Reduction of esters

Esters can also be reduced by the addition of hydrogen in the presence of oxides of copper and chromium known as copper chromide. Reduction can also be carried out by LiAlH4, though this method is very expensive. 

The direct reduction of a carboxylic acid to an alcohol is very difficult to carry out, so the acid can be first esterified and then reduced to the alcohol. 

Esters react with two equivalents of a Grignard reagent to give tertiary alcohols. The reaction proceeds by irreversible nucleophilic attack of the Grignard reagent on the ester carbonyl group. The initial product, a ketone, reacts further in the usual way to give the tertiary alcohol. 

This method is useful for making tertiary alcohols in which at least two of three alkyl groups attached to the hydroxyl-bearing carbon atom are identical. 

PROBLEM 10.21 Using eq. 10.27 as a guide, write the structure of the tertiary alcohol that is obtained from 

Esters can be reduced to primary alcohols by lithium aluminum hydride (LiAlH4). 

The mechanism is similar to the hydride reduction of aldehydes and ketones (eq. 9.33). 

The reduction of an ester either by lithium aluminum hydride or by catalytic hydrogenation at high temperatures under a high pressure of hydrogen yields a primary alcohol. Any aldehyde intermediate that forms is much more easily reduced than the ester. Diisobutylaluminum hydride, [(CH3)2CHCH2)]2A1H, is less reactive than lithium aluminum hydride. At—78 °C in toluene, the reagent, known as DIBAL, reduces esters to aldehydes. 

The aldehyde forms in two steps. First, addition of aluminum to the carbonyl oxygen atom and hydrogen to the carbonyl carbon atom forms an aluminate. Subsequent hydrolysis yields a hemiac-etal, which decomposes to give the aldehyde. The hemiacetal is not converted to an aldehyde in the presence of DIBAL, so it is not reduced to an alcohol. 

---

Bouveault-Blanc reduction The reduction of esters to alcohols by nascent hydrogen gen-... 

Reduction of esters of monobasic acids with sodium and absolute ethyl alcohol (method of Bouveault and Blanc), for example ... 

The reduction of esters to aldehydes is carried out with hydrides such as NaH2Al(0CH2CH20CH2)2, NaALH, or... 

LiAlH —(C2H )2NH. The use of BH or LiAlH —BE 0(C2H )2 as a reducing reagent converts esters to ethers. Thus, reduction of esters can be manipulated by the judicious selection of metal-containing reducing reagents. 

Reduction of esters to alcohols by means of sodium in alcohol... 

McFADYEN - STEVENS Ester Reduction Reduction of esters to aldehyde via hydrazides. 

Decamethylene glycol has been prepared by the reduction of dimethyl sebacate and diethyl sebacate with sodium and ethyl alcohol by the reduction of sebacamide with sodium and amyl alcohol and by the reduction of dimethyl sebacate with sodium and liquid ammonia in absolute alcohol. The reduction of esters with sodium and alcohol has also been applied to the preparation of many other glycols. ... 

The direct reduction of esters with diisobuty laluminum hydride in the presence of the Horner-Emmons reagent prepared from ethyl diethylphosphon-ofluoroacetate avoids the necessity to work with sensitive aldehydes in the olefi-nation procedure [72, 75] (equation 62) (Table 23). 

Aldehydes and ketones are among the most important of ail compounds, both in biochemistry and in the chemical industry. AUdehydes are normally prepared in the laboratory by oxidation of primary alcohols or by partial reduction of esters. Ketones are similarly prepared by oxidation of secondary alcohols or by addition of diorganocopper reagents to acid chlorides. 

Finally, the necessity arose for the synthesis of pentulose 21, labeled with, 3C on the central carbons, C-2 and C-3, for an independent biosynthetic study, which is reported in Section III.5.27 The doubly labeled ester 34 (Scheme 14) is readily available by a Wittig- Homer condensation of benzyloxyacetaldehyde with commercially available triethylphosphono-(l,2-l3C2)acetate. Chirality was introduced by the reduction of ester 34 to the allylic alcohol, which produced the chiral epoxide 35 by the Sharpless epoxidation procedure. This was converted into the tetrose 36, and thence, into the protected pentulose 37 by the usual sequence of Grignard reaction and oxidation. 

Reductions of Esters with Metals in the Presence of Trimethylchlorosilane 281... 

The products are liberated by hydrolysis of the aluminum alkoxide at the end of the reaction. Lithium aluminum hydride reduction of esters to alcohols involves an elimination step in addition to hydride transfers. 

The most widely used reagent for partial reduction of esters and lactones at the present time is diisobutylaluminum hydride (DiBAlH).83 By use of a controlled amount of the reagent at low temperature, partial reduction can be reliably achieved. The selectivity results from the relative stability of the hemiacetal intermediate that is formed. The aldehyde is not liberated until the hydrolytic workup and is therefore not... 

The drug candidate 1 was prepared from chiral cyclopentanol 10 as shown in Scheme 7.3. Reaction of 10 with racemic imidate 17, prepared from the corresponding racemic benzylic alcohol, in the presence of catalytic TfOH furnished a 1 1 mixture of diastereomers 18 and 19 which were only separated from one another by careful and tedious chromatography. Reduction of ester 18 with LiBH4 and subsequent Swern oxidation gave aldehyde 20 in 68% yield. Reductive animation of 20 with (R)-ethyl nipecotate L-tartrate salt 21 and NaBH(OAc)3 and subsequent saponification of the ester moiety yielded drug candidate 1. 

The DIBAL reduction of esters to aldehydes in the presence of phosphonate anions appears to solve problems of overreduction to alcohol and provides a good general method of 2-carbon homologation... 

Lauryl alcohol has been prepared by the reduction of the aldehyde with zinc dust and acetic acid 1 by the reduction of esters of lauric acid with sodium and absolute alcohol 2 or with sodium, liquid ammonia, and absolute alcohol 3 by the reduction of lauramide with sodium and amyl alcohol.4 The method in the above procedure is essentially that described by Levene and Allen.5... 

The combination of (EtO)3SiH/CsF (or KF) provides a convenient reagent for the reduction of esters to alcohols.76,80,83 The yields are in the 70% range. Potassium tetraethoxyhydridosilicate also reduces esters in moderate yields.288 The combination of PM HS/CpiTiCE/n-BuLi reduces esters in high yields even in the presence of an epoxide and a trisubstituted olefin (Eq. 140).289 The reagent combination can reduce a methyl ester in the presence of a tert-butyl ester (Eq. 141).290... 

Table 10. organosilane reduction of Esters and Lactones (continued)... 

---