C O M M U N I C A T I O N S
oxidative addition of organic halide to form [NiII](R)(X), reduction
to [NiI](R), oxidative addition of another organic halide to form
[NiIII](R)(R′)(X), reductive elimination of product (R-R′) to form
[NiI](X), and reduction of [NiI](X) back to [Ni0]. This is analogous
to the mechanisms proposed17 for nickel- or cobalt-catalyzed
reductive homocoupling18 and cross-coupling19 reactions of aryl
halides.
Table 2. Substrate Scope of the Nickel-Catalyzed Reductive
Couplinga
The role of ligand 2 remains unclear at the moment. Reactions
conducted with a 1:1:1 Ni/1/2 ratio did not consume starting
material, and reactions catalyzed by a combination of NiI2 and 2
alone provided poor yields of the cross-coupling product (Table 1,
entry 3). These data imply direct participation of two distinct
catalysts in this reaction.20 Further investigation of this two-ligand
synergistic effect, as well as work to reveal the origin of the ob-
served cross-coupling selectivity, is ongoing. Regardless, this nickel-
catalyzed reductive cross-coupling of alkyl halides with aryl halides
represents an operationally simple, high-yielding method to form
cross-coupled products directly from organic halides.
Acknowledgment. This work was supported by the University
of Rochester. Acknowledgment is made to the donors of the
American Chemical Society Petroleum Research Fund for partial
support of this research.
Supporting Information Available: Experimental procedures,
supporting tables, and characterization data. This material is available
References
(1) Frisch, A.; Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674.
(2) Rudolph, A.; Lautens, M. Angew. Chem., Int. Ed. 2009, 48, 2656.
(3) Numbers of commercially available derivatives reported on Scifinder
Scholar, 2009: 83854 Ar-I; 642 185 Ar-Br vs 2954 Ar-B(OH)2 and 771
alkyl-I; 9856 alkyl-Br vs 183 alkyl-B(OR)2 or 38 alkyl-BF3K.
(4) Sase, S.; Jaric, M.; Metzger, A.; Malakhov, V.; Knochel, P. J. Org. Chem.
2008, 73, 7380.
(5) Amatore, M.; Gosmini, C. Chem. Commun. 2008, 5019.
(6) Czaplik, W. M.; Mayer, M.; Jacobi von Wangelin, A. Angew. Chem., Int.
Ed. 2009, 48, 607.
(7) Krasovskiy, A.; Duplais, C.; Lipshutz, B. H. J. Am. Chem. Soc. 2009, 131,
15592.
(8) See Table S4 in the Supporting Information for detailed data on the amounts
of homocoupling and reduction products for the reactions in Table 2.
(9) See the Supporting Information.
(10) Excess nickel was employed in all of the reactions because excess ligand
was found to slightly diminish the yield (see page S3 in the Supporting
Information).
(11) Anhydrous-grade DMPU is available from Aldrich for a similar price to
DMF, and removal in workup requires only filtration through silica gel.
(12) RMnX reagents have been reported to react with ketones to form alcohols
rapidly at room temperature. See: Cahiez, G.; Normant, J. F. Tetrahedron
Lett. 1977, 18, 3383.
a As in Table 1, footnote a, but on a 1 mmol scale. b Isolated yield of
purified product. Average of two runs. c Only bipyridine 1 (0.10 mmol)
was used. d Longer reaction times (26-37 h) were required. e Using 1.2
equiv of 2-bromoheptane (technical grade). f 3p/branched isomer/linear
isomer selectivity ) 89:7:4. g A 95:5 mixture of 3p and 3-phenylheptane
was obtained.
over 1-phenylheptane and other branched isomers was high.
Formation of the isomeric n-alkyl and branched products from
secondary alkyl halides in cross-coupling reactions is known to
occur14 but is minimized in our new procedure.
(13) (a) Yashima, E.; Nimura, T.; Matsushima, T.; Okamoto, Y. J. Am. Chem.
Soc. 1996, 118, 9800. (b) Zheng, S.-L.; Reid, S.; Lin, N.; Wang, B.
Tetrahedron Lett. 2006, 47, 2331.
The previously reported couplings of alkyl halides with aryl
halides appear to involve the formation of discrete organometallic
reactants, such as alkyl-ZnI5,7 or alkyl-MgBr.6 Several pieces of
evidence argue against an analogous mechanism invoking the
intermediacy of an RMnX species in our new nickel-catalyzed
process: (1) consistent with literature precedent,15 direct insertion
of Mn0 does not occur on a time scale that is competitive with the
reaction (Tables S1 and S29); (2) use of a nonmetallic reducing
agent, 1,1,2,2-tetrakis(dimethylamino)ethylene (TDAE),16 in place
of Mn0 produces an appreciable amount of product (Table 1, entry
11); (3) the reaction tolerates electrophilic functionality12 and acidic
protons (Table 2); and (4) reactions run using an anhydrous source
of nickel [Ni(cod)2] form the same high yield of product as reactions
run with a nickel hydrate (0.4 equiv of H2O). Instead, we propose
that the reaction proceeds by initial reduction of [NiII] to [Ni0],
(14) For recent work addressing this problem, see: (a) Dreher, S. D.; Dormer,
P. G.; Sandrock, D. L.; Molander, G. J. Am. Chem. Soc. 2008, 130, 9257.
(b) Han, C.; Buchwald, S. L. J. Am. Chem. Soc. 2009, 131, 7532.
(15) Cahiez, G.; Duplais, C.; Buendia, J. Chem. ReV. 2009, 109, 1434.
(16) Kuroboshi, M.; Waki, Y.; Tanaka, H. J. Org. Chem. 2003, 68, 3938.
(17) (a) Tsou, T. T.; Kochi, J. K. J. Am. Chem. Soc. 1979, 101, 7547. (b)
Amatore, C.; Jutand, A. Organometallics 1988, 7, 2203. (c) Klein, A.;
Budnikova, Y. H.; Sinyashin, O. G. J. Organomet. Chem. 2007, 692, 3156.
(18) (a) Ullmann, F.; Bielecki, J. Chem. Ber. 1901, 34, 2174. (b) Hassan, J.;
Se´vignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. ReV. 2002, 102,
1359. (c) Moncomble, A.; Floch, P. L.; Gosmini, C. Chem.sEur. J. 2009,
15, 4770.
(19) (a) Hassan, J.; Hathroubi, C.; Gozzi, C.; Lemaire, M. Tetrahedron 2001,
57, 7845. (b) Wang, L.; Zhang, Y.; Liu, L.; Wang, Y. J. Org. Chem. 2006,
71, 1284. (c) Amatore, M.; Gosmini, C. Angew. Chem., Int. Ed. 2008, 47,
2089. (d) Gosmini, C.; Bassene-Ernst, C.; Durandetti, M. Tetrahedron 2009,
65, 6141.
(20) Shibasaki, M.; Yamamoto, Y. Multimetallic Catalysis in Organic Synthesis;
Wiley-VCH: Weinheim, Germany, 2004; p 310.
JA9093956
9
J. AM. CHEM. SOC. VOL. 132, NO. 3, 2010 921