ORGANIC
LETTERS
2
004
Vol. 6, No. 14
305-2308
Scavenging and Reclaiming Phosphines
Associated with Group 10
2
Metal-Mediated Couplings
Bruce H. Lipshutz,* Bryan Frieman, and Henrik Birkedal†
Department of Chemistry and Biochemistry, UniVersity of California,
Santa Barbara, California 93106
Received February 23, 2004
ABSTRACT
Exposure of any of several mono- or bidentate phosphines to CuCl leads to quick removal of unwanted ligands from solution. Most phosphines,
if desired, can be easily recovered.
Many of the most popular group 10 transition-metal-
catalyzed coupling reactions (e.g., Suzuki, Negishi, Stille,
Sonogashira, etc.) routinely rely on phosphine ligands. Their
and general method for both sequestering and subsequently
recovering phosphines from a variety of metal-catalyzed
bond-forming reactions.
1
removal from crude reaction mixtures can oftentimes be
nontrivial, in some cases forcing additional chemistry to be
done solely for this purpose (e.g., oxidation with peroxides).
Development of this protocol was an outgrowth of the
fundamental studies by several groups on the role of CuI in
2
5
Pd-catalyzed Stille couplings. Contributions by Farina,
5
6
7
8
Although a report from our laboratories in 2001 suggested
Liebeskind, Espinet, Corey, and others have provided
strong evidence that Cu(I) withdraws Ph P (and to a far lesser
extent Ph As) from the coordination sphere of a Pd(II)
3
that Merrifield resin could serve to effectively remove Ph
3
P,
3
ideally an inexpensive method that applies to a wide range
of phosphines both mono- and bidentate in nature would be
welcomed. Moreover, ligands far more precious than Ph P
3
3
intermediate, thereby accelerating transmetalation. On this
basis, we surmised that CuCl might be very capable of
sequestering phosphines. This was readily tested by dissolv-
are often essential for a given transformation, in particular
when such species are the source of reagent chirality. The
option for their recovery and hence reuse, especially in
industrial-scale situations, constitutes yet another worthy
3 2 2
ing Ph P in CH Cl or THF followed by addition of 0.33-
0.50 equiv of CuCl at ambient temperatures. Within 10 min,
TLC indicated that all of the phosphine had precipitated from
solution in the form of its CuCl complex. Similar observa-
4
goal. We now describe a very straightforward, inexpensive,
3 2
tions were made for Ph P in Et O and toluene. The
†
stoichiometry of the adduct follows from that of known
Solved the X-ray structure of (R)-SEGPHOS-CuCl.
(
1) (a) Agrofoglio, L. A.; Gillaizeau, I.; Saito, Y. Chem. ReV. 2003, 103,
1
875. (b) Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029.
(5) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L. S.
J. Org. Chem. 1994, 59, 5905.
(6) Casado, A. L.; Espinet, P. Organometallics 2003, 22, 1305.
(7) Han, X.; Stoltz, B. M.; Corey E. J. J. Am. Chem. Soc. 1999, 121,
7600.
(8) For example, cf.: Piers, E.; McEachern, E. J.; Romero, M. A.
Tetrahedron Lett. 1996, 37, 1173.
(
(
(
2) Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 6054.
3) Lipshutz, B. H., Blomgren, P. Org. Lett. 2001, 3, 1869.
4) (a) Asymmetric Catalysis on Industrial Scale; Blaser, H. U., Schmidt,
E., Eds.; Wiley-VCH: Weinheim, 2004. (b) Heterogeneous Catalysis and
Fine Chemicals IV; Blaser, H. U., Baiker, A., Prins, R., Eds.; Elsevier:
Amsterdam, 1997.
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0.1021/ol049681j CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/11/2004