Lithium tri-t-butoxyaluminium hydride

Sterically bulky reducing agents, e.g. lithium tri-t-butoxyaluminium hydride, can selectively reduce acid chlorides to aldehydes at low temperatures (—78 °C). Lithium tri-t-butoxyaluminium hydride, LiAlH(0-t-Bu)3, has three electronegative oxygen atoms bonded to aluminium, which makes this reagent less nucleophilic than LiAlH4. 

The reaction of umbellulone (215) with JV-bromosuccinimide has been examined. Umbellulone is a hindered ketone, and Wheeler and Chung have shown that while lithium aluminium hydride in ether yields the expected mixture of the two umbellulols (216) and (217), a more bulky nucleophile like lithium tri-t-butoxyaluminium hydride leads almost exclusively to reduction of the double bond to give (218). ... 

Removal of the 2)3-OH from crustecdysone by reduction of the 2 -tosylate (128) first with lithium tri-t-butoxyaluminium hydride— (129) and then with lithium... 

Starting from 6-methoxynaphth-2-oic acid (64), the 1,2,3,4,5,8-hexahydro-derivative (65) was prepared by reduction with excess lithium and t-butyl alcohol in liquid ammonia. Compound (65) was converted into the keto-acid (66) by hydrolysis. Reduction of (66) with lithium tri-t-butoxyaluminium hydride gave the hydroxy-acid (67). The acetate derivative (68) was converted into the acid chloride (69) by reaction with oxalyl chloride in pyridine. Treatment of this compound with diazomethane afforded the diazoketone (70). Decomposition of the latter with copper powder in cyclohexane gave the cyclopropyl ketone (71) in yields of 70—80%. The acetate function was then hydrolysed, and the resulting hydroxy-ketone (72) was oxidized to the cyclopropyl diketone (73) with Jones reagent. Treatment of (73) with a weakly acidic acetone solution or adsorption on to basic alumina produced the enedione (74) via a retrograde... 

Lithium tri-t-butoxyaluminium hydride is a much milder reducing agent than lithium aluminium hydride. Thus, although aldehydes and ketones are reduced normally to alcohols, carboxylic esters and epoxides react only slowly, and halides, nitriles and nitro groups are not attacked. Aldehydes and ketones can therefore be selectively reduced in the presence of these groups. For example, the aldehyde 93 is reduced selectively to the alcohol 94 (7.73). 

One of the most useful applications of the alkoxy reagents is in the preparation of aldehydes from carboxylic acids by partial reduction of the acid chlorides or dialkylamides. Acid chlorides are readily reduced with lithium aluminium hydride or with sodium borohydride to the corresponding alcohols, but with one equivalent of lithium tri-t-butoxyaluminium hydride, high yields of the aldehyde can be obtained, even in the presence of other functional groups (7.74). 

Several syntheses are available to the 13,14-dihydroprostaglandins, some of which are metabolites of the E and F series. The first of these routes [143, 144] started from the formyl derivative (LVII) of the enol ether of cyclo-pentan-l,3-dione which on reaction with ethyl 6-bromosorbate and tri-phenylphosphine followed by selective catalytic reduction afforded the ester (LVIII). A second formylation followed by elaboration with n-hexanoyl-methylenetriphenylphosphonium chloride 1 to the ketone (LIX) which on reduction of the exocyclic double bond and acid-catalysed solvolysis in benzyl alcohol afforded the benzyl ether (LX) and its isomeric enol ether. Reduction with lithium tri-t-butoxyaluminium hydride to the corresponding 15-hydroxy-compound and palladium-charcoal catalysed hydrogenolysis followed by prolonged catalytic hydrogenation with rhodium-charcoal led to ( )-dihydro-PGEi ethyl ester. 

Di-isobutylaluminium hydride (DIBAL) reduces acid imidazolides to aldehydes in high yields this method has been successfully applied to the synthesis of a-amino-aldehydes from a-amino-acids/ Similarly the acid thiazolidine derivatives (11), which are also readily obtained from carboxylic acids, are reduced by either DIBAL or lithium tri-t-butoxyaluminium hydride to the corresponding aldehyde." ... 

Yamataka, H. Hanafusa, T. J. Org. Chem. 1988, 53, 111. A kinetic. study of the addition of lithium tri-/-butoxyaluminium hydride to alkylcyclohexanones and p,p -disubstituted benzophe-nones has found support for a four-centred transition state which, unlike borohydride addition, is allowed by utilization of the orbitals on aluminium [44]. 

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