REGIOCHEMICAL CONTROL IN DIHYDROPHENANTHRENE SYNTHESIS - PHOTO-CHEMICAL TOTAL SYNTHESIS OF JUNCUSOL

Three approaches are described toward the total synthesis of juncusol, l, 6-dimethyl-5-vinyl-2, 7-dihydroxy-9, 10-dihydrophenanthrene (1), a cytotoxic constituent of the needlerush Juncus roemerianus. Wittig condensation of the phosphonium salt derived from 2-methyl-3-methoxybenzyl bromide with 3-methoxy-4-methyl-5-cyanobenzaldehyde gave the mixture of E and Z cyanostilbenes 13. Reduction of this mixture gave the corresponding diarylethane, which failed to undergo oxidative aryl-aryl cyclization. Photocyclization of the above stilbenes proceeded readily to give a 7: 1 ratio of the two expected phenanthrenes in which the unwanted 7-cyano regioisomer 17 predominated. The Ziegler modification of the Ullmann coupling was used to prepare the symmetrical dialydehyde 43, which was converted by Wittig reagent to the vinyl aldehyde 44 and ultimately reduced to key intermediate 47. Photocyclization of the latter gave the dihydrophenanthrene alcohol 48 which was converted via the aldehyde 46, Wittig homologation, and demethylation to juncusol. The overall yield of the latter from 2-methyl-3-methoxybenzaldehyde is 18% over ten steps; the route provides the first total synthesis of this natural product. © 1979, American Chemical Society. All rights reserved.