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Article

Enantioselective Synthesis of (−)-Dihydrocodeinone: A Short Formal Synthesis of (−)-Morphine¹^,^†

Supporting Info

Kathlyn A. Parker*^‡ and Demosthenes Fokas^§

Department of Chemistry, Brown University, Providence, Rhode Island 02912

J. Org. Chem., 2006, 71 (2), pp 449–455

DOI: 10.1021/jo0513008

Publication Date (Web): November 4, 2005

†

This paper is dedicated to the memory of Arthur G. Schultz.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

‡

Current address: Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York 11794-3400.

Current address: Department of Chemistry, ArQule Inc., 19 Presidential Way, Woburn, MA 01801. E-mail: dfokas@arqule.com.

, kparker@notes.cc.sunysb.edu

Abstract

The radical cyclization approach to the morphine alkaloids has been applied in an asymmetric synthesis of (−)-dihydrocodeinone. A chiral cyclohexenol (R-32), from the CBS reduction of the enone, is the source of chirality. The first key step, tandem closure in which stereochemistry is controlled by geometric constraints, (−)-15b → (+)-16, was followed by an unprecedented reductive hydroamination, completing the synthesis of (−)-dihydroisocodeine ((−)-17) in 13 steps from commercially available materials.

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Published In Issue January 20, 2006
Received June 24, 2005

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Article

Enantioselective Synthesis of (−)-Dihydrocodeinone: A Short Formal Synthesis of (−)-Morphine¹^,^†