Reduction Using DIBAL

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

Lautens and Chiu123 reported a reductive ring opening of oxabicyclo[/z.2.1]alkenes 93 using DIBAL in the presence of bis(cyclooctadiene)nickel to give the racemic cycloalkanols (Scheme 10). 

The ylide 140 <2000JOC8068> is stable to attempted reduction using sodium borohydride, diisobutylaluminium hydride (DIBAL-H), or lithium aluminium hydride <2000JOC6388>, but eliminates propene on heating to form the annulated parent 141. Oxidation of the latter with lead(iv) oxide and potassium carbonate forms a radical, 142, which is stable to chromatography and can be stored in air for several days. 

Substituted succinonitriles give 3-substituted pyrroles on reduction with DIBAL-H (84TL1659) via diimine intermediates which undergo cyclization and aromatization (Scheme 39). This reaction was used in the synthesis of unusual pyrroles (e.g. 119) which were used to prepare sterically shielded porphyrins (94AG(E)889). 

Chiral sulfoxides are useful both as intermediates and target molecules of synthetic elaboration. The /J-amino-y-hydroxysulfoxidc moiety is one type of chiral sulfoxide which is the intermediate target in the synthesis of (5 )-(+)-sparsomycin. In the key step in this synthesis, the sought after moiety was produced by asymmetric reduction of an oxazoline using DIBAL, in the presence of zinc chloride and at — 78 °C (equation 79)326. 

One of the most reactive 1,3-dicarbonyl compounds used in the domino-Knoevenagel-hetero-Diels-Alder reaction is N,N-dimethyl barbituric acid 2. It has been shown that the fairly stable products can easily been transformed into other compounds via a reduction of the urea moiety with DIBAL-H [20]. Thus, reaction of 30 with DIBAL-H at 78 °C led to 46, which can be hydrolyzed to give 47 (Scheme 5.9). In a similar way, 48 was transformed into 50 via 49 and 12 to 52 via 51. The obtained compounds containing a lactone and an amide moiety can again be further transformed using DIBAL-H followed by an elimination. In this way, dihydropyran 54 is obtained from 50 via 53 as one example. 

Compared to other direct reductions of carboxylic acids or carboxylic acid derivates such as using DIBAL-H or Rosenmund conditions, the Fukuyama Reduction is a mild alternative, offering outstanding functional group tolerance. 

Reduction with NaBH4 or DIBAL-H furnished a product mixture in which the equatorial allylic alcohol predominated. However, reduction using K-Selectride produced the axial alcohol as the major product (88% yield, 9.8 1 mixture of diastereomers). 

Chiral addition of allyl metals to imines is one of the useful approaches toward the synthesis of homoallylic amines. These amines can be readily converted to a variety of biologically important molecules such as a-, / -, and y-amino acids. Itsuno and co-workers utilized the allylborane 174 derived from diisopropyl tartrate and cr-pinene for the enantioselective allylboration of imines. The corresponding iV-aluminoimines 173 are readily available from the nitriles via partial reduction using diisobutylaluminium hydride (DIBAL-H) <1999JOM103>. Recently, iV-benzyl-imines 176 have also been utilized for the asymmetric allylboration with allylpinacol boronate 177 in the presence of chiral phosphines as the chiral auxiliaries to obtain homoallylic A -benzylamines 178 in high yield and selectivity (Scheme 29) <2006JA7687>. 

Barrett used the reaction at the start of his synthesis of an antibiotic.12 The HWE reaction with the enal 47 gives the diene ester 48 and by reduction with DIBAL, the dienol 49. 

Reduction of the carbonyl group using DIBAL at low temperatures afforded the desired alcohol with complete diastereoselectivity. Deprotection yielded the protected a-hydroxyketone in good yield and with > 98% ee (Scheme 24). 

Selective reduction of the methyl ester to the corresponding aldehyde using DIBAL at low temperature and subsequent reductive amination with iodopiperonyl-ammonium chloride affords the tricarbonyliron-cyclohexadiene complex with the secondary alkylamine in the side chain. Iron(O)-mediated oxidative cydization... 

One step in a lengthy synthesis of ciguatoxin CTX3C involved selective reduction of an ester to an aldehyde using DIBAL-H. 

No doubt joining the alkyne to the alkene could also have been done by a coupling reaction in the coordination sphere of a metal but an alternative is to imagine the alkene as coming from the dehydration of an alcohol 251. This allows disconnection to the known lactone 250. The synthesis of the alkyne uses DIBAL for partial reduction and the differential protection of the two OH groups by more or less hindered silyl groups. 

The most straightforward application of the cyclocondensation reactions of aldehydes with activated dienes is in the synthesis of simple monosaccharides.- Condensation of diene (100) with benzyloxyacet-aldehyde (9a) using Bp3-Et02 as a catalyst, followed by treatment with TFA, gives the dihydropyrone (102). Reduction of (102) using DIBAL-H followed by hydroxylation of the glycal gives, after deprotection, talose (103 Scheme 30). 

However, it became obvious that the oxidation route would be the preferred one as it uses safer reactants than the reduction route (DIBAL-H). In addition, the oxidation reaction performed at room temperature represented a major advantage compared to the reduction route that has to be performed at low temperature to avoid overreduction by-products. 

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