Oxirane reduction with lithium aluminum hydride

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

Reductive opening of the oxirane ring of 188 with lithium aluminum hydride, and acetylation with acetic anhydride-DMAP, provided the pen-... 

Reductive opening of the oxirane ring of 193 with lithium aluminum hydride, and acetylation, provided compound 194. Epoxidation of 194 with mCPB A gave the epoxide 195. Opening of the oxirane ring with acetate ions, followed by acetylation, gave the tetraacetate 196, or, by exhaustive acetylation with acetic anhydride-DMAP, the pentaacetate 189. Compounds 196 and 189 were readily transformed into 190 by hydrolysis. " ... 

Estradiol and estrone are metabolized to an array of oxidized products, one of which consists of the 16a-hydroxy derivative 30-4. One approach to preparing that compound starts by reaction of estrone with isopropyhdene acetate, to afford the acetate of the enolic form of the ketone and also the ester of the phenol at position 3 (30-1) (Scheme 3.30). Treatment of that product with perbenzoic acid leads to the a-oxirane 30-2, formed from approach of the reagent from the less hindered backside. Acetolysis of that intermediate gives 16a-acetoxyestrone (30-3). Reaction of that product with lithium aluminum hydride leads to reduction of the 17-carbonyl and also the phenolic ester to give the trans-Aio 16a-hydroxy- 17(3-estradiol (30-4). The same product is obtained on reducing 30-2 directly also with lithium aluminum hydride. 

The synthesis of hepialone (928), the principal sex pheromone produced by the male moth Hepaialus californicus, relies on (7 )-1,2-epoxybutane (925) as the source of chirality (Scheme 136) [204]. Epoxide 925 is in turn synthesized from (7 )-malic acid by reduction of the THP derivative 921b with lithium aluminum hydride and conversion of diol 922 to ditosylate 923 and then dibromide 924. Removal of the protecting group followed by base-catalyzed cyclization results in epoxide formation. Debromination of the primary bromide with tri-n-butyltin hydride affords the desired oxirane 925. 

Reductive cyclization by lithium aluminum hydride as the key step has been employed for the preparation of O-benzylated l,6-anhydro-2,3-dideoxy-2,3-epi-mino- and l,6-anhydro-3,4-dideoxy-3,4-epimino-p-D-hexopyranoses having the alio-, manno-, galacto-, and to/o-configurations from suitable 1,6 2,3- and l,6 3,4-dianhydro-p-D-hexopyranoses. Stereoselective trara-diaxial cleavage of the oxirane ring was effected by treatment with sodium azide and ammonium chloride in a 2-methoxyethanol-water mixture at 110-120 °C. Synthesis of 1,6-anhydro-4-(9-benzyl-2,3-dideoxy-2,3-epimino-p-D-marmopyranose (7) from di-anhydro derivative 4 illustrates this methodology. An alternative reduction by sodium borohydride in THF was also tested in the preparation of the 2,3-d-u//o-and D-ma u-epimines in this series. It provided a better yield (73%) than... 

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