Modular Enantioselective Total Syntheses of the -7,9-Dihydroxy- and 9-Hydroxy-7-Keto-8,4'-Oxyneolignans.

A modular, enantioselective approach to access the bioactive 7,9-dihydroxy- and 9-hydroxy-7-keto-8,4'-oxyneolignans is disclosed, which employs stereoselective Mitsunobu reactions of enantiopure 2-aryl-1,3-dioxan-5-ols and functionalized phenols. The enantiopure dioxanols are prepared through Sharpless asymmetric dihydroxylation of protected coniferyl or sinapyl alcohols and subsequent benzylidene acetal formation. Through a mix-and-match coupling approach, six of the eight possible -7,9-dihydroxy-8,4'-oxyneolignan enantiomeric natural products (bearing a C-1' hydroxypropyl chain) were generated following sequential deprotection. Subsequent benzylic oxidation afforded the 7-keto-derivatives, resulting in enantioselective syntheses of each enantiomer of the natural products asprenol B and icariol A.