Stereoselective reduction of a morphinone

1. A synthetic method comprising:

stereoselectively reducing a ketone of a morphinone to a hydroxyl using a reducing agent selected from the group consisting of potassium tri-sec-butylborohydride and sodium tri-sec-butylborohydride to form a reduced morphinone, wherein the morphinone and the reduced morphinone have the following structures:

 respectively,

wherein R 1 is H or a hydroxyl protecting group; and

wherein the synthetic method has a conversion yield of 85% or greater of the ketone to the hydroxyl, and 99% or greater of the reduced morphinone is in an α epimer form.

2. The method of claim 1 , wherein R 1 is H.

3. The method of claim 1 , wherein R 1 is a hydroxyl protecting group selected from the group consisting of alkanoyl having 2 to 5 carbons; aryloyl having 7 to 11 carbons, benzyl, 1 ethoxyethyl, methoxymethyl, 4-methoxyphenylmethyl, methoxyethoxymethyl, 1 ethoxyethyl, benzyloxymethyl, (β trimethylsilylethoxy)methyl, tetrahydropyranyl, 2,2,2 trichloroethoxycarbonyl, t butyl(diphenyl)silyl, trialkylsilyl, trichloromethoxycarbonyl and 2,2,2-trichloroethoxymethyl.

4. The method of claim 3 , wherein R 1 is methoxyethoxymethyl.

5. The method of claim 1 , wherein the conversion yield is at least 95%.

6. The method of claim 5 , wherein the conversion yield is at least 98%.

7. The method of claim 1 , wherein the stereoselective reduction is performed in a solvent of tetrahydrofuran.

8. The method of claim 1 , wherein the reducing agent is potassium tri-sec-butylborohydride.