C O M M U N I C A T I O N S
Table 2. Nickel-Catalyzed Cross-Couplings of Secondary Alkyl
Bromides with Trifluoroarylsilanes (eq 1)
Supporting Information Available: Experimental procedures and
compound characterization data. This material is available free of charge
References
(1) For reviews, see: (a) Cross-Coupling Reactions: A Practical Guide;
Miyaura, N., Ed.; Topics in Current Chemistry Series 219; Springer-
Verlag: New York, 2002. (c) Handbook of Organopalladium Chemistry
for Organic Synthesis; Negishi, E.-i., Ed.; Wiley-Interscience: New York,
2002.
(2) For overviews of the difficulties associated with cross-coupling alkyl
electrophiles, see: (a) Ca´rdenas, D. J. Angew. Chem., Int. Ed. 2003, 42,
384-387. (b) Luh, T.-Y.; Leung, M.-k.; Wong, K.-T. Chem. ReV. 2000,
100, 3187-3204.
(3) Couplings with organoboron compounds: (a) Ishiyama, T.; Abe, S.;
Miyaura, N.; Suzuki, A. Chem. Lett. 1992, 691-694. (b) Netherton, M.
R.; Dai. C.; Neuschu¨tz, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123,
10099-10100. (c) Kirchhoff, J. H.; Netherton, M. R.; Hills, I. D.; Fu, G.
C. J. Am. Chem. Soc. 2002, 124, 13662-13663, and references therein.
(4) Couplings with organozinc compounds: (a) Devasagayaraj, A.; Stu¨de-
mann, T.; Knochel, P. Angew. Chem., Int. Ed. Engl. 1995, 34, 2723-
2725. (b) Jensen, A. E.; Knochel, P. J. Org. Chem. 2002, 67, 79-85, and
references therein. (c) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125,
12527-12530.
(5) Couplings with organomagnesium compounds: (a) Terao, J.; Watanabe,
H.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2002, 124,
4222-4223. (b) Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am.
Chem. Soc. 2003, 125, 5646-5647. (c) Frisch, A. C.; Shaikh, N.; Zapf,
A.; Beller, M. Angew. Chem., Int. Ed. 2002, 41, 4056-4059. (d) Frisch,
A. C.; Rataboul, F.; Zapf, A.; Beller, M. J. Organomet. Chem. 2003, 687,
403-409.
(6) Couplings with organotin compounds: (a) Menzel, K.; Fu, G. C. J. Am.
Chem. Soc. 2003, 125, 3718-3719. (b) Tang, H.; Menzel, K.; Fu, G. C.
Angew. Chem., Int. Ed. 2003, 42, 5079-5082.
(7) Couplings with organosilicon compounds: Lee, J.-Y.; Fu, G. C. J. Am.
Chem. Soc. 2003, 125, 5616-5617.
(8) Couplings with organozirconium compounds: Wiskur, S. L.; Korte, A.;
Fu, G. C. J. Am. Chem. Soc. 2004, 126, 82-83.
(9) Sonogashira reactions: Eckhardt, M.; Fu, G. C. J. Am. Chem. Soc. 2003,
125, 13642-13643. For reactions with alkynyllithiums, see: Yang,
L.-M.; Huang, L.-F.; Luh, T.-Y. Org. Lett. 2004, 6, 1461-1463.
(10) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 14726-14727 (nickel
catalyst).
(11) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 1340-1341 (nickel
catalyst).
a Isolated yield, average of two runs. b Starting material: exo/endo )
96/4; product: exo/endo ) 94/6. c Starting material: exo/endo ) 6/94;
product: exo/endo ) 95/5. d 9% NiBr2‚diglyme, 10% bathophenanthroline.
e Starting material: cis/trans ) 95/5; product: cis/trans ) 55/45.
(12) (a) Donkervoort, J. G.; Vicario, J. L.; Jastrzebski, J. T. B. H.; Gossage,
R. A.; Cahiez, G.; van Koten, G. J. Organomet. Chem. 1998, 558, 61-
69 (copper catalyst). (b) Tsuji, T.; Yorimitsu, H.; Oshima, K. Angew.
Chem., Int. Ed. 2002, 41, 4137-4139 (cobalt catalyst). (c) Brinker, U.
H.; Ko¨nig, L. Chem. Ber. 1983, 116, 882-893 (iron catalyst). (d)
Nakamura, M.; Matsuo, K.; Ito, S.; Nakamura, E. J. Am. Chem. Soc. 2004,
126, 3686-3687 (iron catalyst). (e) Nagano, T.; Hayashi, T. Org. Lett.
2004, 6, 1297-1299 (iron catalyst).
Table 3. Nickel-Catalyzed Cross-Couplings of Alkyl Halides with
Trifluoroarylsilanes
(13) For reviews of the Hiyama reaction, see: (a) Hiyama, T. In Metal-
Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.;
Wiley-VCH: New York, 1998; Chapter 10. (b) Hiyama, T.; Shirakawa,
E. Top. Curr. Chem. 2002, 219, 61-85.
(14) For leading references to some recent developments in Hiyama cross-
coupling chemistry, see: (a) Denmark, S. E.; Sweis, R. F. J. Am. Chem.
Soc. 2004, 126, 4876-4882. (b) Itami, K.; Nokami, T.; Yoshida, J.-i. J.
Am. Chem. Soc. 2001, 123, 5600-5601. (c) Seganish, W. M.; DeShong,
P. J. Org. Chem. 2004, 69, 1137-1143.
(15) Furthermore, the method that we have described for cross-couplings of
organosilicon compounds with primary alkyl halides (catalytic PdBr2/P(t-
Bu)2Me; TBAF; THF, rt)(ref 7) is ineffective (<5% yield).
(16) Presumably, the fluoride ion binds to trifluorophenylsilane to generate a
hypervalent silicate that efficiently transfers the phenyl group from silicon
to nickel. For a discussion, see ref 13.
(17) Notes: (a) The stoichiometry of CsF is important: smaller and larger
amounts lead to lower yields. (b) Other Lewis bases (e.g., KOSiMe3,
NaOH, NaOEt, and KOt-Bu) are ineffective. (c) Addition of 1 equiv of
water results in a substantial decrease in yield.
a Isolated yield, average of two runs. For the reaction conditions, see eq
1. b 9% NiBr2‚diglyme, 10% bathophenanthroline, the starting material and
the product are exclusively the exo isomer.
groups such as lactones, acetals, and nitriles with the reaction
conditions.
(18) Trifluoroarylsilanes are easily prepared from trichloroarylsilanes under a
variety of conditions. For example, see: Damrauer, R.; Simon, R. A.;
Kanner, B. Organometallics 1988, 7, 1161-1164 and references therein.
(19) Notes: (a) On a 10 mmol scale (1.65 g of product), the coupling depicted
in entry 12 of Table 2 proceeds in 68% yield. (b) The only identifiable
byproduct is the biaryl (typically <5% yield). (c) Among the silanes that
we have examined to date, the trifluoroarylsilanes are uniquely effective
(<10% yield for the coupling of PhSi(OMe)3, PhSiCl3, PhSiF2Me,
PhSiMe2OH, or PhSi(-CH2CH2CH2-)Me with Cy-Br). (d) These
conditions have not proved to be suitable (<10% yield) for couplings of:
primary or secondary alkyl chlorides or tosylates, secondary alkyl halides
that bear an electron-withdrawing group in the R or â position, and
trifluoroalkenylsilanes.
In summary, we have developed the first metal-catalyzed cross-
couplings of organosilicon compounds with secondary alkyl halides.
Two noteworthy features of the method are its high functional-
group compatibility and the air stability of the catalyst components.
Primary alkyl halides can also be coupled by this catalyst.
Additional efforts to expand the scope of metal-catalyzed cross-
coupling reactions of alkyl electrophiles are underway.
Acknowledgment. Support has been provided by the NIH
(NIGMS, R01-GM62871), the Natural Sciences and Engineering
Research Council of Canada (postdoctoral fellowship to D.A.P.),
Merck, and Novartis.
(20) We believe that these reactions proceed via alkyl radicals that combine
with nickel to form alkylnickel intermediates.
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J. AM. CHEM. SOC. VOL. 126, NO. 25, 2004 7789