Esters aldehyde synthesis, diisobutylaluminum hydride

Meroquinene aldehyde and meroquinene alcohol, which were also employed in the synthesis of Cinchona alkaloids, were prepared as described below. Reduction of iV-benzoylmeroquinene methyl ester (31) with diisobutylaluminum hydride in toluene at — 78°C 16) and subsequent benzoylation of the crude amino aldehyde 53 gave the liquid... 

The nucleophilic attack on an acceptor-substituted allene can also take place at the acceptor itself, especially in the case of carbonyl groups of aldehydes, ketones or esters. Allenic esters are reduced to the corresponding primary alcohols by means of diisobutylaluminum hydride [18] and the synthesis of a vinylallene (allenene) by Peterson olefination of an allenyl ketone has also been reported [172]. The nucleophilic attack of allenylboranes 189 on butadienals 188 was investigated intensively by Wang and co-workers (Scheme 7.31) [184, 203, 248, 249]. The stereochemistry of the obtained secondary alcohol 190 depends on the substitution pattern. Fortunately, the synthesis of the desired Z-configured hepta-l,2,4-trien-6-ynes 191 is possible both by syn-elimination with the help of potassium hydride and by anti-elimination induced by sulfuric acid. Analogous allylboranes instead of the allenes 189 can be reacted also with the aldehydes 188 [250]. 

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... 

The other stereoselective synthesis/281 shown in Scheme 8, foresees conversion of Boc-L-Asp-OtBu 20 into the related (3-aldehyde 22 via the Weinreb amide 21 and its reduction with diisobutylaluminum hydride (DIBAL-H). Wittig condensation of 22 with the ylide derived from (3-carboxypropyl)triphenylphosphonium bromide using lithium hexamethyldisilaza-nide at —78 to 0°C, produces the unsaturated compound 23 which is catalytically hydrogenated to the protected L-a-aminosuberic acid derivative 24. Conversion of the co-carboxy group into the 9-fluorenylmethyl ester, followed by TFA treatment and reprotection of the M -amino group affords Boc-L-Asu(OFm)-OH (25). 

For example, the partial reduction of an ester by diisobutylaluminum hydride (DIBAH) is an important laboratory-scale method of aldehyde synthesis. The reaction is normally carried out at -78°C (dry-ice temperature) in toluene solution. 

A third method of aldehyde synthesis is one that we ll mention here just briefly and then return to in Section 21.6. Certain carboxylic acid derivatives can be partially reduced to yield aldehydes. The partial reduction of an ester by diisobutylaluminum hydride (DIBAH) for instance, is an important laboratory-scale method of aldehyde synthesis, and mechanistically related processes also occur in biological pathways. The reaction is normally carried out at -78 °C (dry-ice temperature) in toluene solution. 

The synthesis of naturally occurring A-acetylneuraminic acid (912) utilizes the chirality of D-lactate (898) to set the stereochemistry of hetero Diels-Alder adduct 910 [247] (Scheme 121). The dienophile, ( S)-seleno aldehyde 908, is prepared by inversion of mesylate 906 followed by controlled reduction of the ester with diisobutylaluminum hydride at low tern-... 

The synthesis of trans-3-acyl- 3-lactam methyl esters 107 has been reported by Almqvist and coworkers [81, 82] by the Staudinger reaction of ketenes, generated from the Meldrum s acids 105, with methyl (i )-thiazoline-4-carboxylate 106 in benzene in the presence of hydrogen chloride (Scheme 3.36). An exceptionally low yield of 38% was obtained in the reaction of acetylketene. These esters could then be selectively reduced to the corresponding aldehydes 108 in moderate yields using diisobutylaluminum hydride (DIBAL-H). The Meldrum acids are well-known precursors of ketenes [83, 84]. They undergo a pericyclic reaction under thermal influence to generate ketenes with the release of carbon monoxide and acetone. 

As shown in Scheme 5, the enantiocontrolled synthesis of the (S)-14 was started from 4-(methoxyethyl)phenol 15 which was converted to the 2,2-difluoroester 16 in 73% yield by treatment with chlorodifluoroacetic acid and sodium in refluxing dioxane (50) followed by esterification with iodoethane. The ester 16 was reduced with diisobutylaluminum hydride to afford the 2,2-difluoro aldehyde 17 in 80% yield. The aldehyde 17 was allowed to react with nitromethane at -40 C in the presence of 8 mol% of the Sm-Li-(/ )-BINOL complex to provide the difluoro nitroaldol (S)-18 with 75% ee in 52% yield. After a single recrystallization, the enantiomerically pure nitroaldol (S)-18 (>99% ee) was recovered from the mother liquor in 65% yield. Reductive alkylation of the homochiral nitroaldol (i -18 was acconiplished by PtOa-catalyzed hydrogenation in the presence of acetone in methanol to give (S)-14 in 89% yield (51), In the same manner, the nitroaldol (i )-18 obtained using Sm-Li-(S)-BINOL was converted to the enantiomerically pure (/ )-14. 

Diisobutylaluminum hydride (DIBAL) is known to be less reactive than LiAUL and can transfer only one hydride ion per molecule. For this reason DIBAL is commonly used for partial reduction of esters and nitriles. Addition of DIBAL to a nitrile results in the formation of an imine-aluminum complex that is decomposed, during workup, to the aldehyde (Scheme 14). Cyanohydrins have to be protected during the synthesis of a-hydroxy aldehydes because dimerization and isomerization can take place. Even in the protected form special care has to be taken during synthesis (low temperatures) and workup [124,136]. 

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