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

Abstract

Titanium(IV) chloride mediated cyclization of the ortho-methoxylated 1,3-dioxan (5) gives a high yield of a mixture (10:1) of the (7R)- tetracycles (18) and (19) which are epimeric at C9. The exclusive formation of the (7R) stereochemistry results from SN2-like attack of the olefin on a chelate involving the o- methoxy group and the dioxan ring. Ion pairing plays a major role in determining the C9 stereochemistry with internal delivery of a chloride ion giving the major product (18). The presence of a hydroxy group meta to the 1,3-dioxan as in (4) does not affect the stereoselectivity , but cyclization affords the C10 alcohol (23) as well as the C9 chloro tetracycles (16) and (17) suggesting that carbocations are involved in some cases.