Design for Morphine Alkaloids by Intramolecular Heck Strategy: Chemoenzymatic Synthesis of 10-Hydroxy-14-epi-dihydrocodeinone via C-D-B Ring Construction

Abstract

Enzymatic dihydroxylation of β-bromoethylbenzene provided a homochiral diene diol that served as starting material for the synthesis of the complete morphinan skeleton via an intramolecular Heck cyclization.

Key words

enzymatic dihydroxylation - Heck reaction - Mitsunobu reaction - Friedel-Crafts reaction - morphinans

References and Notes

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19

For the description of model studies see ref. 1a.

25

It is likely that the hydrogenation of neopine-type compounds only proceeds to the natural configuration at C-14 in systems containing the full phenanthrene core, which is not the case with 14 or 15. The scarcity of material precluded us from performing the C-10-C-11 closure prior to hydrogenation.