Experiments Directed Towards the Synthesis of Anthracyclinones. XXXIII. Hetero-Diels-Alder Reactions Using Togni's Catalyst

Abstract

(+)-Bis[3-(heptafluorobutyryl)camphorato]oxovanadium(IV) [(+)-VO(hfc)₂] (2) is an effective catalyst for the hetero-Diels-Alder reaction of a variety of anthraquinone aldehydes and silyloxy dienes giving high yields of cycloadducts. The reactions all proceed with strict endo topology giving rise to cis products; this indicates that they follow a similar mechanistic pathway to that proposed by Danishefsky for reactions catalysed by the europium complexes Eu(fod)₃ and Eu(hfc)₃. Reactions employing the dimethoxy aldehydes (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 the nature of a substituent at C1 can have a significant effect. Enantioselectivity is generally higher for reactions at low temperature and when toluene rather than dichloromethane is used as solvent. The cycloadduct (24) has been elaborated to the anthracene C-glycoside (28) of known configuration, thereby 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 ¹H n.m.r. spectrum of the ketone (17), a derivative of (24), in the presence of the solvating 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 silyloxy dienes with terminal silyloxy or methyl substituents for such syntheses.