Aluminum hydride, diisobutyl- DIBAL amides

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]. 

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.

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