Aluminum complexes alkoxy hydrides

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 ... 

A slightly more complex Scheme is required for preparation of an antihistaminic agent bearing a secondary amine, e. g., tofenacin (32). In the synthesis of tofenacin, alkylation of the benzhydrol (29) with ethyl bromoacetate affords the alkoxy ester (30) saponification followed by conversion to the methylamide gives (31), which is reduced with lithium aluminum hydride to complete the synthesis of 32. 10... 

Primary alkyl amines. a-Alkoxy azides are reduced to primary amines by lithium aluminum hydride in ether. A side reaction noted occasionally, reduction to an ether, can be suppressed by addition of TMEDA. Sodium bis(2-methoxy-ethoxy)aluminum hydride cannot replace lithium aluminum hydride in this reductive amination. The a-alkoxy azides are available by reaction of aldehydes with azidotrimethylsilane, by addition of hydrazoic acid to an enol ether, or by reaction of ketals with the l8-crown-6 complex of sodium azide. 

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