ORGANIC
LETTERS
2
006
Vol. 8, No. 16
457-3460
Air-Stable PinP(O)H as Preligand for
Palladium-Catalyzed Kumada Couplings
of Unactivated Tosylates
3
Lutz Ackermann* and Andreas Althammer
Department of Chemistry and Biochemistry, Ludwig-Maximilians-UniVersit a¨ t M u¨ nchen,
Butenandtstrasse 5-13, D-81377 M u¨ nchen, Germany
Received May 6, 2006
ABSTRACT
Air-stable and easily accessible PinP(O)H enables highly efficient palladium-catalyzed Kumada cross-coupling reactions of aryl tosylates. The
in situ generated catalyst proved applicable not only to electron-rich and electron-poor carbocyclic tosylates but also to heterocyclic tosylates,
such as pyridine and quinoline derivatives. The results described herein constitute the first use of air-stable secondary phosphine oxides as
preligands for transition-metal-catalyzed coupling reactions between organometallic species and tosylates.
Palladium-catalyzed coupling reactions between organic
electrophiles and organometallic reagents are reliable and
versatile tools for the regioselective formation of carbon-
sium reagents and unactivated aryl tosylates were only
reported for a palladium complex derived from an electron-
rich analogue of a Josiphos ligand.
6
,7
2
1,2
carbon bonds involving two sp -hybridized carbons. Usu-
Recently, we reported on the use of heteroatom-substi-
3
8
ally, aryl triflates, bromides, and more recently chlorides
tuted secondary phosphine oxides, H-phosphonates and their
4
are employed as electrophiles. Diversely substituted aryl
derivatives, as modular and air-stable preligands for cross-
9
,10
tosylates are readily available from the corresponding phenols
and inexpensive reagents. Therefore, and because of their
significantly increased stability toward hydrolysis when
compared to the corresponding triflates, they constitute
attractive substrates in cross-coupling reactions. However,
this superior stability translates into an inferior reactivity in
palladium-catalyzed coupling chemistry. Consequently, the
conversion of electronically unactivated aryl tosylates usually
requires electron-rich tertiary phosphines as stabilizing
coupling reactions using aryl and vinyl chlorides
or
1
1
fluorides, as well as direct arylation reactions employing
12
13-15
chlorides and tosylates.
In continuation of our studies,
we report on palladium-catalyzed Kumada cross-coupling
(5) Selected examples: (a) Hansen, A. L.; Ebran, J.-P.; Ahlquist, M.;
Norrby, P. O.; Skrydstrup, T. Angew. Chem., Int. Ed. 2006, DOI: 10.1002/
anie.200600442. (b) Nguyen, H. N.; Huang, X.; Buchwald, S. L. J. Am.
Chem. Soc. 2003, 125, 11818-11819. (c) Gelman, D.; Buchwald, S. L.
Angew. Chem., Int. Ed. 2003, 42, 5993-5996 and references cited herein.
(6) Roy, A. H.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 8704-
8705.
5
ligands. Specifically, generally applicable palladium-
(7) Limmert, M. E.; Roy, A. H.; Hartwig, J. F. J. Org. Chem. 2005, 70,
catalyzed cross-coupling reactions between organomagne-
9364-9370.
(8) For seminal work on the use of alkyl-substituted secondary phosphine
(
1) de Meijere, A., Diederich, F., Eds.; Metal-Catalyzed Cross-Coupling
Reactions, 2nd ed.; Wiley-VCH: Weinheim, 2004.
2) Beller, M., Bolm, C., Eds., Transition Metals for Organic Synthesis,
nd ed.; Wiley-VCH: Weinheim, 2004.
3) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176-
211.
4) Tsuji, J. Palladium Reagents and Catalysts, 2nd ed.; Wiley: Chich-
ester, 2004.
oxides, see: (a) Li, G. Y. Angew. Chem., Int. Ed. 2001, 40, 1513-1516.
Kumada coupling reactions: (b) Li, G. Y. J. Organomet. Chem. 2002, 653,
63-68. (c) Li, G. Y.; Marshall, W. J. Organometallics 2002, 21, 590-
591.
(9) Ackermann, L.; Born, R. Angew. Chem., Int. Ed. 2005, 44, 2444-
2447.
(
2
4
(
(
(10) Ackermann, L.; Gschrei, C. J.; Althammer, A.; Riederer, M. Chem.
Commun. 2006, 1419-1421.
1
0.1021/ol061116o CCC: $33.50
© 2006 American Chemical Society
Published on Web 07/04/2006