Lithium /-butoxy aluminium hydride

Semmelhack et al. chose CuBr, together with either Red-Al or LiAl(OMe)3H in a 1 2 ratio, to afford presumed hydrido cuprates, albeit of unknown composition [llj. In THF, both the former Na complex and the latter Li complex are heterogeneous (and of differing reactivities), yet each is capable of 1,4-reductions of unsaturated ketones and methyl esters (Eq. 5.4). Commins has used a modified version, prepared from lithium tri-t-butoxy-aluminium hydride and CuBr (in a 3 4.4 ratio), to reduce a 3-substituted-N-acylated pyridine regioselectively at the a-site [12]. 

Reduction of unsaturated ketones to saturated alcohols is achieved by catalytic hydrogenation using a nickel catalyst [49], a copper chromite catalyst [50, 887] or by treatment with a nickel-aluminum alloy in sodium hydroxide [555]. If the double bond is conjugated, complete reduction can also be obtained with some hydrides. 2-Cyclopentenone was reduced to cyclopentanol in 83.5% yield with lithium aluminum hydride in tetrahydrofuran [764], with lithium tris tert-butoxy)aluminium hydride (88.8% yield) [764], and with sodium borohydride in ethanol at 78° (yield 100%) [764], Most frequently, however, only the carbonyl is reduced, especially with application of the inverse technique (p. 21). 

The chiral, reactive 2(3// )-quinazolinone 406 underwent diastereoselective reduction with lithium tri(fer7-butoxy)-aluminium hydride at —60°C to generate the 1,4-dihydro derivative 407 <2003JOC754>, while nickel boride reduction of the 2-thioxoquinazoline 408 gave the 2,3-dihydro-4(177)-quinazolinone 409 <2003JHG677>. 

Selective reduction of functional groups can be achieved by chemical modification of the LiALH4 for example, lithium tri(t-butoxy)aluminium hydride [LiAIH(t-OBu)3] is a more selective reagent, and reduces aldehydes and ketones, but slowly reduces esters and epoxides. Nitriles and nitro groups are not reduced by this reagent. Carboxylic acids can be converted into the aldehyde via acid chloride with lithium tri(tert-butoxy) aluminium hydride at a low temperature (—78°C). The nitro compounds are not reduced under this condition. Thus, selective reduction of 3,5-dinitrobenzoic acid (6.45) to 3,5-dinitrobenzaldehyde (6.47) can be achieved in two steps. First, 6.45 is converted into 3,5-dinitrobenzoyl chloride (6.46) and then LiAlH(t-OBu)3 reduction of 6.46 gives 6.47. 

When one of the substituents is a highly polar group (e.g. halogen) Cornforth [13] suggested that the polar group and oxygen atom stay as far apart as possible in order to minimise dipolar interactions for example reduction of 2-chloro-l-deu-tero-2,3,3-trimethylbutanal with lithium di-butoxy aluminium hydride is consistent with this model (Fig. 6-3) [14]. 

Lithium Tri(t-Butoxy)aluminium Hydride Li+ (tBuO)sAlH... 

Zlatoidsky (50) recently described the synthesis of N-protected a-amino aldehydes via reduction of the corresponding phenyl esters by lithium tri(tert-butoxy)aluminium hydride. Since 4-hydroxybenzoic acid is commercially available, we decided to explore this reaction in the soUd phase strategy. 

Lithium aluminium tri-t-butoxy hydride rapidly reduces imidoyl chlorides to imines under very mild conditions/ an improvement over previous methodology. 

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