Formal Synthesis of (-)-Codeine by Application of Temporary Thio Derivatization

Desymmetrization of a p-quinone monoacetal by organocatalytic sulfa-Michael addition provided rapid access to a C-ring building block for a formal synthesis of (-)-codeine. By means of a diastereoselective 1,2-addition for A/C-ring union, an intramolecular nitrone cycloaddition for construction of the phenanthrene core, and a sulfoxide elimination, an enantiopure key intermediate of the authors' previous synthesis of racemic codeine was available in 12 steps from isovanillin.