Conspectus
Transition-metal-catalyzed cross-coupling reactions
represent one
of the most straightforward and efficient protocols to assemble two
different molecular motifs for the construction of carbon–carbon
or carbon–heteroatom bonds. Because of their importance and
wide applications in pharmaceuticals, agrochemicals, materials, etc.,
cross-coupling reactions have been well recognized in the 2010 Nobel
Prize in chemistry. However, in the classical transition-metal-catalyzed
cross-coupling reactions (e.g., the Suzuki–Miyaura, the Buchwald–Hartwig,
and the Ullmann cross-coupling reactions), organohalides, which mainly
stem from the nonrenewable fossil resources, are often utilized as
coupling partners with halide wastes being generated after the reactions.
To make cross-coupling reactions more sustainable, we initiated a
general research program by employing phenols and cyclohexa(e)nones
(the reduced forms of phenols) as pivotal feedstocks (coupling partners),
instead of the commonly used fossil-derived organohalides, for cross-coupling
reactions to build C–O, C–N, and C–C bonds. Phenols
(cyclohexa(e)nones) are widely available and can be obtained from
lignin biomass, highlighting their renewable and sustainable features.
Moreover, water is expected to be the only stoichiometric byproduct,
thus avoiding halide wastes.
Notably, the cross-coupling reactions
utilizing phenols/cyclohexa(e)nones
are not based on the traditional transition-metal-catalyzed “oxidative-addition
and reductive-elimination” mechanism, but via a novel “phenol-cyclohexanone”
redox couple. This new working mechanism opens up new horizons of
designing cross-coupling reactions via simple nucleophilic addition
of cyclohexanones along with aromatization processes, thereby simplifying
the design and avoiding laborious optimization of transition-metal
precursors (e.g., Pd, Ni, Cu, etc.), as well as ligands in classical
transition-metal-catalyzed cross-coupling reactions. Specifically,
in this Account, we will summarize and discuss our related research
work in the following three categories: “formal oxidative couplings
of cyclohexa(e)nones”, “formal reductive couplings of
phenols”, and “formal redox-neutral couplings of phenols”.
The successes of these research projects clearly demonstrated our
initial inspirations and rational designs to develop cross-coupling
reactions without the “conventional cross-coupling conditions”
by pushing the reaction frontiers from initial cyclohexanones, ultimately,
to the sustainable phenol targets.