Chlorine Hunsdiecker reaction

Decarboxylation of the silver salts of carboxylic acids in the presence of bromine or chlorine, the Hunsdiecker reaction, often is useful for the synthesis of alkyl halides ... 

The classical Hunsdiecker reaction (equation 18), involving the reaction of silver caiboxylates widi halogens, and the various associated side reactions, has been reviewed several tunes. Optimum yields are obtain widi bromine, followed by chlorine. Iodine gives acceptable yields provid diat the correct stoichiometry of 1 1 is used. The reaction is most frequently carried out in tetrachloromediane at reflux. From a practical pmnt of view, one drawback is the difficulty encountered in the preparation of dry silver caiboxylates the reaction of silver oxide on the acyl chloride in tetrachloromediane at reflux has been employed to circumvent diis problem. Evidendy the use of molecular bromine limits die range of functional groups compatible widi die reaction the different reaction pathways followed by the silver salts of electron poor (equation 19) and electron rich (equation 20) aryl carboxyl s illustrate this point well. 

The preparation of chlorides by decarboxylation of carboxylic acids with lead tetraacetate and N-chlorosuccinimide as the chlorine donor in a 5 1 mixture of DM F and glacial acetic acid has been reported [71 a]. The reaction has been applied particularly often to the preparation of secondary and tertiary chlorides when the classic Hunsdiecker reaction gives low yields (Scheme 13.50) [71b]. This reaction proceeds by a radical pafhway. 

Another valuable alternative to the Hunsdiecker reaction is the Kochi modification,3 which employs a Pb(IV) reagent. It is a one-carbon oxidative degradation of carboxylic acids and is suitable for synthesis of secondary and tertiary chlorides as exemplified by the transformation of carboxylic acid 10 to cyclobutyl chloride (11) mediated by lead tetra-acetate (LTA).16 Further improvement of the Kochi modification employs LTA under milder conditions where N-chlorosuccinimide (NCS) is used as chlorinating agent and a mixture of DMF and HOAc as solvent.17... 

To prepare 4-iodooxazoles, Vedejs protocol with DMPU cosolvent allows for efficient synthesis. When DMF is used as the solvent, 2,4-unsubstituted oxazoles can be regioselectively brominated at the 4-position widi NBS on kilogram scale. Hunsdiecker reaction of a C4-carboxylic acid also provides the C4 bromide. With a substituted C2 position, Nicolaou and co-workers achieved chlorination of the C4 position using NCS to prepare an intermediate in the partial synthesis of diazonamide Similar to C2 trifloyloxazole synthesis, trapping of 4-oxazolones with triflic anhydride yields 4-trifloyloxazoles. These triflates, in contrast to 2- or 5-trifloyloxazoles are stable and can generally be utilized in cross-coupling reactions. 

The mechanism of a green Hunsdiecker reaction of cinnamic acids that produce (ii)-2-halostyrenes has been studied theoretically. The Hammett correlations and DFT calculations have shown that the rate-determining step is the electrophilic addition of a chlorine atom to the double bond. 

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