A regiospecific total synthesis of juncusol (1) based on the use of two consecutive phenol annulations is detailed. A recent search for the antileukemic constituents in the extracts of needle rush, Juncus ~ roemerianus, resulted in the isolation and identification of juncusol (l_), a highly substituted 9,10-dihydrophenanthrene2 possessing modest antitumor and antimicrobial properties. The unusual structure of juncusol (JJ, its confirmed cytotoxic properties, and the notable lack of synthetic methodology capable of easily accommodating the aromatic substitution patterns found in this and related dihydrophenanthrenes have provided the incentive for much synthetic work in the interval since its initial identification.3'4'5 In recent communications we described the development of two different phenol annulations: the first based on the Robinson annulation of D-keto sulfoxides, equation 1, and the second based on the inverse electron demand Diels-Alder reaction of 3-carbomethoxy cc-pyrones with 1 ,l-dimethoxyethylene, ment of a conceptually eqn. 1 1 I J4 : OH equation 2." Herein we would like to disclose our efforts on the developsimple and regiospecific total synthesis of juncusol (1) based on the use eqn. 2 CH3OQCH R = C02CH3 R=H of two such phenol annulations, Scheme I. Implicit in the design of this approach is the ease
with which the substitution pattern of either phenol may be introduced or altered.