Phenylacetic acid ethyl ester, carboxylation

To a stirred solution of 0.1 mmol (4R,VS)- and (45,l 5 )-4-(l -f rf-butoxycarbonyl-amino-2 -hydroxyethyl)-6-methyl-2-oxo-l,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester in 1 mL anhydrous CH2CI2 were added 29 mg (R)-Qf-methoxy-a -(trifluoro-methyl)phenylacetic acid (0.12 mmol), 25 mg 1,3-dicyclohexylcarbodiimide (0.12 mmol), and a catalytic amount of 4-A, A-(dimethylamino)pyridine. The mixture was stirred for an additional 12 h at room temperature, then concentrated. The residue was taken into EtOAc, washed with saturated aqueous NaHCOs and brine, dried over Na2S04, and concentrated. The residue was purified by preparative TLC, affording the corresponding Mosher ester in almost quantitative yield. 

The introduction of the trimethylsilyl chloride trapping technique" led to improved yields in the case of simple aliphatic esters. The initial silylated products are easily isolated and can be converted into the acyloins simply and in high yield. For simple aliphatic esters the yields are in the range 56-92%. Use of trimethylsilyl esters, rather than simple alkyl esters, leads to faster reactions, but lower yields.Substituted esters which have been successfully used in the newer procedure include ethyl 2-ethylhexanoate (83%), ethyl trimethylsilylacetate (90%)," ethyl 3-trimethylsilylpropionate (65%)," ethyl phenylacetate (48%)," ethyl 3-phenylpropionate (79%)" and 2-(2-methoxycarbonylethyl)-2-methyl-l,3-dioxolane derived from levulinic acid (65%)." In the case of ethyl adamantane-l-carboxylate the yield using the newer procedure is reported to be inferior to that using the earlier procedure. 

Titanium alkoxide is quite effective, presumably as an acid/base catalyst, at facilitating transesterification between esters and alcohols [511-513]. The reaction conditions are mild and relatively hindered alcohols can be used. Methyl phenylacetate has been transformed to other esters of relatively hindered alcohols under the influence of Ti(OEt)4 (Eq. 216) [514]. Ethyl (or methyl) esters of a variety of functionalized carboxylic acids could be converted into menthyl esters in good yields under titanium catalysis (Eq. 217) [514]. 

Reduction. The reagent is useful for reduction of carboxylic acid esters to primary alcohols. For example, the following esters have been reduced to the corresponding carbinols ethyl p-nitrobenzoate (96% yield), ethyl phenylacetate (90% yield), ethyl gly-cinate (70% yield). The reaction has some useful features Hydroxylic solvents (ethanol, water) can be used, the selectivity is higher than in the case of lithium aluminum hydride, and the reagent is nearly neutral. The reagent was found to be satisfactory for reduction of the dimethyl ester of 4,4 -dinitro-2,2 -diphenic acid (la) to the corresponding alcohol (lb, 51%yield).2... 

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