Carbonylation of benzyl halides

Complexes of other metals are also capable of catalyzing useful carbonylation reactions under phase transfer conditions. For example, certain palladium(o) catalysts, like Co2(C0)g, can catalyze the carbonylation of benzylic halides to carboxylic acids. When applied to vinylic dibromides, unsaturated diacids or diynes were obtained, using Pd(diphos)2[diphos l,2-bis(diphenylphosphino)ethane] as the metal catalyst, benzyltriethylammonium chloride as the phase transfer agent, and t-amyl alcohol or benzene as the organic phase(18),... 

Carbonvlation of Benzyl Halides. Several organometallic reactions involving anionic species in an aqueous-organic two-phase reaction system have been effectively promoted by phase transfer catalysts(34). These include reactions of cobalt and iron complexes. A favorite model reaction is the carbonylation of benzyl halides using the cobalt tetracarbonyl anion catalyst. Numerous examples have appeared in the literature(35) on the preparation of phenylacetic acid using aqueous sodium hydroxide as the base and trialkylammonium salts (Equation 1). These reactions occur at low pressures of carbon monoxide and mild reaction temperatures. Early work on the carbonylation of alkyl halides required the use of sodium amalgam to generate the cobalt tetracarbonyl anion from the cobalt dimer(36). 

As the supported glycol catalysts worked better in promoting reactions in a single solvent system, we explored the direct carbonylation of benzyl halides using an alcohol solvent, base, and cobalt carbonyl. Our initial experiments concentrated on the reaction of benzyl bromide at room temperature and one atmosphere carbon monoxide. We chose sodium hydroxide as the base, methanol as the solvent, and looked at the product distribution. We were interested in the selectivity to ester and the reactivity of this system. The results are given in Table III. 

The transition metal-complex-catalyzed carbonylation of benzyl halides to yield phenylacetic acids is an extensively studied reaction [Eq. (7)]. 

The phase-transfer method has also been employed for the carbonylation of benzylic halides to carboxylic acids.477 The palladium(O) complexes [Pd(PPh3)4] (103), [Pd(diphos)2] (104) and [Pd(DBA)2] (105 DBA = dibenzylideneacetone) were used as catalysts. With (103) and (104) the carboxylic acid was the major product. Complex (105) gave little or none of the acid, the toluene and bibenzyl derivatives corresponding to the benzyl halide used being formed. Benzyl esters of the carboxylic acid were sometimes present as minor products. The reaction has been adapted to provide a new synthesis of anthranilic acid derivatives (equation 106).478 Tri-n-butylamine was used to neutralize the HBr formed. 

The catalytic carbonylation of benzylic halides to arylacetic acids has been improved by using two-phase systems under phase-transfer conditions [29]. Usually the reactions were performed with an excess of base in a biphasic system with a metal catalyst in the organic phase. As phase transfer catalysts surfactants are used, which appear to play an important transport function to move the cobalt carbonyl salt from the aqueous phase to the organic droplets (cf. Section 3.2.4). While the structure of the phase transfer co-catalyst was being studied it was observed that benzyltrialkylammonium salts were easily carbonylated. In some cases the yields of arylacetic acids are higher compared with the carbonylation of the corresponding benzyl halides [30]. 

The possibility of the carbonylation of organic halides under PTC conditions was demonstrated for the first time in 1976 [110], Benzyl chloride was transformed to phenylacetic acid in a xylene/aq. NaOH system containing a Pd° complex and a PT catalyst. Metal carbonyls are the most frequently used carbonylation catalysts. The effectiveness of Co2(CO)g for the PTC carbonylation of benzyl halides was discovered independently by two research groups [111, 112]. Under mild conditions, benzyl halides are converted into carboxylic acids (eq. (8)). 

The carbonylation of benzyl halides in t-BuOH, catalyzed by Pd(PPh3)2Cl2 and Et3N CH2PhCr, is a mild, efficient, one-pot route to /-butyl esters of arylacetic acids [131]. Similar reactions using benzyl halides, ethanol, CO, Bu4N I", and polymer-bound palladium chloride produce ethyl arylacetates [132]. 

Benzyl- and phenylacetyl derivatives of tetracarbonylcobalt(I) are believed to be important intermediates in the cobalt-catalyzed carbonylation of benzyl halides to phenylacetic acidi2twi and to phenylpyruvic acid ", carried out under phase transfer catalysis in the presence of catalytic amounts of a cobalt-carbonyl derivative. The carbonylation to phenylacetic acid proceeds as follows ... 

Again using PEGs as PT catalysts, the Alper group reinvestigated the carbonylation of benzyl halides in the presence of Co2(CO)8. They were able to characterize and investigate -benzyl, 3-benzyl, and ( -phenylacetyl) cobalt carbonyls as intermediates, and arrived at an elaborate mechanistic cycle [84],... 

Based on the palladium-catalyzed carbonylation of benzylic halides Sheldon and co-workers investigated the functionalization of 5-hydroxymethylfurfural (HMF) to 5-formylfuran-2-acetic acid (FFA) in aqueous medium in the presence of a water-soluble palladium/TPPTS catalyst (Scheme 3) [5], Here, the hydroxy group displays similar reactivity under acidic conditions compared with benzylic halides. 

Dichlorobis(triphenylphosphine)colMlt. Carbonylation of benzyl halides. ... 

Carbonylation and hydroformylation. With PEG as a PTC, COjCCO), mediates the carbonylation of benzylic halides. A more complex system is used in the transformation of propargylic alcohols into 2-alkylidenesuccinic acids (9 examples, 84-97%). Very similar results are obtained from the carbonylation of alkynyl ketones. "... 

It has been shown that in the Pd-catalyzed carbonylation of benzyl halides, the ligand attached to the metal has a great effect on the course of the reactionP t " i Althongh Pd-catalyzed carbonylation of benzyl halide is well documented, the preparation of tert-butyl ester has been describedP ... 

Cobaltcarbonyls are used for the carbonylation of benzyl halides or aromatic halides [74-76]. For example, as shown in eq. (17.31), benzylcarboxylic acid is prepared by the reaction of benzyl halide with carbon monoxide. The reaction mechanism is thought to be as follows at first the halogen atom of the halide is substituted by a cobalt atom and the Co-C bond formed is inserted into by a carbonyl. The phenylacetic acid is industrially produced by using this cobalt catalyst [77]. On aromatic halides, not only monocarbonylation but also double carbonylation is liable to proceed [74,75]. 

Carbonylation of Benzyl Halides. Benzyl halides can be converted into phenylacetic acids by reaction with Fe(CO)s. Phase-transfer catalysis is useful in this reaction. ... 

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