Diisopropyl aluminum hydride

Further regio- and stereospecific reductive addition of the acetylene with diisopropyl aluminum hydride (DIBAL) in CH2C12, followed by D20, gave (+)-(lS,trans)-E-2-(ethenyl-2-d,)-methylcyclopropane (equation 158). 

An interesting deoxygenation of ketones takes place on treatment with low valence state titanium. Reagents prepared by treatment of titanium trichloride in tetrahydrofuran with lithium aluminum hydride [205], with potassium [206], with magnesium [207], or in dimethoxyethane with lithium [206] or zinc-copper couple [206,209] convert ketones to alkenes formed by coupling of the ketone carbon skeleton at the carbonyl carbon. Diisopropyl ketone thus gave tetraisopropylethylene (yield 37%) [206], and cyclic and aromatic ketones afforded much better yields of symmetrical or mixed coupled products [206,207,209]. The formation of the alkene may be preceded by pinacol coupling. In some cases a pinacol was actually isolated and reduced by low valence state titanium to the alkene [206] (p. 118). 

Similarly, lipase-catalyzed kinetic resolution has also been applied to intermediate nitrile alcohol 46 (Scheme 14.14). Best results were obtained by using immobilized Pseudomonas cepacia (PS-D) in diisopropyl ether, leading to excellent yield and enantiomeric excess of the desired (5)-alcohol 46a, along with (/J)-nitrile ester 47. Reduction of 46a with borane-dimethylsulhde complex, followed by conversion to the corresponding carbamate and subsequent lithium aluminum hydride reduction gave rise to the desired (S)-aminoalcohol intermediate 36, a known precursor of duloxetine (3). 

Hydroxymethyl-1,4-benzodioxin (137) obtained in 80% yield by reduction of ethyl 1,4-benzo-dioxin-2-carboxylate (39) with lithium aluminum hydride in refluxing ether <91TL5525> reacted with zinc azide bis-pyridine complex under Mitsunobu conditions (triphenylphosphine, diisopropyl azodicarboxylate) to yield exclusively compound (138) in 75% yield. Otherwise, (137) was first reacted with zinc iodide under the same conditions until complete transformation of the starting material into the mixture of regioisomers (139) and (140) excess of dry piperidine was then added to the crude reaction medium to yield the alkenic analogue (141) of Piperoxan <89TL1637>. 

In the benzo-fused series, 2,3-dihydro-2,3-dimethylene-l,4-benzodioxin (160) was obtained by the route outlined in Scheme 6. The 3-methyl substituted acid (158), obtained by methylation of the dianion of 2-carboxy-l,4-benzodioxin, was esterified and then reduced with lithium aluminum hydride to afford the allylic alcohol (159). The treatment of (159) with mesyl chloride at — 70°C in the presence of triethylamine afforded the required diene (160) in 80% overall yield. The Diels-Alder cycloaddition of the diene (160) with range of dienophiles (dimethyl alkynedicarboxylate, acrylonitrile, diisopropyl azodicarboxylate, methyl vinyl ketone, 2-vinylpyridine, 1,4-benzoquinone) gave, in good yields, the corresponding tricyclic adducts <92TL2965>. 

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