Experiments directed towards the synthesis of anthracyclinones .28. Titanium(IV)- and tin(IV)-mediated cyclizations of ortho-methallyl-substituted homochiral dioxans

Metal chloride cyclizations of the 4-demethoxy anthraquinonyl 1',3'-dioxan (6) are highly diastereoselective, giving 9-chloro-9-methylanthracyclinones in high yield. The selectivity is inversely proportional to the strength of the Lewis acid, with the mild Lewis acid tin(IV) chloride/dimethylformamide affording an 82% yield of the diastereomer (21). The predominant products have a (7S) configuration and a trans relationship between the C7 side chain and the 9-chloro substituent. Cyclization of the analogous dimethoxy 1',3'-dioxan (4) with tin(IV) chloride/dimethylformamide is considerably less selective, but the major product also has a (7S)-trans stereochemistry. Titanium(IV) chloride effects stereorandom cyclization of (4).