Lithium aluminum hydride reactions with esters

In general, on reaction with lithium aluminum hydride, secondary sulfonic esters are desulfonylated, with formation of the corresponding secondary alcohol. An exception is provided in an observation by Reist and coworkers, who treated 6-0-benzoyl-l,2-0-isopropyli-dene-5-O-p-tolylsulfonyl-a-D-glucofuranose, with lithium aluminum hydride in ether and obtained a product thought to be 6-deoxy-l,2-0-isopropylidene-y3-L-idofuranose, derived from an intermediate 5,6-anhydro-L-ido derivative later, Ryan and coworkers showed, from its nuclear magnetic resonance spectrum, that the product was 5-deoxy-l,2-0-isopropylidene-a-D- t/Zo-hexofuranose. The problem has been re-examined by Overend and coworkers the repetition experiment under the conditions of Reist and coworkers afforded 5-deoxy-... 

Sodium metal in conjunction with a protic solvent such as an alcohol is sometimes used as a less expensive substitute for lithium aluminum hydride for reducing esters to alcohols in an industrial setting. This is the Bouveault-Blanc reaction. A modem version of this old reaction employs sodium-in-silica-gel (Na-SG), a safe fi ee-flowing powder, instead of the bulk metal (B. S. Bodnar, P. F. Vogt, J. Org. Chem. 2009, 74, 2598-2600) ... 

Consider the reaction of lithium aluminum hydride with an ester (Figure 15.34). The hydride will attack the carbonyl to give a tetrahedral intermediate, just as with aldehydes and ketones. However, this tetrahedral intermediate does not wait around to be protonated but loses ethoxide to give an aldehyde. We already know how lithium aluminum hydride reacts with aldehydes, and our final product, after work-up, is a primary alcohol. 

The reaction of esters with Gngnard reagents and with lithium aluminum hydride both useful m the synthesis of alcohols were described earlier They are reviewed m Table 20 4 on page 848... 

An aiyl methane- or toluenesulfonate ester is stable to reduction with lithium aluminum hydride, to the acidic conditions used for nitration of an aromatic ring (HNO3/HOAC), and to the high temperatures (200-250°) of an Ullman reaction. Aiyl sulfonate esters, formed by reaction of a phenol with a sulfonyl chloride in pyridine or aqueous sodium hydroxide, are cleaved by warming in aqueous sodium hydroxide. ... 

The reaction of esters with Gr-ignard reagents and with lithium aluminum hydride, both useful in the synthesis of alcohols, were described earlier. They are reviewed in Table... 

LY311727 is an indole acetic acid based selective inhibitor of human non-pancreatic secretory phospholipase A2 (hnpsPLA2) under development by Lilly as a potential treatment for sepsis. The synthesis of LY311727 involved a Nenitzescu indolization reaction as a key step. The Nenitzescu condensation of quinone 4 with the p-aminoacrylate 39 was carried out in CH3NO2 to provide the desired 5-hydroxylindole 40 in 83% yield. Protection of the 5-hydroxyl moiety in indole 40 was accomplished in H2O under phase transfer conditions in 80% yield. Lithium aluminum hydride mediated reduction of the ester functional group in 41 provided the alcohol 42 in 78% yield. 

A substituted benzoic acid serves as precursor for the nontricyclic antidepressant bipena-mol (175). Selective. saponification of ester 171 afford.s the half-acid 172. Reaction of the acid chloride derived from this intermediate (173) with ammonia gives the amide 174. Reduction of the last by means of lithium aluminum hydride gives bipenamol (175) [44]. 

The preparation of Pans-1,2-cyclohexanediol by oxidation of cyclohexene with peroxyformic acid and subsequent hydrolysis of the diol monoformate has been described, and other methods for the preparation of both cis- and trans-l,2-cyclohexanediols were cited. Subsequently the trans diol has been prepared by oxidation of cyclohexene with various peroxy acids, with hydrogen peroxide and selenium dioxide, and with iodine and silver acetate by the Prevost reaction. Alternative methods for preparing the trans isomer are hydroboration of various enol derivatives of cyclohexanone and reduction of Pans-2-cyclohexen-l-ol epoxide with lithium aluminum hydride. cis-1,2-Cyclohexanediol has been prepared by cis hydroxylation of cyclohexene with various reagents or catalysts derived from osmium tetroxide, by solvolysis of Pans-2-halocyclohexanol esters in a manner similar to the Woodward-Prevost reaction, by reduction of cis-2-cyclohexen-l-ol epoxide with lithium aluminum hydride, and by oxymercuration of 2-cyclohexen-l-ol with mercury(II) trifluoro-acetate in the presence of ehloral and subsequent reduction. ... 

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

Conversion of ketone 80 to the enol silane followed by addition of lithium aluminum hydride to the reaction mixture directly provides the allylic alcohol 81 [70]. Treatment of crude allylic alcohol 81 with tert-butyldimethylsilyl chloride followed by N-b ro m o s u cc i n i m i de furnishes the a-bromoketone 82 in 84 % yield over the two-step sequence from a.p-unsaturated ester 80. Finally, a one-pot Komblum oxidation [71] of a-bromoketone 82 is achieved by way of the nitrate ester to deliver the glyoxal 71. It is worth noting that the sequence to glyoxal 71 requires only a single chromatographic purification at the second to last step (Scheme 5.10). 

The importance of reactions with complex, metal hydrides in carbohydrate chemistry is well documented by a vast number of publications that deal mainly with reduction of carbonyl groups, N- and O-acyl functions, lactones, azides, and epoxides, as well as with reactions of sulfonic esters. With rare exceptions, lithium aluminum hydride and lithium, sodium, or potassium borohydride are the... 

Countless reductions of esters to alcohols have been accomplished using lithium aluminum hydride. One half of a mol of this hydride is needed for reduction of 1 mol of the ester. Ester or its solution in ether is added to a solution of lithium aluminum hydride in ether. The heat of reaction brings the mixture to boiling. The reaction mixture is decomposed by ice-water and acidified with mineral acid to dissolve lithium and aluminum salts. Less frequently sodium hydroxide is used for this purpose. Yields of alcohols are frequently quantitative [83,1059]. Lactones afford glycols (diols) [575]. 

Much more conveniently, even a,)S-unsaturated esters can he transformed into a,)S-unsaturated alcohols by very careful treatment with lithium aluminum hydride [1073], sodium bis(2-methoxyethoxy)aluminum hydride [544] or diiso-butylalane [1151] (Procedure 18, p. 208). An excess of the reducing agent must be avoided. Therefore the inverse technique (addition of the hydride to the ester) is used and the reaction is usually carried out at low temperature. In hydrocarbons as solvents the reduction does not proceed further even at elevated temperatures. Methyl cinnamate was converted to cinnamyl alcohol in 73% yield when an equimolar amount of the ester was added to a suspension of lithium aluminum hydride in benzene and the mixture was heated at 59-60° for 14.5 hours [1073]. Ethyl cinnamate gave 75.5% yield of cinnamyl alcohol on inverse treatment with 1.1 mol of sodium bis(2-methoxy-ethoxy)aluminum hydride at 15-20° for 45 minutes [544]. 

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