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 C(2)-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.
Trauner
Dirk
D
Institut für Organische Chemie, Universität Wien, Währingerstrasse 38, A-1090 Vienna, Austria, and Institut für Organische Chemie, Johann Wolfgang Goethe-Universität, Marie-Curie-Strasse 11, D-60439 Frankfurt, Germany.
Bats
Jan W.
JW
Werner
Andreas
A
Mulzer
Johann
J