ORGANIC
LETTERS
2
001
Vol. 3, No. 12
869-1871
Efficient Scavenging of Ph P and
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1
Ph PdO with High-Loading Merrifield
3
Resin
Bruce H. Lipshutz* and Peter A. Blomgren
Department of Chemistry and Biochemistry, UniVersity of California,
Santa Barbara, California 93106
Received April 1, 2001
ABSTRACT
A simple, highly effective method for removing triphenylphosphine and/or triphenylphosphine oxide from reaction mixures is described.
Commercially available high-loading chloromethylated polystyrene 1, modified in situ with NaI, acts as a scavenger resin. Several coupling
reactions catalyzed by Pd(0) or Ni(0) which require the removal of triphenylphosphine are tested.
Metal-catalyzed cross-coupling reactions are among the most
highly valued methods in organic synthesis. Recent advances
3 3
selective protocol for scavenging Ph P, as well as Ph PdO,
1
which relies on commercially available Merrifield resin.
Conceptually, exposure of high-loading Merrifield resin
1 (4.38 mmol of Cl/g) to triphenylphosphine should remove
the phosphine as its derived phosphonium salt. However,
presumably due in part to the hindrance of the polymer
backbone and poor leaving group ability, access to the
benzylic site is denied and no displacement occurs at ambient
temperatures in a polar medium such as acetone. Upon
addition of NaI, however, stirring overnight at room tem-
in synthetic technology associated with group 10 metal-
mediated processes have propelled Pd-, and to a lesser
2
degree, Ni-based chemistry to the forefront of the field.
While ligandless conditions can occasionally be used to great
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advantage, most reactions rely on phosphine-ligated species
throughout the sequence, with triphenylphosphine being the
most heavily used and least expensive. Removal of this
highly nonpolar phosphine from reaction mixtures after
workup can be problematic, especially in cases where
products of similar polarity are involved. One potential
solution has recently been described involving a PEG-
perature leads to complete disappearance of the Ph P in
3
solution, as analyzed by TLC, capillary GC, and the increase
in weight of the polymer. Resin loadings on the order of 3.1
4
dichlorotriazine as scavenger of various nucleophiles.
mmol of Ph P/g could be routinely realized, although further
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5
a-c
Alternative approaches (e.g., resin-bound phosphines)
development of this method relied on standardized conditions
and workups designed to specifically address such issues
have been developed: however, these rely either on ad-
ditional chemistry done in the presence of the desired
using 1 g of resin to remove 2 mmol of phosphine at 25 °C.
Tests of this method were conducted under “real” coupling
conditions, not only to assess effectiveness but to evaluate
the impact on yields of desired coupling products. With a
5
d,e
product(s) or expensive sulfonated phosphine ligands in
solution.5 We now describe a very simple, expedient, and
f,g
1c
preponderance of Pd(Ph P) -catalyzed processes, the 4:1
3
4
ratio of phosphine to metal can lead to substantial levels of
(1) (a) Schlosser, M. Organometallics in Synthesis-A Manual; John Wiley
&
Sons: New York, 1994 (b) Stang, P.; Diederich, F. Metal-Catalyzed
Cross Coupling Reactions; VCH: Weinheim, 1998. (c) Tsuji, J. Palladium
Reagents and Catalysts-InnoVations in Organic Synthesis; John Wiley &
Sons: New York, 1995.
(5) (a) Amos, R. A.; Emblige, R. W.; Havens, N. J. Org. Chem. 1983,
48, 3598. (b) Guly a´ s, H.; AÄ rva, P.; Bakos, J. Chem Commun. 1997, 2385.
(c) Tunoori, A. R.; Dinah, D.; Georg, G. I. Tetrahedron Lett. 1998, 39,
8751. (d) Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 6054.
(e) Starkey, G. W.; Parlow, J. J.; Flynn, D. L. Bioorg. Med. Chem. Lett.
1998, 8, 2385. (f) Kattesh, V. K.; Hariprasad, G.; Charles, J. S.; Douglas,
E. B. Acc. Chem. Res. 1999, 32, 9. (g) Cornils, B. Org. Process Res. DeV.
1998, 2, 121.
(
2) For one recent example, see: Dai, C.; Fu, G. C. J. Am. Chem. Soc.
001, 123, 2719 and references therein.
3) Reetz, W. M.; Westermann, E. Angew. Chem., Int. Ed. 2000, 39,
65. Beletskaya, I. P.; Cheprakov A. V. Chem. ReV. 2000, 100, 3009.
4) Falchi, A.; Taddei, M. Org. Lett. 2000, 2, 3429.
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0.1021/ol0159219 CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/19/2001