Lithium tri-f-butoxyaluminum hydride

The key intermediate 124 was prepared starting with tryptophyl bromide alkylation of 3-acetylpyridine, to give 128 in 95% yield (Fig. 37) [87]. Reduction of 128 with sodium dithionite under buffered (sodium bicarbonate) conditions lead to dihydropyridine 129, which could be cyclized to 130 upon treatment with methanolic HC1. Alternatively, 128 could be converted directly to 130 by sodium dithionite if the sodium bicarbonate was omitted. Oxidation with palladium on carbon produced pyridinium salt 131, which could then be reduced to 124 (as a mixture of isomers) upon reaction with sodium boro-hydride. Alternatively, direct reduction of 128 with sodium borohydride gave a mixture of compounds, from which cyclized derivative 132 could be isolated in 30% yield after column chromatography [88]. Reduction of 132 with lithium tri-f-butoxyaluminum hydride then gave 124 (once again as a mixture of isomers) in 90% yield. 

Acyl halides can be reduced to aldehydes1206 by treatment with lithium tri-f-butoxyaluminum hydride in diglyme at -78°C,1207 R may be alkyl or aryl and may contain many types of substituents, including N02, CN, and EtOOC groups. The reaction stops at the aldehyde stage because steric hindrance prevents further reduction under these conditions. Acyl halides can also be reduced to aldehydes by hydrogenolysis with palladium-on-barium sulfate... 

A cold (0°) solution of 15 g (0.039 mole) of cholest-4-en-3-one, mp 79-80°, in 200 ml of ether-benzene (8 1) is added dropwise to 0.05 mole of lithium tri-f-butoxyaluminum hydride in ether-diglyme at —40° to —50°. The mixture is allowed to stand overnight at 0° and then hydrolyzed by treatment with ice, 5 N sodium hydroxide and Rochelle salt. Evaporation of the washed and dried ether extracts and crystallization of the residue from ethyl acetate affords 13 g (87 % yield) of nearly pure cholest-4-en-3/ -ol, mp 126-129°. One recrystallization from the same solvent gives the pure product as large needles mp 131-132°, [a]D 46° reported mp 132° [a]D 44° (benzene). 

Acylthiazolidine-2-thiones (593), easily prepared from carboxylic acids and thiazolidine-2-thione, can be reduced to the corresponding aldehydes with diisobutyl-aluminum hydride in toluene at -78 to -40 °C in 70-90% yield or with lithium tri-f-butoxyaluminum hydride in THF at -20 to 0 °C in 80-90% yield (Scheme 130) (79BCJ555). The formation of the aluminum-containing six-membered chelate (594) in this reaction process is probable and is supported by the fact that no decrease in yield is observed on changing the mole ratio of DIBAL from 1.2 to 2.1 equivalents. 

Modified lithium aluminum hydride has been used successfully for the reduction of esters at temperatures of about 0 °C. Thus, lithium tri-f-butoxyaluminum hydride readily reduces phenyl esters of carboxylic acids to aldehydes in 33-77% yields other esters are reported to be unreactive, as are many other functional groups (acyl chlorides react with the same reagent at -70 °C, however). Phenylbenzoate and phenyl cyclopropanecarboxylate do not give the aldehyde. Iminium salt esters (11 equation 4) can be reduced with lithium tri-f-butoxyaluminum hydride (see Section 1.11.3). ... 

Selective reduction of ketones. Selective reduction of a ketone in the presence of an aldehyde is possible by selective reaction of the aldehyde with t-butylamine (4 A molecular sieves), reduction of the ketone with lithium tri-f-butoxyaluminum hydride, and, finally, cleavage of the aldimine to the aldehyde with aqueous HCl. The three-step sequence can be conducted in one pot. The selectivity is high. The method is not applicable to conjugated ketones because of conjugate reduction. 

Lithium tri-f-butoxyaluminum hydride (Lithium aluminum tri-f-butoxyhydride), 1, 620-625 2, 251-252 3, 188. 

For effecting oxidative cyclizations of the types noted, superior results have been obtained with use of the combination lead tetraacetate-iodine, a method introduced by the Ciba-Basel group Ch. Meystre, Heusler, Kalvoda, P. Wieland, Anner, and Wettstein. Known as the hypoiodite reaction because the combination generates HOI, the method appears to be simpler and more efficient than lead tetraacetate alone, and than any of three other methods not employing lead tetraacetate. An improved procedure is as follows. Pregnenolone acetate (5) is first reduced with lithium tri-f-butoxyaluminum hydride in tetrahydrofurane to 3 8-acetoxy-20 -hydroxy-A -pregnene (6) the 20a-isomer is formed in minor amount. At the end... 

Tamm found the reagent useful for reduction of carbonyl groups in the bufadien-olide series. Thus reduction of the ketone (11) with sodium borohydride suffered from the fact that the unsaturated lactone ring is attacked to some extent and the yield of (12) was only 40-50%. Reduction with lithium tri-f-butoxyaluminum hydride in tetrahydrofurane at 0° proceeded rapidly (15 min.), the lactone ring was... 

After reduction of cholestenone with lithium tri-f-butoxyaluminum hydride, Burgstahler and Nordin hydrolyzed the organometallic complex by treatment with ice, sodium hydroxide, and Rochelle salt. 

Acetyl- and 5-formylisothiazoles are readily available from 5-lithioisothiazoles.71,102 However, 3-methyl-4-nitroisothiazole does not form a lithium derivative,72 and 4-formyl-3-methyl-4-nitro-isothiazole was prepared by reduction of the appropriate acid chloride with lithium tri-f-butoxyaluminum hydride.140 A 5-formyl-4-hydroxy-isothiazole has been prepared by direct ring synthesis [Eq. (12)].29... 

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