Synthesis of enantiomerically pure morphine alkaloids: The hydrophenanthrene route

A concise, linear, total synthesis of (-)-dihydrocodeinone - a close synthetic precursor of (-)-codeine and (-)-morphine - has been achieved. The carbocyclic core of the alkaloid was provided in the form of a phenanthrenone, which was resolved by chromatography on cellulose triacetate. A cuprate conjugate addition was used to establish the crucial benzylic quaternary stereocenter and to introduce the C₂-side chain. Dimeric byproducts provide evidence for a single electron transfer (SET) mechanism. Unusual S(N)2 and radical cyclizations were employed for the formation of the dihydrobenzofuran and the piperidine ring, respectively.