Method for catalytic preparation of hydromorphone and hydrocodone

1. A method of transforming morphine to hydromorphone or codeine to hydrocodone in the presence of a compound of formula (III):

[M(P(R a )(R b )N(R c )(R d )) 2 X n ] m Y p

wherein M is Rh or Ir;

each R a , R b , R c and R d is independently H, optionally substituted alkyl, aryl, heterocyclic, or cycloalkyl;

each X is independently H, —OH, halo, alkoxide, aryloxide, an anion or a solvent molecule;

Y is an anion; n is 0 or 1; m is 1 or 2; and p is 0, 1 or 2.

2. The method of claim 1 wherein

M is Rh;

each R a , R b , R c and R d is independently selected from H, C 1-8 alkyl optionally substituted with halo or —OH; and aryl, heterocyclic, or cycloalkyl; each optionally substituted with halo, —OH or alkyl; and

each X is independently H, OH or halide.

3. A method of transforming morphine to hydromorphone or codeine to hydrocodone in the presence of a compound of the formula:

wherein M is Rh or Ir;

each X is independently H, —OH, halo, alkoxide, aryloxide, an anion or a solvent molecule;

R 1 , R 2 , R 5 , R 6 , R 9 , R 10 , R 13 and R 14 are independently selected from H and optionally substituted aryl, heterocyclic, or cycloalkyl;

R 3 , R 4 , R 7 , R 8 , R 11 , R 12 , R 15 and R 16 are independently selected from H and optionally substituted alkyl; or

R 4 and R 8 , and R 12 and R 16 form an optionally substituted cycloalkyl, heterocyclic, or aryl ring system.

4. The method of claim 3 wherein

R 1 , R 2 , R 5 , R 7 , R 9 , R 10 , R 13 and R 14 are independently selected from H and aryl, heterocyclic, or cycloalkyl, each optionally substituted with halo, —OH or C 1-4 alkyl;

R 3 , R 4 , R 6 , R 8 , R 11 , R 12 , R 15 and R 16 are independently selected from H, C 1-8 alkyl optionally substituted with halo or —OH; or

R 4 and R 8 , and R 12 and R 16 form an cycloalkyl, heterocyclic or aryl ring system comprising C, N, S and O; said ring system optionally substituted with halo, —OH or C 1-4 alkyl.

5. The method of claim 4 wherein R 1 , R 2 , R 5 , R 6 , R 9 , R 10 , R 13 and R 14 are independently selected from H or C 5-6 aryl, optionally substituted with halo, —OH or C 1-4 alkyl.

6. The method of claim 4 wherein R 3 , R 4 , R 7 , R 8 , R 11 , R 12 , R 15 and R 16 are H or C 1-8 alkyl optionally substituted with halo or —OH.

7. The method of claim 4 wherein R 4 and R 8 , and/or R 12 and R 16 form an cycloalkyl, heterocyclic or aryl ring system comprising atoms selected from C, N, S and O; said ring system optionally substituted with halo, —OH or C 1-4 alkyl.

8. The method of claim 7 wherein each of R 4 and R 8 , and R 12 and R 16 form an cycloalkyl, heterocyclic or aryl ring system comprising 3 to 8 atoms selected from C, N, S and O; said ring system optionally substituted with halo, —OH or C 1-4 alkyl.

9. The method of claim 8 wherein each of R 4 and R 8 , and R 12 and R 16 form an cycloalkyl, heterocyclic or aryl ring system comprising 5 to 6 atoms selected from C, N, S and O; said ring system optionally substituted with halo, —OH or C 1-4 alkyl.

10. The method of claim 9 wherein each of R 4 and R 8 , and R 12 and R 16 form an cycloalkyl ring system comprising 5 to 6 C atoms; said ring system optionally substituted with halo, —OH or C 1-4 alkyl.

11. A method for transforming morphine to hydromorphone or codeine to hydrocodone comprising reacting a compound of the formula [ClRh(C 2 H 4 ) 2 ] 2 or [ClRh(COE) 2 ] 2 with a compound of the formula P(R a )(R b )N(R c )(R d ); wherein each R a , R b , R c and R d is independently selected from H, optionally substituted alkyl; and optionally substituted aryl, heterocyclic, or cycloalkyl; COE is cyclooctene; and adding the resulting product to a solution containing morphine or codeine; and reacting the mixture to transform morphine to hydromorphone or codeine to hydrocodone.