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Computational Study on Gold-Catalyzed Cascade Reactions of 1,4-Diynes and Pyrroles: Mechanism, Regioselectivity, Role of Catalyst, and Effects of Substituent and Solvent
journal contribution
posted on 2018-06-12, 11:57 authored by Ran Fang, Lin Zhou, Peng-Cheng Tu, Alexander M. Kirillov, Lizi YangThis study is devoted
to a theoretical investigation of the mechanism,
regioselectivity, role of catalyst, and effect of substituent and
solvent in the Au-catalyzed cascade reaction between 1,4-diynes and
pyrroles. Density functional theory (DFT) calculations indicate that
this reaction comprises four principal stages: (1) formation of different
intermediates through the first intermolecular hydroarylation, (2)
1,3-H transfer to give the enyne intermediates, (3) a second intermolecular
hydroarylation, and (4) a second proton transfer along with Au(I)
catalyst regeneration and final product formation. In addition, the
computational results suggest that the first regioselectivity is determined
by the electronic effects of the reagents. However, the torsional
strains within the transition structures (intramolecular cyclization)
and electronic effects of enyne intermediates would account for the
second regioselectivity. A global reactivity index (GRI) analysis
for different gold catalysts (namely, IPrAu+, PPh3Au+, BrettPhosAu+, and JohnPhosAu+) shows the important role of the catalyst in enhancing the electrophilicity
of 1,4-diynes, thus making possible a nucleophilic attack between
the 2-position of pyrrole and the C1 or C2 position
of the 1,4-diyne substrate. In addition, the effects of substituent
and solvent were also analyzed in detail and discussed. Apart from
being in good agreement with experimental data, the obtained DFT results
also provide a notable contribution toward an understanding of the
reaction mechanism.