COMMUNICATIONS
to confirm the expected linear structure of the complex. Such
selective measurements of intergroup separations of several
nanometers should thus open up a new route for the structural
determination of noncrystalline supramolecular assemblies.
Suzuki Cross-Couplings of Alkyl Tosylates that
Possess b Hydrogen Atoms: Synthetic and
Mechanistic Studies**
Matthew R. Netherton and Gregory C. Fu*
Experimental Section
During the past few decades, remarkable progress has been
reported in the development of mild and efficient nickel- and
palladium-catalyzed protocols for carbon carbon bond-form-
ing reactions of electrophiles that contain C(sp2)-X bonds
(e.g., aryl and vinyl halides and sulfonates).[1] In contrast,
general methods to cross-couple unactivated electrophiles
that contain C(sp3)-X bonds, especially when b hydrogen
atoms are present in the molecule, are scarce, presumably
because of slow oxidative addition and/or facile b-hydride
elimination (Scheme 1).[2] In the case of alkyl halides, some
advances have been described, specifically, examples of
Suzuki cross-couplings of alkyl iodides, bromides, and chlor-
ides,[3] Negishi reactions of alkyl iodides and bromides,[4] and
Kumada couplings of alkyl bromides and a chloride.[5]
Synthesis and full characterization of ligand 2 is described in the Supporting
Information.
EPR measurements: Four-pulse DEER time domain signals were ob-
tained with the sequence (p/2)n1 t1 (p)n1 t (p)n2 t1 þ t2 tꢀ(p)n1 t2 echo at
a temperature of 15 K on a Bruker E 580 X-Band spectrometer. A
Bruker Flexline split-ring resonator ER 4118X-MS3 was used with over-
coupling to Q ꢁ 100. Pump pulses were generated by feeding the output of
an HP8350B sweep oscillator to one microwave-pulse-forming unit of the
spectrometer. All pulse lengths were 32 ns, the dwell time was 8 ns, and the
fixed interpulse delays were t1 ¼ 400 ns and t2 ¼ 1200 ns (Figure 3a c) or
t2 ¼ 2000 ns (Figure 3d). Details are discussed in the Supporting Informa-
tion.
Received: July 4, 2002 [Z19663]
[1] a) J. M. Lehn, Angew. Chem. 1990, 102, 1347 1362; Angew. Chem.
Int. Ed. Engl. 1990, 29, 1304 1319; b) J. M. Lehn, Pure Appl. Chem.
1994, 66, 1961 1966; c) J.-P. Sauvage, M. W. Hosseini in Comprehen-
sive Supramolecular Chemistry, Vol. 9 (Eds.: J. L. Atwood, D. M.
Macnicol, F. Vˆgtle, J.-M. Lehn), Elsevier, Oxford, 1996; d) P. N. W.
Baxter, J. M. Lehn, B. O. Kneisel, G. Baum, D. Fenske, Chem. Eur. J.
1999, 5, 113 120.
oxidative
addition
reductive
elimination
LnPd0
R
X
R
R'
[2] A. Schweiger, G. Jeschke, Principles of pulse electron paramagnetic
resonance, OUP, Oxford, 2001.
R
R
LnPd
LnPd
[3] a) Biological Magnetic Resonance, Vol. 19 (Eds.: L. J. Berliner, S. S.
Eaton, G. R. Eaton), Kluwer, Amsterdam, 2000; b) P. P. Borbat, J. H.
Freed, Chem. Phys. Lett. 1999, 313, 145 154; c) G. Jeschke, M.
Pannier, A. Godt, H. W. Spiess, Chem. Phys. Lett. 2000, 331, 243 252;
d) G. Jeschke, Macromol. Rapid Commun. 2002, 23, 227 246.
[4] R. Codd, A. V. Astashkin, A. Pacheco, A. M. Raitsimring, J. H.
Enemark, J. Biol. Inorg. Chem. 2002, 7, 338 350.
R'
X
β-hydride
elimination
(undesired)
M X
M R'
H
X
R
LnPd
transmetalation
[5] M. Huber, I. M. C. van Amsterdam, M. Ubbink, G. W. Canters,
Biophys. J. 2002, 82, 2328.
Scheme 1. Generalized mechanism for palladium-catalyzed cross-coupling
reactions.
[6] a) M. Seiter, V. Budker, J.-L. Du, G. R. Eaton, S. S. Eaton, Inorg.
Chim. Acta 1998, 273, 354 366; b) S. S. Eaton, G. R. Eaton in
Biological Magnetic Resonance, Vol. 19 (Eds.: L. J. Berliner, S. S.
Eaton, G. R. Eaton), Kluwer, Amsterdam, 2000, pp. 348 381.
[7] a) C. Altenbach, T. Marti, H. G. Khorana, W. L. Hubbell, Science
1990, 248, 1088 1092; b) W. L. Hubbell, C. Altenbach, Curr. Opin.
Struct. Biol. 1994, 4, 566 573.
[8] a) J. Voss, W. L. Hubbell, H. R. Kaback, Proc. Natl. Acad. Sci. USA
1995, 92, 12300 12303; b) Y. Lu, S. M. Berg, T. D. Pfister, Chem. Rev.
2001, 101, 3047 3080.
In contrast, to the best of our knowledge, at the time that we
initiated our program in this area, there were no reports of
palladium- or nickel-catalyzed cross-couplings of alkyl sulfo-
nates. In the interim, however, Kambe and co-workers have
described nickel-catalyzed Kumada couplings of two unfunc-
tionalized alkyl tosylates.[5] In this communication, we estab-
lish that Pd/PtBu2Me can achieve Suzuki reactions of a range
of functionalized alkyl sulfonates [Eq. (1); 9-BBN ¼ 9-bora-
bicyclo[3.3.1]nonane], and we report preliminary mechanistic
studies of this new catalyst system.
[9] a) A. Khatyr, R. Ziessel, J. Org. Chem. 2000, 65, 3126 3134; b) A. El-
ghayoury, A. Harriman, A. Khatyr, R. Ziessel, Angew. Chem. 2000,
112, 191 195; Angew. Chem. Int. Ed. 2000, 39, 185 189; c) E. C.
Constable, Chem. Commun. 1997, 1073 1080.
[10] A. Godt, C. Franzen, S. Veit, V. Enkelmann, M. Pannier, G. Jeschke, J.
Org. Chem. 2000, 65, 7575 7582.
[11] D. Hartmann, R. Philipp, K. Schmadel, J. J. Birktoft, L. J. Banaszak,
W. E. Trommer, Biochemistry 1991, 30, 2782 2790.
[12] G. Jeschke, A. Koch, U. Jonas, A. Godt, J. Magn. Reson. 2002, 155, 72
mainz.mpg.de/ ~ jeschke/distance.html.
[13] a) R. Allmann, W. Henke, D. Reinen, Inorg. Chem. 1978, 17, 378 382;
b) I. Arriortua, T. Rojo, J. M. Amigo, G. Germain, J. P. Declerq, Acta
Crystallogr. Sect. B 1982, 38, 1323 1324; c) G. D. Storrier, S. B.
Colbran, D. C. Craig, J. Chem. Soc. Dalton Trans. 1997, 3011 3028.
[14] A quantitative analysis of the orientation selection requires additional
information on the experimental coordination geometry and the
orientation of the copper g and hyperfine tensors with respect to the
coordination polyhedron. This analysis is now underway.
[*] Prof. Dr. G. C. Fu, Dr. M. R. Netherton
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, MA 02139 (USA)
Fax : (þ 1)617-258-7500
E-mail: gcf@mit.edu
[**] We thank Johnson Matthey Inc. for supplying palladium compounds.
Support has been provided by the National Institutes of Health
(National Institute of General Medical Sciences, R01-GM62871), the
Natural Sciences and Engineering Research Council of Canada
(postdoctoral fellowship to M.R.N.), and Novartis.
Supporting information for this article is available on the WWW under
3910
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
0044-8249/02/4120-3910 $ 20.00+.50/0
Angew. Chem. Int. Ed. 2002, 41, No. 20