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

Abstract

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.

Transition-metal-free decarboxylative bromination of aromatic carboxylic acids

“…Our previous work on decarboxylative iodinations established a concerted decarboxylation-iodination process, via a 4-membered transition state, as a possible non-radical pathway for decarboxylative halogenations. 14 Following a similar protocol ( Fig. 1b ), our DFT study found a pathway for decarboxylative bromination proceeding through an analogous concerted decarboxylation-bromination transition state, TS-II .…”

“…We have recently reported a transition-metal-free decarboxylative iodination of aromatic acids. 14 The success of this procedure lies in the ability to prepare a variety of aryl iodides, simply by heating a benzoic acid in the presence of I 2 . We therefore questioned whether a similarly efficient and low-cost decarboxylative bromination could be developed.…”

Nickel‐Catalyzed Decarboxylative C–Si Bond Formation: A Regioselective Cross‐Coupling Between Trialkyl Silanes and α,β‐Unsaturated Carboxylic Acids

“…Gooßen and MacMillan most extensively explored the decarboxylative functionalizations for C–C bond formation . On the other hand, the decarboxylative C–X bond formation currently limited to the C–N, C–P, C–S, C–F, C–Br, and C–I bond creation. Particularly, the formation of C–Si bond, an analogues bond to the C–C bond, using decarboxylative functionalization has not been studied well .…”

Microwave-Assisted Silver-Catalyzed Protodecarboxylation and Decarboxylative Iodination of Aromatic Carboxylic Acids

“…As aromatic carboxylic acids are more widely available and cheaper, the successful decarboxylative iodination reaction will provide a reliable route for aryl iodides and has the potential of general application in organic synthesis. Very recently, an interesting transition metal-free decarboxylative iodination was reported by Larrosa [28], demonstrating that there is still room for improvement in this area. Scheme 2.…”