Methods for stereoselective reduction

1. A method of reducing the C—C double bond of an enone of a steroidal compound to produce a mixture of β ketone product and α ketone product, the method comprising treating a solution or suspension of the steroidal compound in a solvent with hydrogen gas in the presence of a catalyst and a substituted pyridine.

2. The method of claim 1 , wherein an excess of the β ketone product is produced compared to the α ketone product.

3. The method of claim 1 , wherein the ratio of the β ketone product to the α ketone product is at least 2:1.

4. The method of claim 1 , wherein the ratio of the β ketone product to the α ketone product is at least 10:1.

5. The method of claim 1 , wherein the ratio of the β ketone product to the α ketone product is at least 20:1.

6. The method of claim 1 , wherein the ratio of the β ketone product to the α ketone product is at least 50:1.

7. The method of claim 1 , wherein the substituted pyridine is a 3-substituted pyridine.

8. The method of claim 7 , wherein the 3-substituted pyridine is selected from 3-picoline, 3-methoxypyridine, 3-ethylpyridine, 3-n-butylpyridine, 3-isobutylpyridine, 3-hydroxypyridine, 3-aminopyridine, and 3-dimethylaminopyridine.

9. The method of claim 7 , wherein the 3-substituted pyridine is 3-picoline.

10. The method of claim 1 , wherein the catalyst is a palladium catalyst.

11. The method of claim 1 , wherein the solvent comprises the substituted pyridine.

12. The method of claim 11 , wherein the solvent comprises 3-picoline.

13. A method of making a mixture of compounds of formulae II and III:

or a pharmaceutically acceptable salt thereof, wherein:

n is 0 or 1;

R 30 is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl, haloalkyl, —OR 31 , —C(O)R 31 , —CO 2 R 31 , —SO 2 R 31 , —C(O)N(R 31 )(R 31 ), —[C(R) 2 ] q —R 31 , —[(W)—N(R)C(O)] q R 31 , —[(W)—C(O)] q R 31 , —[(W)—C(O)O] q R 31 , —[(W)—OC(O)] q R 3 , —[(W)—SO 2 ] q R 31 , —[(W)N(R 31 )SO 2 ] q R 31 , —[(W)—C( O)N(R 31 )] q R 31 , —[(W)—O] q R 31 , —[(W)—N(R)] q R 31 , —W—(NR 31 ) 3 + X − or —[(W)—S] q R 31 ;

W, at each occurrence, independently is an alkylene group;

q, at each occurrence, independently is 1, 2, 3, 4, 5, or 6;

X − is a halide;

R 31 , at each occurrence, independently is H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, aralkyl, heteroaryl, heteroaralkyl or —[C(R) 2 ] p —R 32 ;

or any two occurrences of R 31 taken together with the atom to which they are bound form an optionally substituted 4-8 membered ring that contains 0-3 heteroatoms selected from N, O and S;

p is 0-6;

each R 32 is independently

hydroxyl, —N(R)COR, —N(R)C(O)OR, —N(R)SO 2 (R), —C(O)N(R) 2 , —OC(O)N(R)(R), —SO 2 N(R)(R), —N(R)(R), —COOR, —C(O)N(OH)(R), —OS(O) 2 OR, —S(O) 2 OR, —OP(O)(OR)(OR), —NP(O)(OR)(OR), or —P(O)(OR)(OR); and

each R is independently H, alkyl, alkenyl, alkynyl, aryl, cycloalkyl or aralkyl;

the method comprising treating a solution or suspension of compound of formula IV:

or a pharmaceutically acceptable salt thereof, in a solvent with hydrogen gas in the presence of a catalyst and a substituted pyridine.

14. The method of claim 13 , wherein an excess of the compound of formula II is produced compared to the compound of formula III.

15. The method of claim 13 , wherein the ratio of the compound of formula II to compound of formula III is at least 10:1.

16. The method of claim 13 , wherein the ratio of the compound of formula II to compound of formula III is at least 20:1.

17. The method of claim 13 , wherein the substituted pyridine is a 3-substituted pyridine.

18. The method of claim 17 , wherein the 3-substituted pyridine is 3-picoline.

19. The method of claim 13 , wherein the solvent comprises the substituted pyridine.

20. The method of claim 19 , wherein the solvent comprises 3-picoline.

21. The method of claim 13 , wherein the catalyst is a palladium catalyst.

22. The method of claim 13 , wherein n is 1.

23. The method of claim 22 , wherein R 30 is H.

24. The method of claim 13 , wherein the compounds of formulae II and III have the following absolute chemistry: