Reduction with metal deuteride complexes

The isotopic purity of the products from a lithium aluminum deuteride reduction is usually equivalent to that of the reagent. The presence of moisture has little effect on the isotope composition of the products, causing only the decomposition of some of the reagent. For the best results, however, it is advisable to distill the solvent— usually ether, tetrahydrofuran or dioxane depending on the desired reaction temperature—from lithium aluminum hydride directly into the reaction flask. In this manner the reduction of 3-keto-5a-steroids (60), for example, gives the corresponding 3a-di alcohols (61) in 98% isotopic purity.  

A much more stereoselective and milder reducing agent is lithium tri-r- 

The reduction of the 16-keto function in kryptogenin (66) is a good example for the selectivity of sodium borodeuteride. The resulting 16a-di-16y -hydroxy analog (67) can then be cyclized to give a Iba-d -spirostane derivative (68).  

Reduction of Steroidal Ketones with Lithium Aluminum Deuteride 

This reaction does not need any special handling and the reduction conditions commonly used witli lithium aluminum hydride (see chapter 2) are equally applicable with lithium aluminum deuteride. 

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Reduction with metal deuteride complexes (section Ill-A) is undoubtedly the most convenient way to convert carbonyl compounds into the corresponding deuterated alcohols. For stereochemical reasons, however, it is sometimes necessary to resort to reductions with alkali metals in O-deuterated alcohols, or in liquid deuterioammonia-O-deuterioalcohol mixtures. 

Deuteration with metal deuteride complexes reduction of steroidal ketones with lithium aluminum deuteride, 164 Dimethyl sulfoxide dicyclohexylcarbo-... 

Deuterated isobenzofurans are also available. Reduction of phthalides with complex metal deuterides yields hydroxyphthalans, which can be converted to the corresponding isobenzofurans (84T4597 85CJC735, 85JOC5902). 

There are a few examples of hydroxyl group participation in reductions by complex metal hydrides. Franzus and Snyder " report that reduction of norbornadiene-7-ol (258) or its acetate with lithium aluminum hydride results only in reductive formation of (2nti-7-norbornenol. Use of LiAlD4 and H2O work-up yields a single deuterium incorporation in an exo position. D2O work-up leads to the incorporation of a second xo-deuterium. The reaction was thus formulated to occur as shown in Scheme 12. Borden has published studies that indicate that the step (259)-(260) occurs with intramolecular deuteride attack. 

Addition of deuterium to carbonyl double bonds and their nitrogen analogs is accomplished by complex metal hydrides in an increasing number of examples. In this reduction two deuterium atoms are transferred of course, only the deuterium on carbon is firmly bound, and that attached to the hetero atom can be removed in the usual way. Since such reactions can in general be carried out with LiAlD4 in aprotic solvents, the use of lithium aluminum deuteride, LiAlH4,. offers no peculiarities. The necessary LiAlD4, which is extremely sensitive to hydrolysis, is commercially available. It can be conveniently handled as a solution in a dry dialkyl ether or in tetrahydrofuran at temperatures up to ca. 130°. 

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