the Kumada reaction, path B cannot be the main catalytic cycle,
as such a mechanism would also imply (high) catalytic activity
of 1 in the Kumada reaction. The ground state energies of the
intermediates in path C are indeed reasonable to be traversed.
For example, dissociation of the chloride ligand from 1 and
formation of the cationic, T-shaped 14e- complex B is only
slightly endothermic (DE = +16.6 kcal mol-1). Furthermore, the
subsequent oxidative addition of phenyl bromide on the metal
center of B and formation of the cationic penta-coordinated
PdIV complex [(C10H13-1,3-(CH2P(C6H11)2)2)Pd(Br)(C6H5)]+ (C)
with the phenyl ligand positioned cis to the aliphatic unit of
the pincer core has a computed ground-state energy of +32.2
kcal mol-1, which lies only 15.6 kcal mol-1 above the sum of
the ground state energies of B and phenyl bromide and hence,
is indeed a possible intermediate in the catalytic cycle. This is in
contrast to its structural isomer C¢ (with the phenyl ligand in trans
position relative to the aliphatic pincer core), which has with a
computed energy of 41.0 kcal mol-1 a significantly higher ground-
state energy than C.29 The subsequent transmetalation of C (to
form D and bromo(phenyl)zinc) is only slightly endothermic. The
computed ground-state energy of the cationic, penta-coordinated
PdIV diphenyl complex [(C10H13-1,3-(CH2P(C6H11)2)2)Pd(C6H5)2]+
(D) and bromo(phenyl)zinc is +44.5 kcal mol-1 and hence, only
12.3 kcal mol-1 above the sum of the ground-state energies of
the reactants. The reductive elimination of biphenyl on the other
hand, is strongly exothermic (DE = -28.0 kcal mol-1) and closes
the catalytic cycle. The slight structural change for the reductive
elimination of biphenyl from D indicates a significantly smaller
energetic barrier (TSD/B) for the reductive elimination process
than for a second transmetallation and would provide a simple
and plausible explanation why homocoupling has only rarely been
observed as side-reaction.30
vations, such as the (rarely observed) formation of homocou-
pled side-products, the dramatic drop in activity when {2-
[(dimethylamino)methyl]phenyl}(phenyl)zinc instead of diarylz-
inc or chloro(aryl)zinc reagents were applied or why the Kumada
reaction is not promoted by 1. The DFT calculations fully support
the experimental results. Moreover, Pd–halide ◊ ◊ ◊ Zn adduct for-
mation is assumed to be crucial for the efficient biaryl formation
with 1 under Negishi reaction conditions and gained experimental
as well as computational support
Notes and references
1 (a) E.-I. Negishi, F. T. Luo, R. Frisbee and H. Matsushita, Heterocycles,
1982, 18, 117; (b) C. E. Tucker, T. N. Majid and P. Knochel, J. Am. Chem.
Soc., 1992, 114, 3983; (c) J. A. Miller and R. P. Farrell, Tetrahedron
Lett., 1998, 39, 7275; (d) T. Sakamoto, Y. Kondo, N. Murata and
H. Yamanaka, Tetrahedron Lett., 1992, 33, 5373; (e) T. Sakamoto, Y.
Kondo, N. Murata and H. Yamanaka, Tetrahedron, 1993, 49, 9713; (f) J.
E. Milne and S. L. Buchwald, J. Am. Chem. Soc., 2004, 126, 13028; (g) S.
P. Stanforth, Tetrahedron, 1998, 54, 263, and references therein; (h) J.
Hassan, M. Svignon, C. Gozzi, E. Schulz and M. Lemaire, Chem. Rev.,
2002, 102, 1359, and references therein.
2 (a) P. Knochel and R. D. Singer, Chem. Rev., 1993, 93, 2117; (b) A.
Boudier, L. O. Bromm, M. Lotz and P. Knochel, Angew. Chem., Int.
Ed., 2000, 39, 4414; (c) S. Q. Huo, Org. Lett., 2003, 5, 423; (d) C. Jubert
and P. Knochel, J. Org. Chem., 1992, 57, 5425; (e) R. Giovanni and P.
Knochel, J. Am. Chem. Soc., 1998, 120, 11186.
3 N. Miyaura, K. Yamada and A. Suzuki, Tetrahedron Lett., 1979, 20,
3437.
4 (a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457; (b) A.
Suzuki, in Metal-Catalyzed Cross-Coupling Reactions, ed. F. Diederich
and P. J. Stang, Wiley-VCH, Weinheim, 1998, chap. 2; (c) A. Suzuki, J.
Organomet. Chem., 1999, 576, 147; (d) S. R. Chemler, D. Trauner and S.
J. Danishefsky, Angew. Chem., Int. Ed., 2001, 40, 4544; (e) A. F. Littke
and G. C. Fu, Angew. Chem., Int. Ed., 2002, 41, 4176; N. Miyaura, Top.
Curr. Chem., 2002, 219, 11; (f) J. Hassan, M. Sevignon, C. Gozzi, E.
Schulz and M. Lemaire, Chem. Rev., 2002, 102, 1359; (g) S. Kotha, K.
Lahiri and D. Kashinath, Tetrahedron, 2002, 58, 9633; (h) F. Bellina,
A. Carpita and R. Rossi, Synthesis, 2004, 2419; (i) T. E. Barder, S.
D. Walker, J. R. Martinelli and S. L. Buchwald, J. Am. Chem. Soc.,
2005, 127, 4685; (j) K. C. Nicolaou, P. G. Bulger and D. Sarlah, Angew.
Chem., Int. Ed., 2005, 44, 4442; (k) N. T. S. Phan, M. V. D. Sluys and
C. W. Jones, Adv. Synth. Catal., 2006, 348, 609; (l) S. Nara, J. Martinez,
C.-G. Wermuth and I. Parrot, Synlett, 2006, 3185; (m) L. Ackermann,
H. K. Potukuchi, A. Althammer, R. Born and P. Mayer, Org. Lett.,
2010, 12, 1004.
Overall, the DFT calculations fully support the experimental
observations and strongly indicate that path C in Scheme 3 is the
only possible mechanism to be operative in the Negishi reaction
catalyzed by 1.
Conclusions
5 (a) S. Y. Cho and M. Shibasaki, Tetrahedron: Asymmetry, 1998, 9,
3751; (b) A. N. Cammidge and K. V. L. Cre´py, Chem. Commun., 2000,
1723; (c) J. Yin and S. L. Buchwald, J. Am. Chem. Soc., 2000, 122,
12051; (d) A. S. Castanet, F. Colobert, P. E. Broutin and M. Obringer,
Tetrahedron: Asymmetry, 2002, 13, 659; (e) A. Herrbach, A. Marinetti,
O. Baudoin, D. Guenard and F. Gueritte, J. Org. Chem., 2003, 68, 4897;
(f) A. N. Cammidge and K. V. L. Cre´py, Tetrahedron, 2004, 60, 4377;
(g) K. Mikami, T. Miyamoto and M. Hatano, Chem. Commun., 2004,
2082.
6 M. Kertesz, C. H. Choi and S. Yang, Chem. Rev., 2005, 105, 3448.
7 (a) A. Markham and K. L. Goa, Drugs, 1997, 54, 299; (b) R.
Capdeville, E. Buchdunger, J. Zimmermann and A. Matter, Nat. Rev.
Drug Discovery, 2002, 1, 493; (c) J. Boren, M. Cascante, S. Marin, B.
Comin-Anduix, J. J. Centelles, S. Lim, S. Bassilian, S. Ahmed, W. N.
Lee and L. G. Boros, J. Biol. Chem., 2001, 276, 37747.
In conclusion, complex 1 is an efficient, versatile and reliable
Negishi catalyst with high functional group tolerance, able to
quantitatively couple a large variety of electronically activated,
non-activated, deactivated and/or sterically hindered and func-
tionalized aryl bromides with various diarylzinc reagents in NMP
generally within less than 1 h at 100 ◦C in the presence of only
0.01 mol% of catalyst. All the experiments indicate a molecular
reaction mechanism to be operative with the cationic, T-shaped
14e- pincer complex [(C10H13-1,3-(CH2P(C6H11)2)2)Pd]+ (B) as key
intermediate, which undergoes oxidative addition with aryl bro-
mides to yield the penta-coordinated PdIV aryl bromide complexes
of type [(C10H13-1,3-(CH2P(C6H11)2)2)Pd(Br)(aryl¢)]+ (C). Subse-
quent transmetallation with Zn(aryl)2 result in the cationic diaryl
complexs of type [(C10H13-1,3-(CH2P(C6H11)2)2)Pd(aryl¢)(aryl)]+
(D), which reductively eliminates the coupling products, thereby
regenerating the catalyst. Halide re-coordination leads in the
formation of 1 and 3, respectively – the catalyst resting states.
Overall, even though some background reactivity via path B
cannot be excluded completely, path C is the only mechanism
that provides an explanation for all the experimental obser-
8 H. Tomori, J. M. Fox and S. L. Buchwald, J. Org. Chem., 2000, 65,
5334.
9 S. Lightowler and M. Hird, Chem. Mater., 2005, 17, 5538.
10 See, for example: (a) J. L. Bolliger, O. Blacque and C. M. Frech, Chem.–
Eur. J., 2008, 14, 7969; (b) J. L. Bolliger and C. M. Frech, Adv. Synth.
Catal., 2009, 351, 891; (c) J. L. Bolliger and C. M. Frech, Adv. Synth.
Catal., 2010, 352, 1075.
11 (a) J. L. Bolliger, O. Blacque and C. M. Frech, Angew. Chem., Int. Ed.,
2007, 46, 6514; (b) D. Benito-Garagorri, V. Bocokic, K. Mereiter and
K. Kirchner, Organometallics, 2006, 25, 3817; (c) M. Ohff, A. Ohff,
M. E. Van Der Boom and D. Milstein, J. Am. Chem. Soc., 1997, 119,
9002 | Dalton Trans., 2011, 40, 8996–9003
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