Aluminum hydride, diisobutyl- DIBAL esters

The reason why the carbonyl group in -santonin remained intact may be that, after the reduction of the less hindered double bond, the ketone was enolized by lithium amide and was thus protected from further reduction. Indeed, treatment of ethyl l-methyl-2-cyclopentanone-l-carboxylate with lithium diisopropylamide in tetrahydrofuran at — 78° enolized the ketone and prevented its reduction with lithium aluminum hydride and with diisobutyl-alane (DIBAL ). Reduction by these two reagents in tetrahydrofuran at — 78° to —40° or —78° to —20°, respectively, afforded keto alcohols from several keto esters in 46-95% yields. Ketones whose enols are unstable failed to give keto alcohols [1092]. 

Reduction. At -78°, selective reduction of l-alkylindole-2,3-dicarboxylic esters at the C-2 substituent (to a CHO group) by Dibal-H is observed. Generally, the ester to aldehyde conversion can be performed at 0° with alkali metal diisobutyl(t-butoxy)aluminum hydride, which is formed by adding t-BuOM (M = Na, Li) to Dibal-H in THF. ... 

Numerous procedures have been reported for the synthesis of iV-protected-a-amino aldehydes [78]. The A-protected a-amino aldehydes can be prepared either by oxidation of the corresponding A-protected j8-amino alcohols with oxidants such as pyridinium dichromate [79,80] or SOs-pyridine-di-methyl sulfoxide (DMSO) [81] or under Swem conditions [DMSO-oxalyl chloride-A,A-diisopropylethylamine (DIEA)] [81-83], by reduction of esters with diisobutyl aluminum hydride (DIBAL) [84], by reduction of A,A-disubstituted amides [85-87], by reduction of urethane-protected A-carboxy-... 

Scheme 9.108. A cartoon representation of the reduction of an ester (L = OR ) and an N,N-disubstituted amide (L = NR2) of 2-phenylethanoic acid (2-phenylacetic acid, a-phenylacetic acid, C6H5CH2CO2H) to the corresponding aldehyde 2-phenylethanal (2-phenylacetaldehyde, a-phenylacetaldehyde, C6H5CH2CHO) with diisobutyl aluminum hydride (DIBAL-H, [(CH3)2CHCH2]2A1H) in methylbenzene [toluene (CeHsCHs)] solution at low temperatures.

The resulting mixture of E and Z isomers of the C15 ester (262) was reduced with diisobutyl aluminum hydride (DIBAL), purified by chromatography, and oxidized to give the C15 aldehyde (263), which was linked to the C5 phosphonate... 

The acid (307) was esterified in a basic medium to give the ester (308), which was reduced with diisobutyl aluminum hydride (DIBAL) to give virtually colorless, crystalline (3/ )-3-hydroxyretinol (309). The latter compound decomposed slowly. Conventional oxidation of the allylic hydroxyl group with man-ganese(IV) oxide gave (3/ )-3-hydroxyretinaldehyde (310). 

The aldehyde intermediate can be isolated if 1 equivalent of diisobutyl-aluminum hydride (DIBAH, or DIBAL-H) is used as the reducing agent instead of UAIH4. The reaction has to be carried out at -78 °C to avoid further reduction to the alcohol. Such partial reductions of carboxylic acid derivatives to aldehydes also occur in numerous biological pathways, although the substrate is either a thioester or acyl phosphate rather than an ester. 

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