ALKOXYALUMINATE REDUCING AGENTS

These relatively mild reducing agents can reduce the carbonyl of a lactone to give a lactol. In one example, 75 (an intermediate in Magnus synthesis of grandisol) was isolated in 97% yield when 74 was reduced with lithium triethoxyaluminum hydride at -20°C. It is known that trialkoxyaluminum hydrides will reduce aldehydes, ketones, esters and acid chlorides before reducing nitriles and amides. 

Lithium diethoxyaluminum hydride [LiAlH2(OEt)2] and the monoethoxy derivative [LiAlH3(OEt)] have been used in syntheses. It is clear, however, that LiAlH(Ot-Bu)3 is one of the more commonly used reagents. It is stable in solution, gives useful concentrations in ether solvents (36 g/100 g of solvent in THE, 

2 g/100 g in diethyl ether and 41 g/100 g in diglyme), and reacts with organic substrates faster in solutions where it is in higher concentration. It is also thermally stable. Heating to 165°C for five h. followed by titration with acid showed that 92% of its active hydrogen was retained. It is apparent that lithium tri-terf-butoxyaluminum hydride is less reactive than the other alkoxyaluminum hydrides discussed (see above), but it easily reduces aldehydes, ketones, some esters, anhydrides, and acid chlorides. Epoxides are reduced very slowly nitriles and dimethyl amides are not reduced at all. The use of this reagent is a preferred method for the selective reduction of acid chlorides to aldehydes. The best yields of aldehydes are realized 

Reaction of conjugated carbonyls with LiAlH(Ot-Bu)3 gives primarily 1,2-reduction, as in the quantitative reduction of 78 to 79 in Marshall s synthesis of globulol. goth sulfonate esters such as the mesylate group in 78, and halides are resistant to reduction with LiAlH(Of Bu)3. 

Red-Al behaves as a base in certain applications, /fa readily reducible functional group is not present in the molecule. Kametani used Red-Al to induce a Steven s rearrangement (sec. 8.8.C.ii) of berbine methiodide (88) to spirobenzylisoquinoline (89) (9.4%) plus 90 (22.5%). 3 The yield of rearranged products was poor, which is typical for this application of Red-Al. 

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