Reduction of methyl esters

Chemoselective reduction of methyl ester 7 to aldehyde 2 is possible with DIB AH. The metallatcd hemiacetal that results from addition of DIBAII to the carbonyl group of ail ester usually decomposes rapidly in polar solvents like THF to an intermediate aldehyde This then competes with the ester and, as a result of its higher clcctrophilicity. js reduced by DIBAH to an alcohol. However, ester 7 bears a methoxymethyl residue in its a-position, which stabilizes the metallated hemiacetal by chelate formation. Chelate complex 22 is protolytically cleaved by way of the hemiacetal only in the course of aqueous workup, so in this case the DIBAH reaction produces only aldehyde 2, not the alcohol (see also Chapter 3), DIBAH, THF, -78 C 100. ... 

Sodium borohydride in combination with acetanilide or benzanilide also is effective for selective reduction of methyl esters other functional groups (amide, nitrile, isopropyl esters) are not reduced. ... 

Lactaldehyde derivative 808 can be prepared in high yield by direct reduction of methyl ester 807 with diisobutylaluminum hydride at low temperature [129]. 

Lithium aluminum hydride reduction of methyl esters Additive reduction... 

Figure 4.53 Reductions of methyl esters with sodium borohydride...

Reduction with sodium in alcohol was unsuccessful (54). The introduction of lithium aluminium hydride has provided an elegant method for the reduction of thiazole esters to hydroxythiazoles for example, ethyl 2-methyl-4-thiazolecarboxylate (11 with lithium aluminium hydride in diethyl ether gives 2-methyl-4-(hydroxymethyl)thiazole (12) in 66 to 69% yield (Scheme 7) (53),... 

Scheme 65 summarizes Mori s synthesis of 44 [97]. Reduction of keto ester A with baker s yeast gave hydroxy ester B of about 98% ee. Methylation of the dianion derived from B diastereoselectively gave C, which was converted to 44. This process enabled the preparation of about 10 g of (lS,5R)-44. 

Treatment of the alcohol 211 with f-butyklimethylsilyl triflate and 2,6-lutidine affords disiloxyester 212 with high yield. Reduction of the ester function of 212 with DIBAL followed by Swern oxidation gives the corresponding aldehyde 213, and subsequent alkylation with MeMgBr and Swern oxidation produce methyl ketone 214 (Scheme 7-70). 

Reaction of D-glucono-1,4-lactone with 2,2-dimethoxypropane-tin(II) chloride yields the 5,6-0-isopropylidene derivative 13, which on periodate oxidation afforded 2,3-0-isopropylidene-D-glyceraldehyde (21). However, the acid-catalyzed isopropylidenation of D-glucono-1,5-lactone with 2,2-dimethoxypropane afforded methyl 3,4 5,6-di-0-isopropylidene-D-gluco-nate (14) as the main product (22). Reduction of the ester function gave... 

Carboxvalkvlation of Propylene Oxide. These reagents were also used in a similar carboxyalkylation scheme to prepare methyl 3-hydroxybutyrate by reaction with propylene oxide (Equation 3). This might represent a way to prepare substitute 1,3 diols(48) following reduction of the ester or reactive monomers by pyrolys is/dehydration. 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

Reductions of keto esters to esters are not very frequent. Both Clemmensen and Wolff-Kizhner reductions can hardly be used. The best way is desulfurization of thioketals with Raney nickel (p. 130). Thus ethyl acetoacetate was reduced to ethyl butyrate in 70% yield, methyl benzoylformate (phenylglyoxy-late) to methyl phenylacetate in 79% yield, and other keto esters gave equally high yields (74-77%) [82J]. 

Alkyl alkanoates are reduced only at very negative potentials so that preparative scale experiments at mercury or lead cathodes are not successful. Phenyl alkanoates afford 30-36% yields of the alkan-l-ol under acid conditions [148]. Preparative scale reduction of methyl alkanoates is best achieved at a magnesium cathode in tetrahydrofuran containing tm-butanol as proton donor. The reaction is carried out in an undivided cell with a sacrificial magnesium anode and affords the alkan-l-ol in good yields [151]. In the absence of a proton donor and in the presence of chlorotrimethylsilane, acyloin derivatives 30 arc formed in a process related to the acyloin condensation of esters using sodium in xylene [152], Radical-anions formed initially can be trapped by intramolecular addition to an alkene function in substrates such as 31 to give aiicyclic products [151]. 

Acetaldehyde is obtained from the reaction of synthesis gas with methanol, methyl ketals or methyl esters. The reactions are carried out with an iodide-promoted Co catalyst at 180-200 °C and 2000-5000 psig. In comparing the various feedstocks, the best overall process to make acetaldehyde involves the reductive carbonylation of methyl esters. In this case, acetaldehyde selec-tivities are > 95% ut acceptable rates and conversion. 

Reductive Carbonylation of Methyl Esters. The best alternative, and in our opinion, the best reported synthesis gas based process to produce acetaldehyde, is the reductive carbonylation of methyl esters. Equation 15 (16). 

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