Aldehydes ester conversions, diisobutylaluminum 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). 

The other stereoselective synthesis/281 shown in Scheme 8, foresees conversion of Boc-L-Asp-OtBu 20 into the related (3-aldehyde 22 via the Weinreb amide 21 and its reduction with diisobutylaluminum hydride (DIBAL-H). Wittig condensation of 22 with the ylide derived from (3-carboxypropyl)triphenylphosphonium bromide using lithium hexamethyldisilaza-nide at —78 to 0°C, produces the unsaturated compound 23 which is catalytically hydrogenated to the protected L-a-aminosuberic acid derivative 24. Conversion of the co-carboxy group into the 9-fluorenylmethyl ester, followed by TFA treatment and reprotection of the M -amino group affords Boc-L-Asu(OFm)-OH (25). 

The mechanism of diisobutylaluminum hydride reduction involves formation of a six-membered transition state with aluminum complexed to the carbonyl of the ester group, which is required for the delivery of the hydride from the electrophilic aluminum hydride to the carbonyl group. The alkoxy moiety is then displaced during workup resulting in the desired peptide aldehyde. This mechanism accounts for the fact that the reduction stops after the conversion of the ester into the aldehyde. 23 ... 

Partial reduction of the two ester groups in 4 with diisobutylaluminum hydride in toluene-hexane at —78 °C provides in situ a dialuminate which, as an aldehyde equivalent, reacts under Wittig—Homer conditions to provide good yields of the diolefin 24. Subsequent conversion of 24 to (4i ,5i )-l,8-(bisbenzyloxy)-2( ),6(E)-octadien-4,5-diol (25) provides the essential framework for a palladium(II)-catalyzed [3,3]-sigmatropic rearrangement to 2S,1S) 2,7-(bisacetoxy)-l,8-(bisbenzyloxy)-3(j, 5( )-octadiene (26) (Scheme 6). The orginal chirality is completely translated into the dissymmetric 3,5-octadiene framework, which has C2 chirality [18]. 

Other functionality can be incorporated into the ylid prior to reaction with an aldehyde or ketone. Aldehyde 1.195, for example was converted 1.196 by reaction with a fluorine-bearing phosphonate ylid. 5 The ester group was reduced to an aldehyde moiety (see 1.197) with diisobutylaluminum hydride. This allowed final conversion to 5-(N-Boc amino)-4-fluoro-6-phenylhex-3E-enoic acid (1.198), in four steps (3% overall yield the first and second steps gave a combined yield of 14% and step five proceeded in 28% yield). 

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