Journal of the American Chemical Society
COMMUNICATION
Table 4. Room-Temperature Asymmetric α-Arylation of
Ketones with Chloro- and Bromoarenes Catalyzed by
[(R)-BINAP]Ni(η2-NC-Ph)a
the Ni(0) or Ni(II) species. Like the dibenzylidene acetone in
electron-rich L2Pd(dba) complexes,16,17 the COD in [(R)-
BINAP]Ni(COD) and related complexes is slow to dissociate
and makes the oxidative addition of haloarenes to the Ni(0)
species slow. However, the discrete Ni(0) precursor [(R)-
BINAP]Ni(η2-NC-Ph) (4) adds chloro- and bromoarenes rapidly
at room temperature, and this high rate allows the α-arylation
of ketones also to occur at room temperature and attenuate
the decomposition to form the less selective Ni(I) species.
Future work will focus on asymmetric α-arylation reactions of
other types of carbonyl compounds and on additional cross-
coupling reactions initiated with discrete Ni(0) complexes
ligated by benzonitrile and bidentate phosphines.
’ ASSOCIATED CONTENT
S
Supporting Information. Detailed experimental proce-
b
a Conditions: ketone (0.200 mmol), ArX (0.400 mmol), NaOtBu (0.400
mmol), and[(R)-BINAP]Ni(η2-NC-Ph) (0.010 mmol, 5% or 0.020 mmol,
10%) in toluene (1.0 mL); ee was determined by chiral HPLC analysis. b 10
mol % catalyst. c 5 mol % catalyst.
dures, characterizations of all compounds, and X-ray crystal-
lographic data (CIF) for compounds 2, 4, 5, and 6. This material
’ AUTHOR INFORMATION
4,40-bis(trifluoromethyl)-1,10-biphenyl (detected by GCꢀMS)
(eq 3). Both 5 and 6 are paramagnetic, and their structures were
determined by single-crystal XRD (see the SI for structural data).
Corresponding Author
’ ACKNOWLEDGMENT
This work was supported by the NIH (GM-58108).
’ REFERENCES
(1) Johansson, C. C. C.; Colacot, T. J. Angew. Chem., Int. Ed. 2010, 49, 676.
(2) For an alternative approach to asymmetric α-arylation of carbonyl
compounds involving the coupling of α-halocarbonyl compounds with
organometallic reagents, see: (a) Dai, X.; Strotman, N. A.; Fu, G. C. J. Am.
Chem. Soc. 2008, 130, 3302. (b) Lou, S.; Fu, G. C. J. Am. Chem. Soc. 2010,
132, 1264. (c) Lundin, P. M.; Fu, G. C. J. Am. Chem. Soc. 2010, 132, 11027.
(3) Burtoloso, A. C. B. Synlett 2009, 320.
(4) Liao, X.; Weng, Z.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 195.
(5) Ahman, J.; Wolfe, J. P.; Troutman, M. V.; Palucki, M.; Buchwald,
S. L. J. Am. Chem. Soc. 1998, 120, 1918.
(6) Lee, S.; Hartwig, J. F. J. Org. Chem. 2001, 66, 3402.
(7) Hamada, T.; Chieffi, A.; Ahman, J.; Buchwald, S. L. J. Am. Chem.
Soc. 2002, 124, 1261.
(8) K€undig, E. P.; Seidel, T. M.; Jia, Y.-x.; Bernardinelli, G. Angew.
Chem., Int. Ed. 2007, 46, 8484.
The reactions of 2-methyl-1-indanone with electronically
varied chloro- and bromoarenes catalyzed by Ni(I) halides 5
and 6 (Table S1 in the SI) were slower than those catalyzed by
nitrile complex 4. Reactions catalyzed by 5 or 6 did not occur at
room temperature, and the reactions at 80 °C formed the α-aryl
indanones in low yields (13ꢀ49%). Moreover, the product ee's
were only 50ꢀ89% for reactions of the chlorides catalyzed by 5
and 7ꢀ51% for reactions of the bromides catalyzed by 6. These
data imply that the loss of activity and enantioselectivity during
the reactions of bromides results from competing reactions
catalyzed by accumulating Ni(I) species.
The oxidative additions of chloro- and bromoarenes to 4 at
room temperature suggest that the catalytic process could also
occur at this mild temperature.15 As shown in Table 4, both
chloro- and bromoarenes reacted with 2-methyl-1-indanone in high
yields and enantioselectivities (entries 1ꢀ10) at room temperature.
Under these mild conditions, the difference in enantioselectivities
with chloro- and bromoarenes was small for most reactions. The
reaction of 2-methyl-1-tetralone with 4-chlorobenzotrifluoride,
however, did occur with significantly higher enantioselectivity than
that of 4-bromobenzotrifluoride (entries 11 and 12).
(9) García-Fortanet, J.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008,
47, 8108.
(10) Taylor, A. M.; Altman, R. A.; Buchwald, S. L. J. Am. Chem. Soc.
2009, 131, 9900.
(11) Spielvogel, D. J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 3500.
(12) Chen, G. C.; Kwong, F. Y.; Chan, H. O.; Yub, W.-Y.; Chan,
A. S. C. Chem. Commun. 2006, 1413. For additional discussion of this
reference, see the SI.
(13) D€obler, C.; Kreuzfeld, H. J.; Michalik, M.; Krause, H. W.
Tetrahedron: Asymmetry 1996, 7, 117.
(14) Jiang, L.; Weist, S.; Jansat, S. Org. Lett. 2009, 11, 1543.
(15) For prior asymmetric α-arylation of ketones with a Pdꢀmono-
phosphine system, see ref 7.
(16) Amatore, C.; Jutand, A.; Khalil, F.; M’Barki, M. A.; Mottier, L.
Organometallics 1993, 12, 3168.
In summary, the α-arylations of ketones with aryl and hetero-
aryl chlorides catalyzed by the combination of Ni(COD)2 and
(R)-BINAP (for α-arylation) or (R)-DIFLUORPHOS (for α-
heteroarylation) occur with high enantioselectivity. In contrast to
the usual reactivity of haloarenes, bromoarenes reacted with
lower yield and enantioselectivity than the corresponding chlor-
oarenes, most likely because of greater reactivity of the bromoar-
ene through a less selective catalyst formed by decomposition of
(17) Amatore, C.; Broeker, G.; Jutand, A.; Khalil, F. J. Am. Chem. Soc.
1997, 119, 5176.
16333
dx.doi.org/10.1021/ja2082087 |J. Am. Chem. Soc. 2011, 133, 16330–16333