Mechanistic Insights
into the Cu(I)- and Cu(II)-Catalyzed
Cyclization of <i>o</i>‑Alkynylbenzaldehydes: The
Solvent DMF and Oxidation State of Copper Affect the Reaction Mechanism
- Publication date
- Publisher
Abstract
A computational
study with the BhandHLYP density functional is
conducted to elucidate the mechanisms of Cu(I)- and Cu(II)-catalyzed
reactions of <i>o</i>-alkynylbenzaldehydes with a nucleophile
(MeOH). Our calculations suggest the following. (a) The use of CuCl
as a catalyst deceases significantly the energy barrier and promotes
intramolecular cyclization. (b) Solvent DMF is critical in the stepwise
hydrogen-transport process involved in an intermolecular nucleophilic
addition because it can greatly reduce the free energy barrier of
the hydrogen-transfer process as a proton shuttle. In addition, we
find that substrate MeOH also plays a role similar to that of DMF
in the hydrogen-transport reaction. (c) The 6-endo product P1 is formed
exclusively using a catalytic system consisting of CuCl and DMF, whereas
a mixture of 6-endo product P1 and 5-exo product P2 in a ratio of
∼1:1 is produced using CuCl<sub>2</sub> and DMF as a catalytic
system. Our theoretical calculations reproduce the experimental results
very well. This study is expected to improve our understanding of
Cu(I)- and Cu(II)-catalyzed reactions involving Lewis base solvents
and to provide guidance for the future design of new catalysts and
new reactions