Aluminum hydride, diisobutyl- DIBAL reduction

Reduction of sulfones to sulfides has been accomplished by lithium aluminum hydride [687], diisobutyl aluminum hydride [659] and sometimes by zinc dust in acetic acid [657]. Diisobutyl aliuninum hydride (Dibal-H) was found to be superior to both lithium alumimun hydride and zinc. At least 2.2 mol of the hydride were necessary for the reduction carried out in mineral oil at room... 

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-... 

The Stork-Dolfini synthesis of the amino ketone 458 requires some 11 steps clearly, this is an area for improvement. One method used has been that of methyl vinyl ketone annelation (237). This procedure had been used previously in a synthesis of mesembrine (238) involving 2- -rolines. Stevens hoped to extend this technique to endocyclic enamines to give compounds in the octahydroquinolone series. 3-Ethylpiperid-2-one (549) was prepared from the y-lactone 550 according to standard procedures (239). N-Benzylation followed by reduction with diisobutyl-aluminum hydride (DIBAL) gave enamine 473. Addition of the enamine to methyl vinyl ketone (551) gave an almost quantitative yield of a hydroquinoline 552, which could be readily debenzylated to the known amino ketone 458. As with the Stork method of synthesis, this route to the Aspidosperma nucleus is efficient for the parent compounds but appears to lack the potential for diversification required to synthesize the more complex alkaloids such as vindoline (101) or even tabersonine (28). 

Scheme 9.107. A cartoon representation of the reduction 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]2AIH) in methylbenzene [toluene (CaHsCHs)] solution at low temperatures.

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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