The ability to selectively functionalise a specific C-H bond is a long-standing challenge due to the ubiquity of such bonds in organic molecules. One of the most common approaches to overcome this ...obstacle consists of installing directing groups into substrates to direct the functionalisation towards the desired C-H bond, leaving behind the directing group in the molecule. Alternatively, carboxylic acids have been employed as traceless directing groups that are easily removed after carboxylic acid-directed installation of the desired functionality. This review focuses on the development of this concept and its application to organic synthesis during the last decade.
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.
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).
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.
Sulfonium salts are playing an increasingly significant role in contemporary organic synthesis. In particular, the generation of radicals from sulfonium salts is a fundamental process in Nature and ...has been the subject of investigation for over 50 years. However, general synthetic methods that use sulfonium salts as radical precursors are rare. The advent of photoredox catalysis has triggered an upsurge of interest in the radical chemistry of sulfonium salts and this review surveys recent applications of aryl‐ and alkylsulfonium salts in light‐mediated, radical C−C bond formation.
We report a transition-metal-free synthesis of benzofurans from benzothiophenes and phenols that exploits the unique reactivity of sulfoxides. Through a sequence involving an interrupted Pummerer ...reaction and 3,3 sigmatropic rearrangement, phenols can be combined with readily accessible yet synthetically unexplored benzothiophene S-oxides to provide C3-arylated benzofuran products. The products from this approach can undergo subsequent functionalization to gain access to a range of important benzofuran derivatives.
The beginning of the 21st century has seen tremendous growth in the field of decarboxylative activation. Benzoic acid derivatives are now recognised as atom‐economic alternatives to traditional ...cross‐coupling partners, and they also benefit from being inexpensive, readily available and shelf‐stable reagents. In this microreview we discuss recent developments in the coupling of benzoic acid derivatives either with an arene or with a second benzoic acid derivative, a process often termed decarboxylative oxidative cross‐coupling. These procedures offer great promise for the development of highly selective and atom‐economic cross‐couplings.
Developing efficient and selective routes for biaryl synthesis is of great interest. Decarboxylative oxidative coupling is appealing, because both substrate classes are readily available, and only CO2 and H2O are formed as side products. Furthermore, the carboxyl group offers a site for selective transformations. This review details decarboxylative oxidative coupling from 2008 to the present.
Trifluoromethyl sulfoxides are a new class of trifluoromethylthiolating reagent. The sulfoxides engage in metal‐free C−H trifluoromethylthiolation with a range of (hetero)arenes. The method is also ...applicable to the functionalization of important compound classes, such as ligand derivatives and polyaromatics, and in the late‐stage trifluoromethylthiolation of medicines and agrochemicals. The isolation and characterization of a sulfonium salt intermediate supports an interrupted Pummerer reaction mechanism.
May I interrupt? Taking advantage of the interrupted Pummerer reaction, trifluoromethyl sulfoxides engage in the metal‐free C−H trifluoromethylthiolation of (hetero)arenes, including drug molecules and natural products. This new class of trifluoromethylthiolating reagent exploits a new strategy for trifluoromethylthiolation in which sulfonium salts are assembled and selectively deconstructed.
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.
Copper-catalyzed functionalization of enynes Dherbassy, Quentin; Manna, Srimanta; Talbot, Fabien J. T ...
Chemical science (Cambridge),
10/2020, Letnik:
11, Številka:
42
Journal Article
Recenzirano
Odprti dostop
The copper-catalyzed functionalization of enyne derivatives has recently emerged as a powerful approach in contemporary synthesis. Enynes are versatile and readily accessible substrates that can ...undergo a variety of reactions to yield densely functionalized, enantioenriched products. In this perspective, we review copper-catalyzed transformations of enynes, such as boro- and hydrofunctionalizations, copper-mediated radical difunctionalizations, and cyclizations. Particular attention is given to the regiodivergent functionalization of 1,3-enynes, and the current mechanistic understanding of such processes.
The copper-catalyzed functionalization of enynes is a powerful approach to yield densely functionalized products. This review covers various transformations, such as boro- and hydrofunctionalizations, copper-mediated radical difunctionalizations, and cyclizations.
An efficient, enantio‐ and diastereoselective, copper‐catalyzed coupling of imines, 1,3‐enynes, and diborons is reported. The process shows broad substrate scope and delivers complex, chiral ...homopropargyl amines; useful building blocks on the way to biologically‐relevant compounds. In particular, functionalized homopropargyl amines bearing up to three contiguous stereocenters can be prepared in a single step.
The enantio‐ and diastereoselective, copper‐catalyzed three‐component coupling of imines, 1,3‐enynes, and diborons delivers complex, chiral homopropargyl amines; useful building blocks on the way to biologically‐ and medicinally‐relevant compounds. In particular, functionalized homopropargyl amines bearing up to three contiguous stereocenters can be prepared in a single step.
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