Chemoenzymatic Total Synthesis of (+)-Oxycodone from Phenethyl Acetate

The stereoselective total synthesis of unnatural (+)-oxy­codone from phenethyl acetate is described. Absolute stereochemistry was established via microbial dihydroxylation of phenethyl acetate with the recombinant strain JM109 (pDTG601A) to the corresponding cis -cyclohexadienediol­ whose configuration provides for the absolute stereo­chemistry of the ring C of (+)-oxycodone. Intramolecular Heck cyclization was employed to establish the quaternary carbon at C-13, along with the dibenzodihydrofuran functionality. The C-14 hydroxyl was installed via SmI 2 -mediated radical cyclization. The synthesis of (+)-oxy­codone was completed in a total of 13 steps and an overall yield of 1.5%. Experimental and spectral data are provided for all new compounds.