Chemical Science
Edge Article
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Conclusions
In summary, we carried out detailed mechanistic investigations
of the Pd(OAc)2-catalyzed C(sp3)–H g-arylation of amino acid
derivatives with aryl iodides. The results obtained, summarized
in Fig. 10, indicate that (i) in solution, the bimetallic Pd(II)
complex 5 is in equilibrium with an active monomeric species,
which represents the main species, (ii) the C–H activation step
is reversible, (iii) the bimetallic Pd(II) g-metalated complexes are
the resting states of the catalytic reaction and (iv) the C–H bond
cleavage step is likely not the rate determining step at least for
the tert-leucine derivative 4. In addition, the DFT calculations
explained the observed stereoselectivity in the case of the valine
derivative, for which arylation occurs exclusively at the pro-S
methyl group, and suggested that the reaction proceeds
through a Pd(II)/Pd(IV) mechanism via the oxidative addition of
an aryl iodide to a palladium(II) species followed by a reductive
elimination rate determining step. We hope that a greater
understanding of this transformation might contribute to the
design and development of novel reactions in this eld.
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Acknowledgements
´
Financial support from the Ministerio de Economıa y Com-
petitividad (MINECO, project CTQ2012-35790) and the Con-
´
´
sejerıa de Educacion de la Comunidad de Madrid (programme
AVANCAT; S2009/PPQ-1634) are gratefully acknowledged. We
thank Prof. Juan Carlos Carretero for helpful suggestions and
for laboratory facilities. We also thank the Centro de
´
´
Computacion Cientıca (UAM) for generous allocation of
computer time.
Notes and references
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3880 | Chem. Sci., 2014, 5, 3873–3882
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