Pincer complex-catalyzed redox coupling of alkenes with lodonium salts via presumed palladium(IV) itermediates

Article abstract of DOI:10.1021/ol9010739

Palladium pincer complexes directly catalyze the redox coupling reactions of functionalized alkenes and iodonium salts. The catalytic process, which Is suitable for mild catalytic functionalization of allylic acetates and electron-rich alkenes, probably o

Full text of DOI:10.1021/ol9010739

ORGANIC
LETTERS
2009
Vol. 11, No. 13
2852-2854
Pincer Complex-Catalyzed Redox
Coupling of Alkenes with Iodonium
Salts via Presumed Palladium(IV)
Intermediates
Juhanes Aydin, Johanna M. Larsson, Nicklas Selander, and Ka´lma´n J. Szabo´*
Department of Organic Chemistry Arrhenius Laboratory, Stockholm UniVersity, Sweden
kalman@organ.su.se
Received May 15, 2009
ABSTRACT
Palladium pincer complexes directly catalyze the redox coupling reactions of functionalized alkenes and iodonium salts. The catalytic process,
which is suitable for mild catalytic functionalization of allylic acetates and electron-rich alkenes, probably occurs through Pd(IV) intermediates.
Due to the strong metal-ligand interactions, the oxidation of phosphine and amine ligands of the pincer complexes can be avoided in the
presented reactions.
Current development of catalytic procedures via palla-
dium(IV) intermediates represents one of the most important
recent innovations in transition metal catalysis.1,2 The most
attractive features2 of this approach involve increased
reactivity of the reductive elimination in Pd(IV) intermedi-
ates, increased chemoselectivity for the oxidative addition
to Pd(II) catalytic precursors, and the avoidance of unstable
Pd(0) intermediates.
problems have remained unresolved. Many ligand systems,
such as phosphines, employed in Pd(0)/Pd(II) processes are
easily oxidized under the reaction conditions used for
generating Pd(IV) intermediates, for example when iodonium
salts1a,3a are used as reagents. Besides, phosphines with
π-acceptor character deactivate oxidation of Pd(II) to Pd(IV)
species.
Therefore, catalytic transformations, aimed to proceed
through Pd(IV) intermediates, are usually restricted to the
use of simple palladium salts (such as acetates or chlorides)
as catalyst sources. This generates two major problems for
design of new processes via Pd(IV) intermediates: (i)
(1) (a) Canty, A. J.; Rodemann, T.; Ryan, J. H. AdVances in Organo-
metallic Chemistry; Elsevier: New York, 2008; Vol. 55, p 279. (b) Canty,
A. J. Acc. Chem. Res. 1992, 25, 83. (c) Deprez, N. R.; Sanford, M. S. Inorg.
Chem. 2007, 46, 1924.
(2) (a) Whitfield, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2007, 129,
15142. (b) Kalyani, D.; Deprez, N. R.; Desai, L. V.; Sanford, M. S. J. Am.
Chem. Soc. 2005, 127, 7330. (c) Daugulis, O.; Zaitsev, V. D. Angew. Chem.,
Int. Ed. 2005, 44, 4046. (d) Tong, X.; Beller, M.; Tse, M. K. J. Am. Chem.
Soc. 2007, 129, 4906. (e) Mun˜iz, K.; Ho¨velmann, C. H.; Streuff, J. J. Am.
Chem. Soc. 2008, 130, 763. (f) Liu, G.; Stahl, S. S. J. Am. Chem. Soc.
2006, 128, 7179. (g) Bressy, C.; Alberico, D.; Lautens, M. J. Am. Chem.
Soc. 2005, 127, 13148. (h) Alexanian, E. J.; Lee, C.; Sorensen, E. J. J. Am.
Chem. Soc. 2005, 127, 7690.
Although many excellent applications via proposed/
observed Pd(IV) intermediates have been reported,1,2 some
10.1021/ol9010739 CCC: $40.75
Published on Web 05/28/2009
 2009 American Chemical Society

application of chiral ligands with phosphines (or other easily
oxidizable species with high lying lone-pair orbitals), which
may dissociate from palladium under the catalytic process,
is strongly limited; and (ii) immobilization of palladium
catalysts requiring firm multidentate ligation is encumbered
by the easy oxidation of the applied ligand. To solve these
issues in Pd(II)/Pd(IV) chemistry, the application of pincer
complex (such as 1a-c, eq 1) catalysts4 offers a highly
attractive approach. Although similar ideas emerged over a
decade ago,4a,b,5a-c there has been an intensive debate on
the possibilities of generating Pd(IV) intermediates, when
pincer complexes are employed as direct catalysts. Several
studies5a-c indicate that aryl iodides are probably not
sufficiently reactive to maintain a Pd(II)/Pd(IV) catalytic
cycle based on pincer complexes.
Table 1. Pd-Catalyzed Coupling of Alkenes with Iodonium
Saltsa
Interestingly, however, van Koten6a and Canty6b have
shown that NCN complexes, such as 1b, undergo stoichio-
metric oxidative addition with iodonium salts3 affording
Pd(IV) pincer complexes (eq 2). We have now found that
palladium pincer complexes 1a,b can be employed as highly
active catalysts in Heck-type redox7 reactions of easily
available3b aryl-iodonium salts 2a-e with functionalized
alkenes (3a-k) in the presence of NaHCO3 in THF/CH3CN
(eq 1, Table 1).
The 31P NMR spectrum of the crude reaction mixture (see
Supporting Information) indicated that the pincer structure
of 1a remained intact after full conversion of the substrates.
A further confirmation that the pincer complex is the direct
catalyst of the reaction5a-c arises from the negative mercury-
drop test.5d When the reaction (entry 1) was conducted in
the presence of 150 equiv (per Pd) of elemental Hg, catalyst
poisoning was not observed, and the isolated yield was
identical to the yield of the corresponding process conducted
(3) (a) Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2008, 108, 5299. (b)
Bielawski, M.; Zhu, M.; Olofsson, B. AdV. Synth. Catal. 2007, 349, 2610.
(4) (a) Albrecht, M.; v. Koten, G. Angew. Chem., Int. Ed. 2001, 40,
3750. (b) v. d. Boom, M. E.; Milstein, D. Chem. ReV. 2003, 103, 1759. (c)
Szabo´, K. J. Synlett 2006, 811. (d) Benito-Garagorri, D.; Kirchner, K. Acc.
Chem. Res. 2008, 41, 201.
(5) (a) Sommer, W. J.; Yu, K.; Sears, J. S.; Ji, Y.; Zheng, X.; Davis,
R. J.; Sherrill, C. D.; Jones, C. W.; Weck, M. Organometallics 2005, 24,
4351. (b) Eberhard, M. R. Org. Lett. 2004, 6, 2125. (c) Phan, N. T. S.; v.
d. Sluys, M.; Jones, C. W. AdV. Synth. Catal. 2006, 348, 609. (d) Anton,
D. R.; Crabtree, R. H. Organometallics 1983, 2, 855.
(6) (a) Lagunas, M.-C.; Gossage, R. A.; Spek, A. L.; v. Koten, G.
Organometallics 1998, 17, 731. (b) Canty, A. J.; Rodemann, T.; Skelton,
B. W.; White, A. H. Organometallics 2006, 25, 3996.
(7) (a) Beletskaya, I. P.; Cheprakov, A. V. Chem. ReV. 2000, 100, 3009.
(b) Moriarty, R. M.; Epa, W. R.; Awasthi, A. K. J. Am. Chem. Soc. 1991,
113, 6315. (c) Zhu, M.; Song, Y.; Cao, Y. Synthesis 2007, 853. (d) Kang,
S.-K.; Lee, H.-W.; Jang, S.-B.; Kim, T.-H.; Pyun, S.-J. J. Org. Chem. 1996,
61, 2604. (e) Pan, D.; Chen, A.; Su, Y.; Zhou, W.; Li, S.; Jia, W.; Xiao, J.;
Liu, Q.; Zhang, L.; Jiao, N. Angew. Chem., Int. Ed. 2008, 47, 4729. (f)
Ohff, M.; Ohff, A.; Milstein, D. Chem. Commun. 1999, 357. (g) Kurihara,
J.; Sodboka, M.; Shibasaki, M. Chem. Pharm. Bull. 1994, 42, 2357. (h)
Liang, Y.; Luo, S.; Liu, C.; Wu, X.; Ma, Y. Tetrahedron 2000, 56, 2961.
(i) Sugioka, K; Uchiyama, M.; Suzuki, T.; Yamazaki, Y. Nippon Kagaku
Kaishi 1985, 527.
a Unless otherwise stated, 3 (0.3 mmol), 2 (0.2 mmol), NaHCO3 (0.2
mmol), and catalyst 1a,b,d (5 mol %) were dissolved in THF (A) or CH3CN
(B) (0.3 mL) and stirred at 50 °C. b Solvent. c Isolated yield. d Isolated yield
in the presence of 150 equiv of Hg. e 0.4 mmol of 3e was used. f Performed
at 65 °C.
Org. Lett., Vol. 11, No. 13, 2009
2853

without Hg (entry 1). Mercury itself did not show any
catalytic effect in the process. It is well established5a-c that
addition of Hg instantly terminates Heck reactions, when PCP
complexes (such as 1a) are not the direct catalysts but
dispensers of active Pd(0) species.
5b, instead of trans to the Pd-C(aryl) bond, as the latter is
destabilized by the trans influence of the hydride.
To demonstrate the synthetic potential of the Pd(II)/Pd(IV)-
based transformation, we concentrated on the preparation of
functionalized allylic acetates (4a-h) and aryl bromides.
These functionalities (allylic acetate and/or aryl bromide)
would easily undergo oxidative addition in a Pd(0)-catalyzed
transformation but remained unchanged in the presented
process. Unlike in standard7 Pd(0)-catalyzed Heck reactions,
alkenes with bulky electron-supplying groups (3e-h) react
readily and with high yields (entries 13-16). Furthermore,
diarylated byproducts were not detected.
It was found that Pd(OAc)2 1d also catalyzed the presented
coupling reactions (entries 3, 7, 11, 20, and 22). Interestingly,
the mercury-drop test5d with 1d was also negative (entry 3),
indicating that Pd(0) particles do not have a catalytic effect
in the process. This suggests that the mechanism of the pincer
complex and Pd(OAc)2-catalyzed reactions is similar, i.e.,
does not involve formation of catalytically active Pd(0)
species. As Pd(OAc)2 readily catalyzed the coupling reactions
of all types of substrates, such as allylic acetates (entries 3,
7, and 11), styrenes (entry 20), and even allyl sulfonate 3k
(entry 22), it can be regarded as an efficient, inexpensive
catalyst for synthesis of functionalized allylic compounds
and stilbene derivatives. However, application of pincer
complexes has some important potential advantages. The
trivalent phosphorus atom in 1a remained unchanged under
the coupling reaction due to the tight Pd-P coordination.
However, when PPh3 was added to the reaction catalyzed
by Pd(OAc)2 (entry 3) a complete oxidation of the phos-
phorus atom occurred. Furthermore, the above reactions
performed by pincer complexes give important mechanistic
insights as well. Pincer complexes are known5a-c to decom-
pose, when the metal atom is reduced to Pd(0), while
Pd(OAc)2 would be fully regenerated after reduction of
possibly occurring Pd(0) intermediates. Accordingly, our
findings that decomposition of the pincer complex catalysts
was not observed together with the negative Hg-poisoning
tests (entries 1 and 3) show that Pd(0) species are unlikely
to occur as catalytic intermediates indicating that the reactions
with 1a-d involve a Pd(II)/Pd(IV) redox cycle.
Our attempts to observe aryl-Pd(IV) complexes 5a or 6a
remained fruitless. Preliminary DFT modeling studies show
(eq 4) that oxidative addition of 1c (OAc analogue of OBz
complex 1b) proceeds through a considerably higher (by 13
kcal/mol) activation barrier to iodonium salt 2a than to 2f6b
(eq 2), while both reactions are highly exothermic. The
relatively high barrier, requiring elevated reaction temper-
ature, encumbers6b the observation of aryl-Pd(IV) com-
plexes (e.g., 5a, 6a). Unfortunately, iodonium salt 2f
decomposed under the applied catalytic conditions, and
therefore it could not be used as a substrate.
In summary, we have presented the first palladium pincer
complex catalyzed redox reaction, in which the integrity of
the complex is fully retained and the catalyst resists the Hg-
poisoning test. This process is suitable for mild arylation of
allylic acetates7e and electron-rich alkenes using easily
available3b iodonium salts. The presented method opens new
routes for application of PCP pincer complexes8 and other
palladacycles4 as efficient catalysts in redox transformations.
The main impact is expected for employment of Pd(II)/
Pd(IV)-based redox systems in asymmetric catalysis8c and
in immobilized/recyclable4a-c Pd catalysts.
Thus, the catalytic cycle (eq 3) of the PCP complex
catalyzed process is proposed to start with oxidative addition
of 2 to catalyst 1e affording Pd(IV) complex 5a. The next
step (5a f 5b) is carbo-palladation followed by ꢀ-hydride
elimination affording complex 5c, which subsequently
undergoes deprotonation by NaHCO3 regenerating catalyst
1e. The hydride probably enters trans to the X- ligand of
Acknowledgment. This work was mainly supported by
the Swedish Research Council (VR). Support from the Magn.
Bergvalls Stiftelse is also acknowledged.
(8) Synthesis and applications of 1a and analogues: (a) Bedford, R. B.;
Draper, S. M.; Scully, P. N.; Welch, S. L. New J. Chem. 2000, 24, 745. (b)
Solin, N.; Kjellgren, J.; Szabo´, K. J. J. Am. Chem. Soc. 2004, 126, 7026.
(c) Aydin, J.; Kumar, K. S.; Sayah, M. J.; Wallner, O. A.; Szabo´, K. J. J.
Org. Chem. 2007, 72, 4689. (d) Aydin, J.; Conrad, C. S.; Szabo´, K. J. Org.
Lett. 2008, 10, 5175. (e) Aydin, J.; Szabo´, K. J. Org. Lett. 2008, 10, 2881.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data are provided. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL9010739
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Org. Lett., Vol. 11, No. 13, 2009