Lithium tri-tert-butoxyaluminum

Reduction of acid halides with lithium tri-tert-butoxyaluminum hydride is an effective method for synthesis of amino aldehydes. Nonfunctionalized amino aldehydes 22 are readily prepared from respective reduction of the N-terminal Fmoc, Boc, or Z acid chlorides or fluorides 21 (Scheme 8, Table 9). This method afforded these aldehydes in about 60% yield with small differences in optical rotation as compared to literature values 11,33 48 54 55 ... 

Acyl chlorides can be reduced by reacting them with lithium tri-tert-butoxyaluminum hydride at -78°C. 

Lithium tri-tert-butoxyaluminum hydride, LiAlH[OC(CH3)3]3, has three electronegative oxygen atoms bonded to aluminum, which make this reagent less nucleophilic than LiAlH4. 

The best way to prepare peptide aldehydes from the corresponding N -protected amino acids is by using a handle based on the Weinreb amide.f This commercial handle allows classical solid-phase elongation of peptides using protected Boc or Fmoc amino adds and, at the end of the synthesis, the peptide aldehyde is formed by reduction and concomitant cleavage from the resin with lithium aluminum hydride. Although the 4-hydro-xybenzoic acid handle also allows the preparation of peptide aldehydes by reduction of the resin-bound phenyl ester with lithium tri-tert-butoxyaluminum hydride, a noixture of the aldehyde and the alcohol is always formed. 

The aldehyde intermediate can be isolated if a less powerful reducing agent such as lithium tri-tert-butoxyaluminum hydride is used in place of LiAlH4. This reagent, which is obtained by reaction of LiAlH4 with 3 equivalents of lert-butyl alcohol, is particularly effective for carrying out the partial reduction of acid chlorides to aldehydes (Section 19.2). 

There are many synthetic examples where hydride reduction of complex molecules proceeds with high dia-stereoselectivity. Reduction of 326a to alcohol 327 with lithium tri-tert-butoxyaluminum hydride is taken from Donaldson s synthesis of the C3-C15 bis(oxane) segment of phorboxazole. Oi The conformational drawing (326b) reveals that path a is preferred in the more stable chair conformation with the two substituents in the equatorial position. This model predicts the major alcohol product, which was converted as the acetate. 

Reduction of the intermediate generated from a carboxylic acid and DMFCl provides aldehydes with lithium tri-tert-butoxyaluminum hydride, and alcohols with sodium borohydride, both in high yield and chemoselectivity. 

Lithium tri-t-butoxyaluminum hydride readily reduces aldehydes and ketones to the corresponding alcohols and reduces acid chlorides to aldehydes. Epoxides, esters, carboxylic acids, tert-amides, and nitriles are not, or only slowly, reduced. Thus, the reagent may be used for chemoselective reductions. ... 

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