EXPERIMENTS DIRECTED TOWARDS THE SYNTHESIS OF ANTHRACYCLINONES .20. TITANIUM(IV)-MEDIATED AND TIN(IV)-MEDIATED CYCLIZATIONS OF ORTHO-ALLYL-SUBSTITUTED HOMOCHIRAL DIOXANS

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 C 9. The exclusive formation of the (7R) stereochemistry results from S(N)2-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 C 9 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 C 10 alcohol (23) as well as the C 9 chloro tetracycles (16) and (17) suggesting that carbocations are involved in some cases.