Process for the synthesis of substituted morphinans

1. A process comprising the steps:

Step 1: reacting a compound having the structure

with 1,2-ethanediol to obtain a compound having the structure

Step 2: reacting the product of step 1 with a triflating agent to produce a compound having the structure

and

Step 3: reacting the product of step 2 with a source of cyanide ions in the presence of a palladium catalyst, to produce a compound having the structure

2. The process of claim 1 , further comprising the step:

Step 4: hydrolyzing the product of step 3 to produce a compound having the structure

3. The process of claim 2 , further comprising the step:

Step 5: converting the dioxalane group of the product of step 4 to a carbonyl group to produce a compound having the structure

4. The process of claim 3 , wherein step 5 is conducted in the presence of a Brönsted or a Lewis acid.

5. The process of claim 4 , wherein said acid is a mineral acid or a reagent selected from indium (III) trifluoromethanesulfonate, erbium, triflate, cerium (III) triflate, sodium tetrakis(3,5-trifluoromethylphenyl)borate and iodine.

6. The process of claim 5 , wherein said acid is hydrochloric acid.

7. The process of claim 3 , further comprising the step:

Step 6: reducing the product of step 5, thereby producing a compound having the structure

8. The process of claim 7 , wherein step 6 is carried out in the presence of zinc and ammonium chloride.

9. The process of claim 1 , wherein step 1 is conducted in the presence of a Brönsted or a Lewis acid catalyst.

10. The process of claim 9 , wherein said catalyst is selected from p-toluenesulfonic acid, tetrabutylammonium tribromide, zirconium tetrachloride and iodine.

11. The process of claim 1 , wherein step 2 is conducted in the presence of a base catalyst.

12. The process of claim 11 , wherein the base catalyst is selected from diisopropylethylamine, pyridine, N,N-dimethylaminopyridine, triethylamine and 2,6-di-t-butyl-4-methylpyridine.

13. The process of claim 1 , wherein the triflating agent is selected from 4-nitrophenyltriflate, N-phenyl bis(trifluoromethanesulfonimide), trifluoromethanesulfonic anhydride (triflic anhydride) and triflyl chloride.

14. The process of claim 13 , wherein the triflating agent is triflic anhydride.

15. The process of claim 1 , wherein the source of cyanide ions is zinc cyanide.

16. The process of claim 1 , wherein the palladium catalyst is selected from tetrakis(triphenylphosphine)palladium and tris(dibenzylideneacetone)dipalladium.

17. The process of claim 1 , wherein the palladium catalyst comprises a ligand selected from 1,1′-bis(diphenylphosphino)ferrocene (DPPF), 1,3-bis(diphenylphosphino)propane (DPPP), triphenylphosphine, 1,3-bis(diphenylphosphino)propane, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos).