Chemoenzymatic Total Synthesis of (+)-Codeine by Sequential Intramolecular Heck Cyclizations via C-B-D Ring Construction

Abstract

An enzymatically generated diene diol was utilized as homochiral starting material in the total synthesis of (+)-codeine featuring a Mitsunobu inversion and two intramolecular Heck ­cyclizations.

Key words

enzymatic dihydroxylation - sequential intramolecular Heck reactions - hydroamination - codeine

References and Notes

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1

To whom correspondence should be addressed.

14

We are very grateful to Dr. Weiping Tang (University of Wisconsin) for supplying us with detailed description of the experiments performed in Trost’s group as well as experimental and spectral information used in monitoring the progress of the reaction. In spite of these details we were never successful in detecting codeine in the reaction mixtures and had to resort to alternative ways of performing the C-9 amination.