The utility of furan-, pyrrole-, and thiophene-based 2-silyloxy dienes as demonstrated by modular synthesis of annonaceous acetogenin core units and their pyrrolidine and thiolane analogues

We report a modular strategy for obtaining the care units of annonaceous ac etogenins and their nitrogen and sulfur analogues, which generates great st ructural diversity. This synthesis is based an the application of a reitera tive vinylogous addition protocol involving a unique triad of silyloxy dien e modules, 2-[(tert-butyldimethylsilyl)oxy]furan (TBSOF), N-(tert-butoxycar bonyl)-2-[(tert-butyldimethylsilyl silyl)oxy]pyrrole (TBSOP), and 2-[(tert- butyldimethylsilyl)oxy]thiophene (TBSOT) and suitable heteroatom-stabilized carbenium ions. By combining TBSOF, TBSOP, and TBSOT nucleophilic synthons with certain tetrahydrofuran, pyrrolidine, and thiolane accepters, the con struction of varied, adjacently linked oligo-heterocyclic motifs related to the core segments of the annonaceous acetogenins is assured. At first, the reliability of the pivotal coupling maneuver was certified, by assembling a collection of 18 model constructs, covering all oxygen, nitrogen, and sul fur heteroatom combinations (i.e., compounds 7-9, 13-15, and 19-21). This u niformed protocol was then suited to forge advanced bis-tetrahydrofuran, bi s-pyrrolidine, and bis-thiolane scaffolds encompassing the heterocyclic cor e portion of various binuclear annonaceous acetogenins and relatives. The u tility of this synthesis was demonstrated by the preparation of a repertoir e of eight isomeriebis-tetrahydrofuran units, 41-48, two bis-pyrrolidine un its, 62 and 63, and four bis-thiolane units, 78-81.