[5] Although methods involving stoichiometric amounts of chiral metal hydrides have been supplanted in modern times by enantioselective catalytic reductions, they are of historical interest as early examples of stereoselective reactions.
The tendency to add in a 1,4 sense is correlated with the softness of the hydride reagent according to Pearson's hard-soft acid-base theory.
[7] Experimental results agree with the theory—softer hydride reagents afford higher yields of the conjugate reduction product.
[8] A few substrates, including diaryl ketones,[9] diarylalkenes,[10] and anthracene,[11] are known to undergo reduction by single-electron transfer pathways with lithium aluminium hydride.
Conformationally flexible ketones undergo axial attack by the hydride reagent, leading to the equatorial alcohol.
[17] The preference for axial attack on conformationally flexible cyclic ketones has been addressed by a model put forth by Felkin and Anh.
Alkoxyaluminium and closely related hydride reagents reduce a wide variety of functional groups, often with good selectivity.
Many selective reductions of carbonyl compounds can be effected by taking advantage of the unique reactivity profiles of metal alkoxylaluminium hydrides.
For instance, lithium tri-tert-butoxy)aluminium hydride (LTBA) reduces aldehydes and ketones selectively in the presence of esters, with which it reacts extremely slowly.
Use of relatively unhindered lithium trimethoxyaluminium hydride results in nearly quantitative direct addition to the carbonyl group (Eq.
Pure, solid Red-Al is stable for several hours under inert atmosphere and is available commercially as a 70%-solution in toluene under the trade name Vitride or Synhydrid.
Reduction may typically be carried out in a round-bottom flask equipped with a drying-tube-capped reflux condenser, a mercury-sealed mechanical stirrer, a thermometer, a nitrogen inlet, and an additional funnel with a pressure-equalizing side arm.
The benzene layer was separated, washed with 10 mL of water, dried over potassium carbonate, and concentrated to give the product as a yellow oil in 91% yield (0.480 g); IR (film) 770, 1140, and 1320 cm–1; NMR (CDCl3) δ 4.22 (q, 2 H), 1.61 and 1.59 (2 d, 6 H, J = 7 Hz), 7.3 (s, 4 H); m/e (rel.