Diisobutyl aluminum hydride DIBAL

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.

Retinoyl imidazolide (616) was converted to retinaldehyde (2), using lithium aluminum hydride (Staab and Mannschreck, 1962). Retinonitrile (156) reacted with diisobutyl aluminum hydride (DIBAL) to give (2) (Kaegi etal., 1982). The nitrile (156) was obtained via the cyanoretinoic acid (155) by condensation of the C,8 ketone (136) or its Schiff base with cyanoacetic acid (Pommer, 1960 Smit, 1961). 

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... 

Retroretinaldehyde (282) was synthesized from a-ionone (279) in two reaction sequences employing the phosphonates (280) and (220), with the product of each step being reduced with diisobutyl aluminum hydride (DIBAL) (Hale et ai,... 

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). 

To synthesize 7-di -retinaldehydes, a mixture of the two nitriles (104) and (105) was reacted with diisobutyl aluminum hydride (DIBAL) to give the C15 aldehydes (349) and (350), which were condensed with acetone to give a mixture of the ketones (351) and (352), both of which possessed a trans configuration at the newly formed double bond. The mixture of these Cjg ketones reacted... 

To synthesize the retinoidal benzaldehyde derivative (658), the ketone (656) was coupled to the benzylphosphonate (657) in the anionic form, and the product was reduced with diisobutyl aluminum hydride (DIBAL) (Matsumoto et aLy 1980). 

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... 

Acylthiazolidine-2-thiones (593), easily prepared from carboxylic acids and thiazolidine-2-thione, can be reduced to the corresponding aldehydes with diisobutyl-aluminum hydride in toluene at -78 to -40 °C in 70-90% yield or with lithium tri-f-butoxyaluminum hydride in THF at -20 to 0 °C in 80-90% yield (Scheme 130) (79BCJ555). The formation of the aluminum-containing six-membered chelate (594) in this reaction process is probable and is supported by the fact that no decrease in yield is observed on changing the mole ratio of DIBAL from 1.2 to 2.1 equivalents. 

Reagents (a) Diisobutyl aluminum hydride (b) 4-lithiomethyl-6-methoxyquinoline (c) NBS, hv and DIBAL (d) DIBAL, Tol. (e) BF3.Et20, AcOH (f) heat (g) O2, DMSO, t-BuOH, f-BuOK. 

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. 

SCHEME 3 Synthesis of ( )-sesquicillin [( )-2]. Ms, methanesulfonyl DIBAL, diisobutyl-aluminum hydride TMS, trimethylsilyl LDA, lithium diisopropylamide, DMAP, 4-dimethylaminopyridine DBU, l,8-diazabicyclo[5.4.0]undec-7-ene. 

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. ... 

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