DIBAL hydride

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

Polyfluoro-l -aUcenyl phosphates are reduced under mild conditions by diisohuty-laluminum hydride (DIBAL) to the aluimniun enolate, which is denvatized by addition to benzaldehyde [96] (equation 78)... 

With the co side chain at C-12 in place, we are now in a position to address the elaboration of the side chain appended to C-8 and the completion of the syntheses. Treatment of lactone 19 with di-isobutylaluminum hydride (Dibal-H) accomplishes partial reduction of the C-6 lactone carbonyl and provides lactol 4. Wittig condensation8 of 4 with nonstabilized phosphorous ylide 5 proceeds smoothly and stereoselectively to give intermediate 20, the bistetra-hydropyranyl ether of ( )-1, in a yield of -80% from 18. The convergent coupling of compounds 4 and 5 is attended by the completely selective formation of the desired cis C5-C6 olefin. 

The isomerization of an allylic amine to an enamine by means of a formal 1,3-hydrogen shift constitutes a relatively small structural change. However, this transformation could be extremely valuable if it could be rendered stereoselective. In important early studies, Otsuka and Tani showed that a chiral cobalt catalyst, prepared in situ from a Co(ii) salt, a chiral phosphine, and diisobutylaluminum hydride (Dibal-H), can bring about the conversion of certain pro-chiral olefins to chiral, isomeric olefins by double bond migra-... 

When a cold (-78 °C) solution of the lithium enolate derived from amide 6 is treated successively with a,/ -unsaturated ester 7 and homogeranyl iodide 8, intermediate 9 is produced in 87% yield (see Scheme 2). All of the carbon atoms that will constitute the complex pentacyclic framework of 1 are introduced in this one-pot operation. After some careful experimentation, a three-step reaction sequence was found to be necessary to accomplish the conversion of both the amide and methyl ester functions to aldehyde groups. Thus, a complete reduction of the methyl ester with diisobutylalu-minum hydride (Dibal-H) furnishes hydroxy amide 10 which is then hydrolyzed with potassium hydroxide in aqueous ethanol. After acidification of the saponification mixture, a 1 1 mixture of diastereomeric 5-lactones 11 is obtained in quantitative yield. Under the harsh conditions required to achieve the hydrolysis of the amide in 10, the stereogenic center bearing the benzyloxypropyl side chain epimerized. Nevertheless, this seemingly unfortunate circumstance is ultimately of no consequence because this carbon will eventually become part of the planar azadiene. 

Detty published the first example of the titled approach in his pioneering work on teluropyrans (88MI1). The hexafluorophosphate 76 was reduced with diisobutyl aluminium hydride (DIBAL-H) to a 93 7 mixture of isomeric teluropyrans 77 and 78 accompanied by traces (ca. 1%) of the dimeric product 80. The latter was also obtained after the electrochemical reduction of 76 via radicals 79 or by a modification of the reduction with DIBAL-H (Scheme 5). 

Hydroxy-4//-selenopyrans 113 have been reported to be air-sensitive intermediates in the transformations of 100c to salts 73a and 73 (R = Me) by successive action of lithium aluminium hydride or methyllithium and then tetrafluoroboric acid (90AG450). 4//-Selenopyranone 100c was reduced to 4//-selenopyran 101c with DIBAL-H (88MI1). 

The procedure is outlined in Scheme 8.33, starting from the generic allylic alcohol 125. SAE on 125 would provide epoxide 126, which could easily be transformed into the unsaturated epoxy ester 127 by oxidation/Horner-Emmonds olefmation (two-carbon extension). This operation makes the oxirane carbon adjacent to the double bond more susceptible to nucleophilic attack by a hydride, so reductive opening (DIBAL) of 127 provides, with concomitant ester reduction, diol 128. Pro-... 

Diisobutylaluminum hydride (DIBAL-H) can also be used for partial reduction of cyclic imides37. Although less convenient than sodium borohydride, an important synthetic aspect is the fact that in the reduction of asymmetrically substituted imides, diisobutylaluminum hydride and sodium borohydride may show opposite regioselectivity38,39. 

Enantiomerically pure /J-keto sulfoxides are prepared easily via condensation of a-lithiosulfinyl carbanions with esters. Reduction of the carbonyl group in such /J-keto sulfoxides leads to diastereomeric /J-hydroxysulfoxides. The major recent advance in this area has been the discovery that non-chelating hydride donors (e.g., diisobutylaluminium hydride, DIBAL) tend to form one /J-hydroxysulfoxide while chelating hydride donors [e.g., lithium aluminium hydride (LAH), or DIBAL in the presence of divalent zinc ions] tend to produce the diastereomeric /J-hydroxysulfoxide. The level of diastereoselectivity is often very high. For example, enantiomerically pure /J-ketosulfoxide 32 is reduced by LAH in diethyl ether to give mainly the (RR)-diastereomer whereas DIBAL produces exclusively the (.S R)-diastereomer (equation 30)53-69. A second example is shown in... 

The other way of reducing nitriles to aldehydes involves using a metal hydride reducing agent to add 1 mol of hydrogen and hydrolysis, in situ, of the resulting imine (which is undoubtedly coordinated to the metal). This has been carried out with LiAlH4, LiAlH(OEt)3, LiAlH(NR2)3, and DIBAL-H. The metal hydride method is useful for aliphatic and aromatic nitriles. 

Mehta et al. also studied the facial selectivities of 5,6-exo,eji o-disubstituted bicyclo[2.2.2]octan-2-ones 18 [75, 78]. These systems are related to the 2,3-exo,ex( -disubstituted 7-norbomanones 14, but differ in the direction of the carbonyl n face. Hydride reduction of 5,6-exo,ex( -disubstituted bicyclo[2.2.2] octan-2-ones (18) with NaBH and DIBAL-H and methylation with MeLi were smdied [75, 78],... 

Scheme 10. Synthesis of the ds-donor-acceptor-substituted TEE 86 [ 100]. DIBAL-H diisobutylaluminum hydride, PCC pyridinium chlorochromate, LDA lithium diisopropylamide...

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