Hydrogenolysis Hydroxy esters

Imines can be hydrolyzed in quantitative yield by use of boric acid in ethanol under reflux [1]. Imines that are susceptible to intra- and intermolecular attack in the presence of other catalysts have been successfully hydrolyzed by use of boric acid [2], The conversion of isoxazolines into y3-hydroxy ketones and yS-hydroxy esters involves hydrogenolysis of the N-O bond and imine hydrolysis in a single step [3]. In the presence of boric acid, racemization is inhibited (Eq. 1) [3a]. 

Developed as a carboxyl protective group for peptide synthesis because of its stability to hydrogenolysis and acidic conditions, the acetol (hydroxy acetone) ester is prepared by DCC coupling (68-92% yield) of the acid with acetol. It is cleaved with TBAF in THF. ... 

This is by far the most versatile route to the synthesis of ester-substituted aziridines, especially as the benzhydryl group can easily be cleaved by hydrogenolysis. Wulff has applied this methodology to a short asymmetric synthesis of the antibiotic (-)-chloramphenicol in four steps from p-nitrobenzaldehyde (Scheme 1.34) [61]. In this case it was found that treatment of the aziridine 111 with excess dichloroacetic acid gave the hydroxy acetamide directly, so no separate deprotection step was required. 

During the preparation of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, the benzyl ester protecting group was removed by catalytic hydrogenolysis (Scheme 4.42). 

Hydrogenation temperatures can be lowered down to 125-150° when a large excess of the catalyst is used. Such a modification is especially useful in reductions of hydroxy and keto esters since the hydrogenolysis of diols or triols to alcohols is considerably lower and yields of the products range from 60% to 80%. The amounts of catalysts used in such experiments were up to 1.5 times the weight of the ester under the pressure of 350 atm [55]. 

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