Tri-ferf-butoxyaluminum hydride

Several synthetic methods for the reduction of a-amino esters have also been reported. The reduction of methyl or ethyl esters by diisobutylaluminum hydride (DIBAL-H) at low temperature (—78 °C) has been described as useful for the preparation of a-amino aldehydes. 1118 20 Again, this method suffers from overreduction. Reductive methods involving mild reductive agents have been described. The reduction of phenyl esters 6 21 (readily prepared from the corresponding amino acid 5) with lithium tri-ferf-butoxyaluminum hydride is efficient for the preparation of various Boc-a-amino aldehydes including Na-Boc-7V J-nitroargininal and A7a-Boc-W"-Z-argininal (Scheme 5). 

Reduction to Aldehydes Reduction of carboxylic acids to aldehydes is difficult because aldehydes are more reactive than carboxylic acids toward most reducing agents. Almost any reagent that reduces acids to aldehydes also reduces aldehydes to primary alcohols. In Section 18-10, we saw that lithium tri-ferf-butoxyaluminum hydride, LiAlH(0-f-Bu)3 is a weaker reducing agent than lithium aluminum hydride. It reduces acid chlorides to aldehydes because acid chlorides are strongly activated toward nucleophilic addition of a hydride ion. Under these conditions, the aldehyde reduces more slowly and can be isolated. Therefore, reduction of an acid to an aldehyde is a two-step process Convert the acid to the acid chloride, then reduce using lithium tri-ferf-butoxyaluminum hydride. 

Acid chlorides are more reactive than other acid derivatives, and they are reduced to aldehydes by mild reducing agents such as lithium tri-ferf-butoxyaluminum hydride. Diisobutylaluminum hydride (DIBAL-H) reduces esters to aldehydes at low temperatures, and it also reduces nitriles to aldehydes. These reductions were covered in Sections 18-9,18-10, and 20-13. 

B-alkyl-9-BBN derivatives (p. 1077). Since only the 9-alkyl group migrates, this method permits the conversion in high yield of an alkene to a primary alcohol or aldehyde containing one more carbon." When B-alkyl-9-BBN derivatives are treated with CO and lithium tri-ferf-butoxyaluminum hydride," other functional groups (e.g., CN and ester) can be present in the alkyl group without being reduced." Boranes can be directly converted to carboxylic acids by reaction with the dianion of phenoxyacetic acid." " ... 

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

Cleavage of the C-Cl bond in a cyclopropanecarbonyl chloride occurs to give the corresponding cyclopropanecarbaldehyde the reagent used was lithium tri-ferf-butoxyaluminum hydride in an ethereal solvent.The yields were rather low. 

Replacing some of the hydrogens of LiAlH4 with OR groups decreases the reactivity of the metal hydride. For example, lithium tri-ferf-butoxyaluminum hydride reduces an acyl chloride to an aldehyde, whereas L1A1H4 reduces the acyl chloride all the way to an alcohol. 

A soln. of 3)5-(2 -tetrahydropyranyloxy)androst-5-ene-7,17-dione in tetrahydro-furan added at 0° to a soln. of Li tri-ferf-butoxyaluminum hydride in the same solvent, kept 9 min. at 0°, then poured into 5%-acetic acid 3y -(2 -tetrahydro-pyranyloxy)-17y -hydroxyandrost-5-en-7-one. Y 88%. F. e. s. J. Joska, J. Fajkos, and F. Sorm, Coll. 26, 1646 (1961). 

Reduction. A variety of metal hydride reducing agents can be employed to reduce jr-allylpalladium dimers. These include sodium borohydride, sodium cyanoborohydride, lithium triethylborohydride, lithium aluminum hydride, lithium tri-ferf-butoxyaluminum hydride, polymethylhydrosiloxane, and RsSiH (eq Formic acids and formate salts also reduce... 

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