Experiments directed towards the synthesis of anthracyclinones. XXXIII - Hetero-Diels-Alder reactions using Togni's catalyst

(+)-Bis[3-(heptafluorobutyryl)camphorato]oxovanadium(IV) [(+)-VO(hfc)(2)] ( 2) is an effective catalyst for the hetero-Diels-Alder reaction of a variet y of anthraquinone aldehydes and silyloxy dienes giving high yields of cycl oadducts. The reactions all proceed with strict endo topology giving rise t o cis products; this indicates that they follow a similar mechanistic pathw ay to that proposed by Danishefsky for reactions catalysed by the europium complexes Eu(fod)(3) and Eu(hfc)(3). Reactions employing the dimethoxy alde hydes (3) and (4) and the phenolic aldehydes (5) and (6) proceed with only modest degrees of enantioselection. Reaction with the benzyloxy aldehyde (7 ) proceeds with significantly reduced enantioselectivity indicating that th e nature of a substituent at C1 can have a significant erect. Enantioselect ivity is generally higher for reactions at low temperature and when toluene rather than dichloromethane is used as solvent. The cycloadduct (24) has b een elaborated to the anthracene C-glycoside (28) of known configuration, t hereby establishing that the hetero-Diels-Alder reaction favours formation of the 2'R,6'R enantiomer of (24). This enantiofacial selectivity has been correlated with the sense of anisochrony observed in the H-1 n.m.r. spectru m of the ketone (17), a derivative of (24), in the presence of the solvatin g agent (S)-(+)-trifluoroanthrylethanol [(S)-(+)-TFAE]. The enone (21) has been elaborated to the anthraquinone olivose C-glycoside (33), a synthesis demonstrating the utility of hetero-Diels-Alder reactions involving silylox y dienes with terminal silyloxy or methyl substituents for such syntheses.