Experiments Directed Towards the Synthesis of Anthracyclinones. XVI. Tin(IV)- and Titanium(IV)-Mediated Cyclizations of ortho-Allyl-Substituted Homochiral Hydroxyanthraquinone Dioxolans

Abstract

Tin(IV) chloride and titanium(IV) chloride mediated cyclizations of the ortho-allyl-substituted homochiral hydroxyanthraquinone acetals (7)-(10), prepared by optimized redictive Claisen rearrangements, have afforded monochloro and dichloro tetracyclic products, the tereochemistry of which has been assigned by using n.m.r. techniques. An S_n2-like process in which the dioxolan ring is maintained as an ion pair intermediate is favoured when either tin(IV) chloride or titanium(IV) chloride is used at -78º. Thereafter the direction of addition of chloride at C9 is largely governed by the orientation of this ion pair. An alternative path which probably involves a free oxocarbenium ion predominates at higher temperatures. An adjacent methoxy group on the anthraquinone lowers the stereoselectivity at both C7 and C9, possibly by bidentate coordination of the Lewis acid involving the quinone carbonyl, the methoxy oxygen and the acetal oxygens.