ligand substitution at palladium between phosphine and carbene
is fairly general and that the metal carbene bond may be more
labile than previously thought. This would explain the ability of
complexes 1 and 4 to mediate amination and Sonagashira
reactions and could be consistent with a mechanism requiring
ligand dissociation prior to oxidative addition in the latter,14
although associative pathways for the ligand exchange reactions
in Scheme 2 cannot be ruled out at this stage.
In conclusion we have shown that two-coordinate palladium
bis-carbene and mixed carbene–phosphine complexes will
efficiently promote amination of aryl halides and demonstrated
an unexpected lability of the palladium–carbene bond. These
findings may be important in the design of new palladium–
carbene catalysts for organic synthesis.
We are grateful to AstraZeneca and EPSRC for support of
this project. We are grateful to Dr Abdul Sada for his
contribution.
Notes and references
‡ General procedure: KOBut (1.18 mmol) and complex 3 or 4 (0.016 mmol)
were weighed into an ampoule (fitted with a Youngs tap) in a glove-box.
Dioxane (10 ml) was added and then 4-chlorotoluene (0.79 mmol) and
amine (0.95 mmol) added and the mixture heated at 100 oC. The reaction
was allowed to cool to room temperature, the solvent removed and the
resulting mixture loaded directly onto a silica-gel plug and eluted using
ethyl acetate in hexane (20%). The solvent was evaporated and the product
was determined to be > 95% pure by spectroscopic and analytical
methods.
1 For reviews: (a) D. Bourissou, O. Guerret, P. Gabbai and G. Bertrand,
Chem. Rev., 2000, 100, 39; (b) A. J. Arduengo, Acc. Chem. Res., 1999,
32, 913; (c) M. Regitz, Angew. Chem., 1996, 35, 725.
2 For reviews: L. Jafarpour and S. P. Nolan, Adv. Org. Chem., 2001, 46,
181; T. Weskamp, V. P. W. Bohm and W. A. Herrmann, J. Organomet.
Chem., 2000, 600, 12; T. M. Trnka and R. H. Grubbs, Acc. Chem. Res.,
2001, 34, 18.
Scheme 2 R1 = But; R2 = C6H3Pri2-2,6.
3 For recent examples: A. Furstner and A. Leitner, Synlett, 2001, 290;
G. A. Grasa and S. P. Nolan, Org. Lett., 2001, 3, 119; H. M. Lee and
S. P. Nolan, Org. Lett., 2000, 2, 2053; J. Huang, G. Grasa and S. P.
Nolan, Org. Lett., 1999, 1, 1307.
4 For recent examples: D. J. Nielsen, K. J. Cavell, B. W. Skelton and A.
H. White, Organometallics, 2001, 20, 995; D. S. McGuinness, K. J.
Cavell and B. F. Yates, Chem. Commun., 2001, 355; T. Weskamp, V. P.
W. Bohm and W. A. Herrmann, J. Organomet. Chem., 1999, 585, 348;
A. A. D. Tulloch, A. A. Danopoulos, R. P. Tooze, S. M. Cafferkey, S.
Kleinhenz and M. B. Hursthouse, Chem. Commun., 2000, 1247; E.
Peris, J. A. Loch and R. H. Crabtree, Chem. Commun., 2001, 201.
5 J. C. Green, J. G. Scurr, P. L. Arnold and F. G. N. Cloke, Chem.
Commun., 1997, 1963.
6 V. P. W. Bohm, C. W. K. Gstottmayr, T. Weskamp and W. A.
Herrmann, J. Organomet. Chem., 2000, 595, 186.
7 P. L. Arnold, F. G. N. Cloke, T. Geldbach and P. B. Hitchcock,
Organometallics, 1999, 18, 3228.
8 S. Caddick, F. G. N. Cloke, G. K. B. Clentsmith, P. B. Hitchcock, D.
McKerrecher, L. R. Titcomb and M. R. V. Williams, J. Organomet.
Chem., 2001, 617, 635.
9 S. R. Stauffer, S. Lee, J. P. Stambuli, S. I. Hauck and J. F. Hartwig, Org.
Lett., 2000, 2, 1423.
excess of amine (4 equivalents), and proceeded in slightly lower
yield. In general the overall yields indicate that these are
extremely good catalysts for amination, however in contrast to
reported in situ methods, we were unable to promote these
reactions at room temperature.9
The ability of the sterically encumbered catalysts 1 and 4 to
undergo facile oxidative addition required for these amination
reactions is surprising, as is the similarity in catalytic behaviour
between 3 and 4. Given the currently accepted view that metal
N-heterocyclic carbene bonds are relatively strong compared to
metal phosphine bonds,1c we had expected that the mixed
species 3 would offer a superior class of pre-catalyst, as
phosphine dissociation to generate a mono-carbene palladium
species, followed by oxidative addition,10,13 should be more
facile than the required carbene dissociation in 4. However the
efficient behaviour of 4 as a pre-catalyst led us to conclude that
carbene dissociation from palladium may be more facile than
generally envisioned and this is borne out by further experi-
mentation (Scheme 2).
Treatment of 1 with P(o-tolyl)3 at 60 °C for 16 h resulted in
a 33% conversion to the mixed carbene–phosphine 2; prolonged
heating had no effect on the product ratio. Similar behaviour
was also observed in reaction of 1 with PCy3, to give 5, although
in this case the reaction proceeded to 100% completion in < 15
min at room temperature, and in the reaction of 4 with P(o-
tolyl)3, which gave the mixed complex 3 (28%). Ligand
redistribution reactions between 1 and [Pd{P(o-tolyl)3}2] and
between 4 and [Pd{P(o-tolyl)3}2] were also found to occur to
give 2 and 3 (92% and 28%, respectively). Finally we found that
treatment of complex 4 with free unsaturated carbene gave the
mixed bis-carbene complex 6 (67%); the latter could also be
obtained quantitatively by ligand redistribution between 1 and 4
at room temperature. These experiments demonstrate that
10 L. M. Alcaraz-Roman, J. F. Hartwig, A. L. Rheingold, L. M. Liable-
Sands and I. A. Guzei, J. Am. Chem. Soc., 2000, 122, 4618.
11 J. Huang, E. D. Stevens and S. P. Nolan, J. Am. Chem. Soc., 1999, 121,
2674; J. Huang, H. J. Shanz, E. D. Stevens and S. P. Nolan,
Organometallics, 1999, 18, 2370.
12 For examples: J. F. Hartwig, in Modern Amination Methods, ed. A.
Ricci, Wiley-VCH, Weinheim, 2000; B. H. Yang and S. L. Buchwald,
J. Organomet. Chem., 1999, 576, 125; J. F. Hartwig, Angew. Chem., Int
Ed., 1998, 37, 2047.
13 For a discussion of oxidative addition see: C. Amatore and F. Pfluger,
Organometallics, 1990, 9, 2276; C. Amatore, A. Jutand and A. Suarez,
J. Am. Chem. Soc., 1993, 115, 9531.
14 J. F. Hartwig and F. Paul, J. Am. Chem. Soc., 1995, 117, 5373; M. S.
Sanford, M. Ulman and R. H. Grubbs, J. Am. Chem. Soc., 2001, 123,
749.
Chem. Commun., 2001, 1388–1389
1389