Radical Initiated Decarboxylation

Formation of organometallics by radical initiated decarboxylation is largely restricted to preparations of monoorganomercurials from mercuric carboxylates (see Section IV). These reactions are used as examples in the following discussion. 

Successful syntheses involving radical initiated decarboxylation are mainly limited to monoorganomercurials, where the method has extensive uses. Homolytic decarboxylation mechanisms have been discussed in Section II,C. 

Radical initiated decarboxylation appears to have considerable scope in organometallic synthesis, especially where the incoming radical is part of a coordinated ligand. 

Addition of P—H bonds to unsaturated systems also continues to be used as a route to heterocyclic systems. Thus base-catalysed cyclization of the phosphine (32) [prepared by the addition of methyl methacrylate (2 moles) to phenylphosphine], followed by subsequent hydrolysis and decarboxylation, affords the phosphorinanone (33). The phosphorinanone system is also directly accessible by the addition of phenylphosphine to divinyl ketones.28 The radical-initiated addition of phenylphosphine to dialkynyl systems (34) gives the heterocyclohexadienes (35).29 80 The stereochemistry of the addition of phenylphosphine to cyclo-octa-2,7-dienone to give... 

Decarboxylation.1 Esters of carboxylic acids are converted to the corresponding nor-hydrocarbons by reaction with n-Bu3SnH in the presence of AIBN as radical initiator. The reaction involves fragmentation to RC02 followed by loss of COz to give R-, which is reduced to RH. Yields arc in the range 60 90%. 

Many compounds will undergo dimerization reactions those containing thiols (e.g., disulfide formation) olefins, alcohols, and carboxylic acids (or other carbonyl chemistry e.g., aldol condensation reactions). Indoles have been shown to dimerize under acidic conditions. The dimerization is presumed to occur as shown in Figure 120 via protonation at C3 and nucleophilic attack of a second indole on C2. Phenols have been shown to dimerize under free radical initiated oxidative conditions, usually to ortho phenols. Nalidixic acid API undergoes dimerization under thermolysis conditions to decarboxylate and produce a dimeric structure (Fig. 121) (172). 

Bis(acyloxy)iodo]arenes 1 can serve as precursors to alkyl radicals 2 via decarboxylative radical decomposition initiated by irradiation with a mercury lamp (Hg-hv) or heating (Scheme 1) [3]. Generated under these conditions alkyl radicals 2 can be effectively trapped with the appropriate organic substrates affording products with a new C-C bond. The starting [bis(acyloxy)iodo]arenes 1 can be prepared in situ from the readily available [bis(trifluoroacetoxy)iodo]ben-zene or (diacetoxy)iodobenzene and a carboxylic acid. 

The initiation of the Barton Decarboxylation ( Bu3Sn-H -> Bu3Sn-) is effected with a radical initiator, and as with the Barton-McCombie Deoxygenation, the driving force for the reaction itself is the formation of the stable S-Sn bond. 

Stereochemistry in radical reactions for organic synthesis has not been studied very extensively, because mild or low temperature-promoted radical reaction methods are extremely limited and the stereoselectivity in radical reactions is generally rather poor. Recently, however, stereoselective organic synthesis with radical reactions has become popular, since mild radical reaction methods such as the Barton decarboxylation, Et3B-initiated Bu3SnH reaction, etc. have been developed. Normally, low temperature-initiated radical reactions induce high stereoselectivity. 

Decarboxylations . Decarboxylations of Hg carboxylates (RC02)2Hg lead to C—Hg-bonded compounds. Two methods are employed (a) UV- or free-radical-initiated reactions and (b) thermolysis ... 

III) Photochemlcally or Radical-Initiated Decarboxylations . Such decompositions of (RC02)2Hg compounds lead to RHg02CR derivatives and proceed via free-radical chain mechanisms ... 

Photoactivation of thiohydroxamic esters initiates a rapid decarboxylative radical rearrangement discovered by Barton [61] it has been used [62] in an application as a photolabile linker (Scheme 17.21). Coupling of indole-3-acetic acid 43 and... 

Free-radical polymerization results when a suitable alkene is heated with a radical initiator. For example, styrene polymerizes to polystyrene when it is heated to 100° C in the presence of benzoyl peroxide. This chain-growth polymerization is a free-radical chain reaction. Benzoyl peroxide cleaves when heated to give two carboxyl radicals, which quickly decarboxylate to give phenyl radicals. 

Reduction of acid chlorides with tripropyltin hydride in the presence of the radical initiator di-t-butyl peroxide has also been shown to furnish alkanes in moderate yield (equation 73). Carboxylic acids can also be decarboxylated via carboselenoic acid esters with TBTH in the presence of of AIBN... 

Itaconic acid and its anhydrid can only be homo- and copolymerized by radical initiation [1109-1114]. The polymeric acid is best prepared by hydrolysis of its poly anhydride [1109] because the free-radical polymerization of itaconic acid is accompanied by partial decarboxylation [1110,1111]. Mn values up to 900g/mol were reported for the polymeric acid [1109]. 

Some of the typical reactions that take place during an alkyd resin preparation and curing are (1) esterification, (2) alcoholysis, (3) ester interchange or transesterification, (4) etherification, (5) free radical addition reactions, (6) Diels-Alder reactions, (7) decarboxylations, and (8) polymerization via free radical initiation during curing (air-drying alkyds). 

Many new methods for the preparation of alkanes by reductive removal of functional groups have been reported during the year. Barton and his co-workers have presented a new radical decarboxylation for the conversion of carboxylic acids into hydrocarbons. Following esterification with /ran5-9-hydroxy-10-phenylthio-(or -10-chloro-)9,10-dihydrophenanthrene, a primary, secondary, or tertiary carboxylic acid is smoothly reduced under neutral conditions by tri-n-butylstannane and a radical initiator (e.g. Scheme 1). Formation of phenanthrene... 

Decarboxylation.—Selenoesters (RCOSePh), derived from carboxylic acids by way of the acid chloride, are transformed to the alkane (RH) on heating with tri-n-butyltin hydride in the presence of a radical initiator, whereas under photolytic conditions the corresponding aldehyde (RCHO) is the major product. Yields of decarboxylated product from various steroidal acids are high, but the conditions must be carefully controlled. The same degradation can be... 

C03 cluster grafted on a polyacrylate resin has been obtained through the free-radical-initiated polymerization of Go3(CO)9[C(CO)OCH2CH20(CO)CH=CH2], 420, with mixtures of methyl methacrylate and butyl acrylate. The Co3(CO)9 units remain fully intact in the thus-obtained films under ambient atmospheric conditions. [/t3-RC(0)OC]Co3(CO)9 (R = Ph, Bu) have been transformed to the corresponding (/t3-RC)Co3(CO)9 derivatives by silica-mediated decarboxylation. ... 

The difficulties inherent in the original Hunsdiecker reaction and its modifications stimulated the development of an additional halo-decarboxylation method that involves treatment of thiohydroxamic esters of carboxylic acids with BrCCls, ICH3 or CH2I2 in the presence of a radical initiator (Route 3, Barton reaction, Figure 10.23). 

The extent of decarboxylation primarily depends on temperature, pressure, and the stabihty of the incipient R- radical. The more stable the R- radical, the faster and more extensive the decarboxylation. With many diacyl peroxides, decarboxylation and oxygen—oxygen bond scission occur simultaneously in the transition state. Acyloxy radicals are known to form initially only from diacetyl peroxide and from dibenzoyl peroxides (because of the relative instabihties of the corresponding methyl and phenyl radicals formed upon decarboxylation). Diacyl peroxides derived from non-a-branched carboxyhc acids, eg, dilauroyl peroxide, may also initially form acyloxy radical pairs however, these acyloxy radicals decarboxylate very rapidly and the initiating radicals are expected to be alkyl radicals. Diacyl peroxides are also susceptible to induced decompositions ... 

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