Aryl-aryl cross-coupling constitutes one of the most widely used procedures for the synthesis of high-value materials, ranging from pharmaceuticals to organic electronics and conducting polymers. The assembly of (hetero)biaryl scaffolds generally requires multiple steps; coupling partners must be functionalized before the key bond-forming event is considered. Thus, the development of selective C-H arylation processes in arenes, that side-step the need for prefunctionalized partners, is crucial for streamlining the construction of these key architectures. Here we report an expedient, one-pot assembly of (hetero)biaryl motifs using photocatalysis and two non-prefunctionalized arene partners. The approach is underpinned by the functionalization of a C-H bond in an arene coupling partner using the interrupted Pummerer reaction. A unique pairing of the organic photoredox catalyst and the intermediate dibenzothiophenium salts enables highly selective reduction in the presence of sensitive functionalities. The utility of the metal-free, one-pot strategy is exemplified by the synthesis of a bioactive natural product and the modification of complex molecules of societal importance.
The catalytic conversion of chemical feedstocks into products of medicinal and agricultural value is a key theme across modern synthetic chemistry. As 1,3-dienes are readily available from industrial cracking processes, there is great interest in the development of sustainable methods for the functionalization of these simple molecules. Although initial developments in this field have required precious-transition-metal catalysts, there has been a push toward the use of inexpensive, nontoxic, and more abundant copper catalysts to promote functionalization. This Perspective covers the many developments in the area of copper-catalyzed functionalization of 1,3-dienes, in particular hydrofunctionalization, borofunctionalization, and difunctionalization (e.g., diamination).
This feature article focuses on the use of carboxylic acids as traceless directing groups and the application of this concept to achieve regiochemical control in organic chemistry.
Constructing products of high synthetic
value from inexpensive and abundant starting materials is of great
importance. Aryl iodides are essential building blocks for the synthesis
of functional molecules, and efficient methods for their synthesis
from chemical feedstocks are highly sought after. Here we report a
low-cost decarboxylative iodination that occurs simply
from readily available benzoic acids and I2. The reaction
is scalable and the scope and robustness of the reaction is thoroughly
examined. Mechanistic studies suggest that this reaction does not
proceed via a radical mechanism, which is in contrast to classical
Hunsdiecker-type decarboxylative halogenations. In addition,
DFT studies allow comparisons to be made between our procedure and
current transition-metal-catalyzed decarboxylations. The utility
of this procedure is demonstrated in its application to oxidative
cross-couplings of aromatics via decarboxylative/C–H
or double decarboxylative activations that use I2 as the terminal oxidant. This strategy allows the preparation of
biaryls previously inaccessible via decarboxylative methods
and holds other advantages over existing decarboxylative oxidative
couplings, as stoichiometric transition metals are avoided.
Although
the ruthenium-catalyzed C–H arylation of arenes
bearing directing groups with haloarenes is well-known, this process
has never been achieved in the absence of directing groups. We report
the first example of such a process and show that unexpectedly the
reaction only takes place in the presence of catalytic amounts of
a benzoic acid. Furthermore, contrary to other transition metals,
the arylation site selectivity is governed by both electronic and
steric factors. Stoichiometric and NMR mechanistic studies support
a catalytic cycle that involves a well-defined η6-arene-ligand-free Ru(II) catalyst. Indeed, upon initial pivalate-assisted
C–H activation, the aryl-Ru(II) intermediate generated is able
to react with an aryl bromide coupling partner only in the presence
of a benzoate additive. In contrast, directing-group-containing substrates
(such as 2-phenylpyridine) do not require a benzoate additive. Deuterium
labeling and kinetic isotope effect experiments indicate that C–H
activation is both reversible and kinetically significant. Computational
studies support a concerted metalation–deprotonation (CMD)-type
ruthenation mode and shed light on the unusual arylation regioselectivity.
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