Transition-Metal-Free Decarboxylative Iodination: New Routes for Decarboxylative Oxidative Cross-Couplings.

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.

Decarboxylative Suzuki-Miyaura coupling of (hetero)aromatic carboxylic acids using iodine as the terminal oxidant.

A novel methodology for the decarboxylative Suzuki-Miyaura-type coupling has been established. This process uses iodine or a bromine source as both the decarboxylation mediator and the terminal oxidant, thus avoiding the need for stoichiometric amounts of transition metal salts previously required. Our new protocol allows for the construction of valuable biaryl architectures through the coupling of (hetero)aromatic carboxylic acids with arylboronic acids. The scope of this decarboxylative Suzuki reaction has been greatly diversified, allowing for previously inaccessible non-ortho-substituted aromatic acids to undergo this transformation. The procedure also benefits from low catalyst loadings and the absence of stoichiometric transition metal additives.

Transition-metal-free decarboxylative bromination of aromatic carboxylic acids.

Methods for the conversion of aliphatic acids to alkyl halides have progressed significantly over the past century, however, the analogous decarboxylative bromination of aromatic acids has remained a longstanding challenge. The development of efficient methods for the synthesis of aryl bromides is of great importance as they are versatile reagents in synthesis and are present in many functional molecules. Herein we report a transition metal-free decarboxylative bromination of aromatic acids. The reaction is applicable to many electron-rich aromatic and heteroaromatic acids which have previously proved poor substrates for Hunsdiecker-type reactions. In addition, our preliminary mechanistic study suggests that radical intermediates are not involved in this reaction, which is in contrast to classical Hunsdiecker-type reactivity. Overall, the process demonstrates a useful method for producing valuable reagents from inexpensive and abundant starting materials.

The use of carboxylic acids as traceless directing groups for regioselective C-H bond functionalisation.

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.

Broad scope hydrofunctionalization of styrene derivatives using iron-catalyzed hydromagnesiation.

The highly regioselective iron-catalyzed formal hydrofunctionalization of styrene derivatives with a diverse range of electrophiles has been developed using a single, operationally simple hydromagnesiation procedure and only commercially available, bench-stable reagents. Using just 0.5 mol % FeCl2·4H2O and N,N,N',N'-tetramethylethylenediamine, hydromagnesiation and electrophilic trapping have been used to form new carbon-carbon bonds (13 examples) and carbon-heteroatom bonds (5 examples) including the products of formal cross-coupling reactions, hydroboration, hydroamination, hydrosilylation, and hydrofluorination.