Transition-Metal-Free Hunsdiecker Reaction of Electron-Rich Arenecarboxylic Acids and Aryl Aldehydes in Water

Abstract

An I 2 O 5 -mediated decarboxylative and decarbonylative bromination/iodination of electron-rich arenecarboxylic acids and aryl aldehydes by using KBr/KI as the halogen source in water has been developed. This scalable, low-cost, and transition-metal-free halogenation allows convenient access to aryl bromide and iodide under mild conditions. Direct decarboxylative halogenation of carboxylic acid represents one of the most useful strategies for the preparation of halides in synthetic organic chemistry, which is known as the Hunsdiecker reaction. 1-3 To overcome the limitations of the Hunsdiecker reaction, various methods had been developed by Cristol, 4 Barton, 5 and Kochi 6 et al. during the past decades. These pioneering studies along with their modifications provide helpful strategies for the synthesis of alkyl halides, however, most of these systems suffer from previous preparation of carboxylic metal salts and/or esters, overloading of heavy metal salts, and harsh reaction conditions. Very recently, Li and co-workers reported a very efficient silver(I)-catalyzed decarboxylative chlorination and fluorination of aliphatic carboxylic acids. 7 However, aryl carboxylic acids gave no desired products in this system. In 2011, Gandelman and co-workers developed an iododecarboxylation of carboxylic acids by using 1,3-diiodo-5,5-dimethylhydantoin under irradiation conditions. 8 Additionally, a decarboxylative halogenation of electron-rich aryl carboxylic acids by using hypervalent iodine(III)-LiX in fluoroalcohol media was explored by Miki et al. 9 Although these transition-metal-free Hunsdiecker reactions have made the decarboxylative halogenation easier than ever before, challenging problems such as using relatively high-cost halogen sources and oxidant, requirement of fluoroalcohol as the effective medium, and difficulty of large-scale production remain to be addressed so far. To address these challenges, we began to reason that single-electron oxidation of simple halogen anion (e.g., Br -, I -) by a low-cost and nonmetal inorganic oxidant would lead to efficient decarboxylative halogenation of carboxylic acids. The key problem of this strategy lies in finding a proper single-electron oxidant. As our continuous studies on exploring green oxidation systems using more safe and environmentally benign oxidants such as molecular oxygen, HIO 3 (iodic acid, IA), and its anhydride I 2 O 5 (iodine pentoxide, IP), we find that IA and IP can act as safe and reliable single-electron oxidative surrogates for organic hypervalent iodines in several cases. 10 Although IA and IP are very rarely employed in organic synthesis, 11 they are extensively applied in industry due to their particular stability even under high temperature. 12 In order to realize a transition-metal-free decarboxylative halogenation, we hypothesize that oxidation of KBr/KI by IA and/or IP would lead to an efficient Hunsdiecker reaction. Fortunately, we successfully accomplished a safe, green, and scalable decarboxylative bromination and iodination of electron-...

Decarboxylation‐Initiated Intermolecular Carbon‐Heteroatom Bond Formation

“…disclosed an I 2 O 5 −KX (X=Br, I) combination, which permits halogenations in water (Scheme 9). [171] Another effective system consists of sodium persulfate (Na 2 S 2 O 8 ) as the oxidant and N ‐halosuccinimide (NXS) (X=Cl, Br, I) as halogen sources [172] . Although both protocols proceed under mild condition, they are limited to benzoic acids bearing at least two electron‐donating groups (−OR, −NH 2 ), and lead to dihaloarenes as byproducts as a result of an additional electrophilic aromatic substitution (S E Ar) in the activated aromatic ring (Scheme 9B).…”

Decarboxylative Halogenation of Organic Compounds

“…Liu et al demonstrated the applicability of the iodine pentoxide-KX system for the preparation of mono-, di-, and even trihalides in the presence of various methoxy or amino-groups (Scheme ). However, additional electron-withdrawing groups, such as Cl and Br, reduced the product yield or made the reaction impossible, as was observed for 2,6-dimethoxy-3-bromobenzoic acid ( 423 ).…”

Palladium‐Catalyzed Decarbonylative Iodination of Aryl Carboxylic Acids Enabled by Ligand‐Assisted Halide Exchange

“…[ 22 , 23 , 24 ] However, current reactions still exhibit several drawbacks: they either require preactivation of the carboxylic acid, [23b] stoichiometric amounts of transition metal,[ 23c , 23d ] or a tailor‐made Ir‐photocatalyst for the installation of the carbon−iodine bond. [ 23b , 23e ] In addition, several reports show limited substrate scope,[ 23f , 23g ] or afford the desired aryl iodides in only modest yields. [23h] Larrosa et al.…”