Hunsdiecker oxidative decarboxylation

Silver-mediated C—X bond formation was known for many years as the Hunsdiecker reaction, in which substrates bearing carboxylic acids are oxidatively decarboxylated to give alkyl halides in the presence of halogens (142). If olefins are used with silver benzoate and I2, the Prevost reaction occurs to yield diols (143). 

Oxidative decarboxylation of optically active l-methyl-2,2-diphenylcyclopropanecarboxylic acid (10) with lead tetraacetate in the presence of iodine leads to racemized 1-iodo-l-methy 1-2,2-diphenylcyclopropane (11) in 45% yield. Subjecting 10 to the Cristol-Firth modification of the Hunsdiecker reaction (bromine and mercuric oxide in carbon tetrachloride) leads to racemic 1-bromo-l-methyl-2,2-diphenylcyclopropane (12) however, the yield is poor (5 /o). ... 

The Hunsdiecker process has the disadvantage of requiring dry silver salts. As a consequence, other methods have been sought, and it has been found that some carboxyhc acids undergo oxidative decarboxylation on formation of mercury (Hg), lead (Pb), or copper (Cu) salts. For example, cyclopropane carboxyhc acid, on treatment with bromine (Br2) in the presence of red mercury(II) oxide (HgO), yields hydrogen bromide (HBr), carbon dioxide (CO2), and bromcxyclopropane (cyclopropyl bromide) as shown in Equation 9.84. 

A related method for conversion of carboxylic acids to bromides with decarboxylation is the Hunsdiecker reaction.276 The usual method for carrying out this transformation involves heating the carboxylic acid with mercuric oxide and bromine. 

The decarboxylation of carboxylic acid in the presence of a nucleophile is a classical reaction known as the Hunsdiecker reaction. Such reactions can be carried out sometimes in aqueous conditions. Man-ganese(II) acetate catalyzed the reaction of a, 3-unsaturated aromatic carboxylic acids with NBS (1 and 2 equiv) in MeCN/water to afford haloalkenes and a-(dibromomethyl)benzenemethanols, respectively (Eq. 9.15).32 Decarboxylation of free carboxylic acids catalyzed by Pd/C under hydrothermal water (250° C/4 MPa) gave the corresponding hydrocarbons (Eq. 9.16).33 Under the hydrothermal conditions of deuterium oxide, decarbonylative deuteration was observed to give fully deuterated hydrocarbons from carboxylic acids or aldehydes. 

Generally, potassium persulfate in the presence of Ag+ is used for the Hunsdiecker type radical decarboxylation of carboxylic acids in water. (Bu4N+)2S208 (P) is soluble in THF, and a sulfate anion radical [i] is formed under refluxing conditions. Thus, refluxing treatment of / (tetrabutylammonium) persulfate (P) in the presence of alcohol in THF provides tetrahydrofuryl-protected alcohol (4), through the abstraction of a-H from THF by sulfate anion radical [I], followed by oxidation to a tetrahydrofuryl cation, as shown in eq.12.3 [28]. 

The process of substitution undertaken on carboxylic acids and the derivatives of carboxylic acids (anhydrides, acid halides, esters, amides, and nitriles) generally involves a series of replacement processes. Thus, individually, substitution may involve replacement of (a) the proton attached to oxygen of the -OH group (i.e., ionization of the acid) (b) the hydroxyl (-OH) portion of the carboxylic acid (or derivative) (e.g., esterification) (c) the carbonyl oxygen and the hydroxyl (-OH) (e.g., orthoester formation, vide infra) (d) the entire carboxylic acid functionality (e.g., the Hunsdiecker reaction, already discussed Scheme 9.101) and the decarboxylation of orotic acid (as orotidine monophosphate) to uracil (as uridine monophosphate)—catalyzed by the enzyme orotidine monophosphate decarboxylase (Scheme 9.115) or (e) the protons (if any) on the carbon to which the carboxylic acid functional group is attached (e.g., the Dieckman cycUzation, already discussed earlier, c Equation 9.91). Indeed, processes already discussed (i.e., reduction and oxidation) have also accomplished some of these ends. Some additional substitutions for the carboxylic acid group itself are presented in Table 9.6, while other substitutions for derivatives of carboxylic acids are shown in Tables 9.7-9.10 and discussed subsequently. 

If the silver salt of a carboxylic acid is treated with bromine, the salt decarboxylates and a bromoal-kane forms. This process is called the Hunsdiecker reaction. The decarboxylation reaction can also be carried out using the carboxylic acid and mercury(II) oxide. 

The first enantiospecific route to this class of natural products was reported by Williard and de Laszlo (Scheme 43.47). The route started with the a,a-dichlorination of aldehyde 298 with enamine formation followed by chlorination with A-chlorosuccinimide (NCS) to afford 299 in 72% yield. The subsequent oxidation of aldehyde 299 with KMn04, followed by Kochi-Hunsdiecker decarboxylative chlorination of resultant carboxylic acid 300, afforded trichloromethyl ester 301 in 77% yield. Ester 301 was divergently converted into aldehyde 302 and carboxylic acid 303, both of which were mixed with thiazol-2-ylmethyl isocyanide and MeNH2 to promote Ugi condensation to yield (+)-demethyldysidenin 304, an enantiomer of the natural product, along with the C5-epiner. This work has led to the... 

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