Preferential reduction esters

When ethyl 4-methyl-2-methylthiopyrimidine-5-carboxylate or ethyl 2,4-dimethylpyrimidine-5-carboxylate was treated with lithium aluminum hydride at — 70°C, preferential reduction of the ester group occurred, yielding the 5-hydroxymethyl derivative rather than ring reduction.181... 

Alcohols from carboxylic acid esters Preferential reduction... 

The competition experiments [1] of a mixture of hexanal and 2-heptanone reveal the preferential reduction of aldehyde of over 85% (ktexanai/ iepatanone = 27) Cyclohexanone undergoes reduction at a faster rate than does cyclopentanone by a factor of 3.2. Cyclopentene is hydroborated with total exclusion of an ester, an acid, and an epoxide. Acid chlorides are reduced, quantitatively, without any significant attack on the esters (<2%). 

The Se-(4-methoxybenzyl)selenocysteine is obtained by reduction of selenocystine with NaBH4 and in situ reaction with 4-methoxybenzyl chloride. 7 The optimized procedure of Tanaka and Soda 32 is preferentially used for the synthesis of the starting selenocystine, which involves reaction of (1-chloroalanine with a 2.3-fold excess of disodium diselenide in aqueous solution at pH 9. Alternatively, the significantly less selenium demanding synthesis of Stocking et al. 33 is used for the preparation of expensive 77Se-selenocystine, this consists of the reaction of methyl (2R)-2-[(/ert-butoxycarbonyl)amino]-3-iodopropanoate with equivalent amounts of dilithium diselenide. Subsequent conversion of SeC(Mob) into the M -Fmoc derivative 7 and finally into the pentafluorophenyl ester 10 is performed following standard procedures. 

The best correlations were obtained with the values of a- constants generally applied to correlating chemical reactions which involve the phenolic oxygen.89 It is typical of the adverse influence of substituents that Eqs. (1) and (2) are significantly different in p values. The two nitro derivatives in both do not lie on the correlation lines. It was found that nitro-substituted aryl esters preferentially undergo alcoholysis and reduction.70... 

The Peterson reaction of the chlorovinyl-complex with ethyl trimethylsilylacetate provided the 11Z isomer preferentially (77%), and the 1 IE isomer as a secondary product (15%). The ester was transformed into the C 8 ketone (PhsSnCfy, BuLi, Et20, 79%). Reaction with (/Pr0)2P(0)CH2CN afforded the 1 lZ-retinonitrile in 73% yield. The complex was removed by CuC (72%) and DIBAL-H reduction led quantitatively to 1 lZ-retinal, Fig. (24). 

A very rare example of preferential photochemical reduction of an a-C-F bond rather than a //-chlorine occurs with chlorofluoropropanoates, in which this unusual selection in radical reactions is achieved by photochemical reduction.107 In oc.oc-difluoro esters 6 both C-F bonds can be reduced stepwise using hexamethylphosphoric triamide as the solvent and hydrogen donor.108 100... 

Ozonolysis is carried out preferentially in a methanol-dichloromethane mixed solvent system, followed by a reductive workup to produce the desired (3-keto ester 91, which is then further reacted to the 1-carbacephalosporin 89, providing a versatile and viable route to an important intermediate compound for monocyclic (3-lactam antibiotics. 

Fig. 13.42. Helmchen synthesis of enantiomerically pure a-alkylated carboxylic acids. The deprotonation of the propionic acid ester results in the "f "-enolate in the solvent THF and in the "Z"-enoLate in the solvent mixture THF/HHPA. In these projections, both enolates react preferentially from the front. The "f" -enolate results in a 97 3 mixture of 5- and fi-configured a-benzyl-propionic acid esters (X marks the chiral alkoxide group), while the "Z"-enolate results in a 5 95 mixture. Chromatographic separation and reduction of the C(=0)—Xc groups afford alcohol B with 100% ee from the " "-enolate and alcohol ent-B with 100% ee from the "Z"-enolate.

Fig. 14.53. Mechanism of the DIBAL reduction of carboxylic esters to aldehydes and further to alcohols. In nonpolar solvents the reaction stops with the formation of the tetrahedral intermediate A. During aqueous workup, A is converted into the aldehyde via the hemiacetal. In polar solvents, however, the tetrahedral intermediate A quickly decomposes forming the aldehyde via complex B. In the latter situation the aldehyde successfully competes with unreacted ester for the remaining DIBAL. The aldehyde is reduced preferentially, since the aldehyde is the stronger electrophile, and it is converted into the alcohol.

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