Lithium aluminum deuteride reduction with

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.)... 

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... 

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. 

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... 

The etereochemically speoifio character of lithium aluminum hydride reduction was first indicated by the conversion of bww-2,3-1 posybutane into optically active 2-butanol (Eq. 377), reported by Lopoux and Lucas,1007 and conducted recently in the same manner with lithium aluminum deuteride by Helmkamp and Schnaute. ... 

Primary and secondary alcohols can be converted to alkanes by conversion to tosylates followed by reduction with LAH. This reduction is valuable because deuterium can be easily introduced into the alkane by the use of lithium aluminum deuteride (LAD) instead of LAH. 

Ascarylose (94) and the (35) deuterium-labeled ascarylose were prepared starting from methyl a-L-rhamnopyranoside via the 2,3-anhydro sugar 120 (Scheme 34).204 Opening of the epoxide ring with lithium aluminum hydride in THF led selectively to the 3-deoxy derivative. If reduction was performed with lithium aluminum deuteride, the methyl (3S)-[32H]ascaryloside (3S)-[32H]119 was obtained. 

A stereospecific reduction of a pseudoglycal has been used to prepare the same isomer.23 Reduction of methyl 4,6-0-benzylidene-2,3-dideoxy-/3-D-erythro-hex-2-enopyranoside (6) with lithium aluminum deuteride led to the stereospecific synthesis of 4,6-0-benzylidene-3-deoxy-D-glucal-3(S)-d (7), which, after oxidation with osmium tetra-oxide-periodate followed by debenzylidenation, gave 2-deoxy-D-erythro-Tpentose-2(S)-d (2-deoxy-2-deuterio-D-arabinose) (8). Reduc-... 

Reduction of 3-O-benzyl-1,2-O-isopropylidene-a-D-xylo-pento-dialdo-l,4-furanose (23) with lithium aluminum deuteride, followed by catalytic debenzylation, gave an unequal R and S mixture (24) of 1,2-O-isopropylidene-a-D-xylofuranoses-S-d that was converted into a mixture (25) of tetra-0-acetyl-/3-D-xylopyranose-(R)- and (S)-5-d. Inspection of the p.m.r. spectrum showed, for the C-5 proton, two signals that were doublets, with splittings of 4.2 and 8.1 Hz, corresponding to a,e and a,a coupling, respectively, with the axial proton at C-4. 

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