, rt), aromatic tosylates and
mesylates can be reduced with excellent functional group
tolerance using in situ formed K+ or Cs+ salts of com-
mercially available Me2NH‚BH3 as a mild source of hydride.2
The ability of Ni/Cg to insert into aryl C-OTs/C-OMs
bonds,1 rather than relying on more activated and costly
triflates,3 suggested that cross-couplings with various orga-
nometallics should take place to afford valued carbon-
carbon bonds under heterogeneous conditions. In this letter
we describe the first Ni/Cg-catalyzed C-C bond-forming
(1) Lipshutz, B. H.; Frieman, B. A.; Butler, T. Angew. Chem., Int. Ed.
2006, 45, 800; Angew. Chem. 2006, 118, 814.
(2) Lipshutz, B. H.; Tomioka, T.; Pfeiffer, S. Tetrahedron Lett. 2001,
42, 7737.
(3) Sasaki, K.; Kubo, T.; Sakai, M.; Kuroda, Y. Chem. Lett. 1997,
617.
10.1021/ol702453q CCC: $40.75
© 2008 American Chemical Society
Published on Web 02/13/2008

Table 1. Comparison of Ni/C vs Ni/Cg in Suzuki Couplings
Figure 1. TEM of Ni/Cg showing graphite sheets and dark blobs
of nickel.
reactions, using boronicacids, vinylzirconocenes, and viny-
lalanes as coupling partners (eq 2).
a Isolated, chromatographically purified material. b Reaction was allowed
to stir overnight at reflux. c Under microwave conditions at 180 °C.
Suzuki Couplings. Ni/Cg-catalyzed Suzuki couplings were
studied extensively with the intent to make comparisons with
the corresponding reactions using Ni/C (nickel-in-charcoal)4
and to examine both aryl halides and toslylates as educts
(Tables 1, 2, respectively). In general, Ni/Cg proved to be
as effective, within experimental error, or better as a catalyst
than Ni/C. That is, couplings were faster (extent of conver-
sion was greater for a given time), yields were higher (by
isolation), and the overall quality of the reactions appeared
to be cleaner (by TLC). Aryl chlorides (entries A-D) and
bromides (entries E, F) coupled with boronic acids either
under conditions of conventional heating in refluxing diox-
ane, or with microwave assistance.5
effective at mediating the desired biaryl bond formation was
unexpected (entry C). This was the first of such chemose-
lectivity differences between catalysts to be noted (vide
infra).
Cases of aryl tosylates that, as anticipated (vide supra),
likewise afforded biaryl products in good isolated yields are
less common (Table 2). Examples of both activated and
deactivated partners suggest a reasonably broad scope
associated with this process. With a temperature increase
from 180 °C to 200 °C, expected shorter reaction times were
observed without erosion in yields (entries 2, 4 vs 3, 5, 6).
Here again, Ph3P was the ligand of choice;4 attempts to use,
for example, S-Phos,6 led to no conversion under otherwise
identical conditions (as in entry 3). Particularly noteworthy
is the observation that little-to-no homocoupling of either
the aryl tosylate or boronic acid was seen in these reactions.
Surprisingly, neither aryl nor alkyl trifluoroborates7 coupled
with aryl tosylates, even under microwave conditions (200
°C) involving an activated substrate (Scheme 1).
The observation that, while the deactivated and somewhat
sterically hindered case of o-chloroanisole was unresponsive
to Ni/C, the graphite-supported catalyst (Ni/Cg) was very
(4) Lipshutz, B. H.; Sclafani, J. A.; Blomgren, P. A. Tetrahedron 2000,
56, 2139.
(5) (a) Tierney, J. P., Lidstrom, P., Eds. MicrowaVe Assisted Organic
Synthesis; Blackwell: Oxford, 2005. (b) Bose, A. K.; Manhas, M. S.;
Ganguly, S. N.; Sharma, A. H.; Banik, B. K. Synthesis 2002, 1578. (c)
Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250; Angew. Chem. 2004,
116, 6408. (d) For a recent review on heterogeneous reactions in catalysis
assisted by microwave irradiation, see: Desai, B.; Kappe, C. O. Top. Curr.
Chem. 2004, 242, 177.
(6) Barder, T. E.; Buchwald, S. L. Org. Lett. 2004, 6, 2649.
(7) (a) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 4, 275. (b)
Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393. (c) Darses, S.; Michaud,
G.; Genet, J. P. Eur. J. Org. Chem. 1999, 8, 1875.
698
Org. Lett., Vol. 10, No. 5, 2008

Scheme 2. Recycling the Catalyst
Table 2. Suzuki Couplings with Aryl Tosylates
(Scheme 3). Such a coupling between these two types of
partners appears to be unprecedented. Octyne (7) was treated
under newly developed conditions leading to full control of
regiochemistry in Negishi carboalumination to 8,8 using a
pre-equilibrated reagent derived from Me3Al (1.5 equiv),
catalytic Cp2ZrCl2 (5 mol %), and isobutylaluminoxane
(IBAO; 10 mol %) in toluene at room temperature. Subse-
quent coupling with aryl tosylate 9 gave the corresponding
styrene derivative 10 in good isolated yield.
a Isolated, chromatographically purified material. b At 200 °C. c GC
conversion, to known biaryl (see SI). d At 180 °C.
Scheme 3. Carboalumination/Cross-coupling: Vinylalane +
Aryl Tosylate
Catalyst recycling was demonstrated by the successive
cross-couplings illustrated in Scheme 2. Thus, following the
Ni/Cg-catalyzed coupling of boronic acid 1 (1.5 equiv) with
bromide 2 to biaryl 3, filtration returned Ni/Cg that was used
directly upon reactivation with n-BuLi, along with introduc-
tion of fresh reagents. Cross-coupling between deactivated
boronic acid 4 and tosylate 5 gave diaryl ketone 6 in good
yield.
Carboalumination/Cross-Coupling. One representative
example of a Ni/Cg-catalyzed cross-coupling between an in
situ formed vinylalane and an aryl tosylate was investigated
Hydrozirconation/Cross-Coupling. Prior studies using
Ni/C have shown that this catalyst can assist in couplings
between in situ formed vinylzirconocenes and aryl halides.9
Likewise, Ni/Cg can be used for this purpose, where iodides,
bromides, and chlorides undergo cross-couplings to E-
substituted styrenes (Table 3). Both rates and efficiencies
were found to be as good or better with Ni/Cg. Unfortunately,
neither type of Negishi reaction with vinylzirconocenes10 or
Scheme 1. Attempted Couplings with Trifluoroborate Salts
(8) Lipshutz, B. H.; Butler, T.; Lower, A.; Servesko, J. Org. Lett. 2007,
9, 3737.
(9) Lipshutz, B. H.; Frieman, B. Tetrahedron 2004, 60, 1309.
(10) Negishi, E.; Van Horn, D. E. J. Am. Chem. Soc. 1977, 99, 3168.
Org. Lett., Vol. 10, No. 5, 2008
699

Scheme 4. Chemoselectivity between Catalysts in Aminations
Table 3. Ni/Cg-Catalyzed Cross-Couplings with Vinyl-
zirconocenes
product 12 was detected by GC from the combination of
morpholine and activated chloride 11. While potentially
synthetically valuable, an explanation for this chemoselec-
tivity is not apparent.
In summary, nickel-on-graphite (Ni/Cg), a safe and espe-
cially inexpensive material, can be used to catalyze cross-
couplings with various organometallic reagents (boronic
acids, and vinylic zirconocenes and alanes) and aryl halides
as well as, in some cases, aryl tosylates. This catalyst tends
to afford cleaner reactions relative to its charcoal predecessor.
Unexpected chemoselectivities between nickel-on-graphite,
or nickel-in-charcoal (Ni/C), have been discovered and may
provide rare opportunities in heterogeneous catalysis.
a At 200 °C. b Isolated.
their derived zinc halide derivatives11 led to C-C bond
formation with aryl tosylates at temperatures up to 200 °C.
Chemoselectivity in Aminations: Ni/C vs Ni/Cg. At-
tempts to utilize Ni/Cg to catalyze aminations of aryl
chlorides were surprisingly unsuccessful, notwithstanding
prior observations where Ni/C has been shown to effect aryl
C-N bond constructions readily, even under conditions of
conventional heating in refluxing dioxane (Scheme 4).12
Thus, it was quite unexpected that none of the aminated
Acknowledgment. Financial support provided by the NIH
(GM 40287) is warmly acknowledged. We are indebted to
Dr. Louise Weaver (University of New Brunswick) for TEM
data.
(11) Negishi, E., Ed. Handbook of Organopalladium Chemistry for
Organic Synthesis; Wiley: New York, 2002. (b) Tsuji, J. Palladium
Reagents and Catalysts: New PerspectiVes for the 21st Century; Wiley:
New York, 2004.
(12) Lipshutz, B. H.; Ueda, H. Angew. Chem., Int. Ed. 2000, 39, 4492;
Angew. Chem. 2000, 112, 4666.
Supporting Information Available: Procedures and full
characterization of new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
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