Communications
hydrazines was not observed in any case, which suggests that
B is a short-lived intermediate. Preliminary mechanistic NMR
studies on the reaction of 1 f with 10 equivalents of aryl
boronic acid under the catalysis conditions (308C, c = 0.2m) in
tetrachloroethane show a clean conversion to compound 3h
within 2h. The intermediate complex B was not observed
under these conditions, which again suggests that the reduc-
tive elimination of 3 from B proceeds extremely rapidly.[15]
The palladadiaziridine is finally regenerated from com-
plex C through coordination of free azodicarboxylate, which
apart from its role as precursor to the hydrazide product,
serves as a reoxidant. This use represents a significant step
forward in comparison to related coupling reactions such as
the oxidative Heck reaction between boronic acids and
alkenes, in which the reoxidation with molecular oxidant
requires further additives.[16]
In summary, we have described a selective protocol, which
is mild and side-product free, for the coupling of aryl boronic
acids and azo compounds to provide N-aryl hydrazines. The
key step of the catalysis consists of the first general reductive
carbon–nitrogen bond formation from palladium amidate
complexes. The course of this reaction strongly depends on
the nature of the ligand, and phenanthroline-type ligands are
presently unchallenged. We expect that this class of ligands
will find broader applicability in the direct functionalization
of amides and are currently being investigated in potential
reactions.
Scheme 2. Buchwald–Hartwig coupling with product 3n.
dominating role of the nature of the chelating ligand on the
course of the coupling reaction and enables a defined
differentiation of reactivity.
A catalytic cycle for the mechanistic understanding of this
À
new C N bond formation from azodicarboxylates and aryl
boronic acids is suggested in Figure 1a. The reaction is
initiated by aryl transfer from the boronic acid to the
palladium center with concomitant opening of the pallada-
diaziridine, thus leading to the formation of complex B. A
reductive elimination of the monoarylated hydrazine 3 from
the amidato complex B generates the corresponding palla-
dium(0) complex C. The spontaneous character of this
process is of particular significance in view of the mentioned
difficulties in sp2-carbon–amide coupling reactions in tradi-
tional Buchwald–Hartwig reactions. In addition, no hydra-
zine-exchange processes take place at stage B under the
chosen conditions, since the formation of N,N’-bisarylated
Received: January 22, 2007
Revised: May 15, 2007
Published online: July 19, 2007
Keywords: amides · aryl boronic acids · coupling reactions ·
.
hydrazines · palladium
[1] For reviews, see: a) J. Tsuji, Palladium Reagents and Catalysts,
Wiley, New York, 2004; b) Handbook of Organopalladium
Chemistryfor Organic Snythesis
(Ed.: E.-i. Negishi), Wiley,
New York, 2002; c) Top. Curr. Chem. 2002, 219 (Ed.: N.
Miyaura); d) Transition Metals for Organic Synthesis: Building
Blocks and Fine Chemicals (Eds.: M. Beller, C. Bolm), Wiley-
VCH, Weinheim, 2nd ed., 2004.
[2] a) A. R. Murci, S. L. Buchwald, Top. Curr. Chem. 2002, 219, 133;
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[3] For reviews, see: a) J. F. Hartwig, Synlett 2006, 12 83; b) S. L.
Buchwald, C. Mauger, G. Mignani, U. Scholz, Adv. Synth. Catal.
2006, 348, 23; c) J. P. Wolfe, S. Wagaw, J. F. Marcoux, S. L.
Buchwald, Acc. Chem. Res. 1998, 31, 805.
[4] For an extensive mechanistic investigation, see: S. Shekhar, P.
Rynberg, J. F. Hartwig, J. S. Mathew, D. G. Blackmond, E. R.
Strieter, S. L. Buchwald, J. Am. Chem. Soc. 2006, 128, 3584.
[5] For a review, see: J. Barluenga, C. ValdØs, Chem. Commun. 2005,
4891.
[6] a) J. Yin, S. L. Buchwald, J. Am. Chem. Soc. 2002, 124, 6043; b) J.
Yin, S. L. Buchwald, Org. Lett. 2000, 2, 1101.
Figure 1. a) Catalytic cycle for palladium-catalyzed coupling between
aryl boronic acids and azodicarboxylates, and b) monitoring by NMR
spectroscopy of the standard reaction of 1 f to give 3h.
[7] K.-i. Fujita, M. Yamashita, F. Puschmann, M. Martinez Alvarez-
Falcon, C. D. Incarvito, J. F. Hartwig, J. Am. Chem. Soc. 2006,
128, 9044.
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Angew. Chem. Int. Ed. 2007, 46, 6350 –6353