Lithium aluminum deuteride reduction

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. ... 

Deuteration at C-3 by Lithium Aluminum Deuteride Reduction of 5a.-Pregnane-3,20-dione 3-Tosylhydrazone 20-Ethylene keta ... 

Some advantages of this reaction are high yield if the tosylate is in a sterically accessible position excellent isotopic purity of the product (usually higher than-95%) and perhaps most important, access to stereospecifically labeled methylene derivatives. For example, deuteride displacement of 3j -tosylates (183) yields the corresponding Sa-d derivative (185) in 96-98% isotopic purity. Application of this method to the labeled sulfonate (184), obtained. by lithium aluminum deuteride reduction of a 3-ketone precursor (see section HI-A) followed by tosylation, provides an excellent synthesis of 3,3-d2 labeled steroids (186) without isotopic scrambling at the adjacent positions. The only other method which provides products of comparable isotopic purity at this position is the reduction of the tosyl-hydrazone derivative of 3-keto steroids (section IV-B). 

Lithium aluminum deuteride reduction of the 2a,3a-oxide function has been carried out with a number of different 5a-steroids (227). ° The isotopic purity of the resulting 2 -d,-3a-ols (228) is usually 96-100%. By mild oxidation, under Jones conditions, these alcohols can be converted into stereospecifically labeled monodeuterio ketones (229) ° of high isotopic purity. (For an alternate preparation of certain a-monodeuterio ketones, see section VI-B.)... 

Deuteration at C-3 by lithium aluminum deuteride reduction of 5a-pregnane-3, 20-dione 3-tosylhydrazone 20-ethylene ketal, 177... 

The reduction of tosylhydrazones can also be performed with sodium borodeuteride in boiling methanol or dioxane, but the mechanism of this reaction (in boiling dioxane at least) is radically different from that of the lithium aluminum deuteride reductions.82 With sodium borohydride the first step is apparently hydride attack on the carbon atom of the C=N bond which is probably concerted with the elimination of the tosylate anion (110 - 111). Migration of the hydrogen from nitrogen to C-3 in (111) concerted with expulsion of nitrogen, provides the corresponding methylene derivative (100).82... 

Liquid-gas phase exchange, 158 Lithium aluminum deuteride, 162, 199 Lithium aluminum deuteride reduction, 177, 178... 

Oxidation of dianhydrohexopyranoses with ruthenium tetraoxide yields all four possible keto-epoxides469 these can be readily transformed into the 3-deoxy ketones459 (see Sect. VII,3,b). The same agent oxidizes l,6-anhydro-2,3-di-0-benzoyl-/3-D-glucopyranose52 (89). The selectivity of the lithium aluminum deuteride reduction of the glycos-... 

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. 

As a general procedure, a mixture of the steroidal ketone (50 mg) and lithium aluminum deuteride (20 mg) in dry ether (5 ml, freshly distilled from lithium aluminum hydride) is heated under reflux until the reduction is complete according to thin layer chromatography test. The excess deuteride is then decomposed by the careful addition of a few drops of water and the reaction mixture is worked up by the usual procedure. For hindered ketones or esters the use of other solvents, such as tetrahydrofuran or dioxane, may be preferable to allow higher reaction temperatures. 

During the course of these mechanistic studies a wide range of possible applications of this reaction have been revealed. When the reduction is carried out with lithium aluminum deuteride and the anion complex decomposed with water, a monodeuterio compound (95) is obtained in which 70% of the deuterium is in the 3a-position. Reduction with lithium aluminum hydride followed by hydrolysis with deuterium oxide yields mainly (70 %) the 3j5-di-epimer (96), while for the preparation of dideuterio compounds (94) both steps have to be carried out with deuterated reagents. ... 

Deuteration at C-3 by Reduction of 5a.-Androstan-3-one Oxime with Lithium Aluminum Deuteride... 

Deuterium labeling of C-18 has also been accomplished by an alternate procedure adapted from the Nagata steroid synthesis. During the course of the total synthesis of pregnanolone, thevC-18 function is introduced in the form of a nitrile group. Reduction of this function in intermediate (247) with lithium aluminum deuteride leads to a deuterated imine (248), which upon Wolff-Kishner reduction and acid-catalyzed hydrolysis... 

Deuteration at C-3 by reduction of 5o -androstan-3-one oxime with lithium aluminum deuteride, 178... 

Deuteration at the 6/3-position by reduction of a 6a, 7a-oxido steroid with lithium aluminum deuteride, 205... 

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

Reduction of 5//-6,7-dihydrodibenz[t, e]azepine-5,7-dione (31) with lithium aluminum deuteride followed successively by ring chlorination with N-chlorosuccinimide and dehydrochlorination. affords [5,5,7-2H3]-5//-dibenz[r, >]azepine (32).117... 

Deuteration by reduction with lithium aluminum deuteride, 205 Deuteration of a diterpene, 170 Deuteration of double bonds, 179 Deuteration of estradiol, 157 Deuteration of 5a-pregn-9-en-12-one, 155 Deuteration with deuteriodiborane and hydrogen peroxide, 193... 

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