Stereo- and Enantioselective Synthesis of Propionate-Derived Trisubstituted Alkene Motifs

We report a new method for constructing propionate-derived trisubstituted alkene motifs in a stereoselective manner. 1-Substituted 1,1-di(pinacolatoboryl)-(E)-alk-2-enes are generated in situ from 1-substituted 1,1-di(pinacolatoboryl)alk-3-enes through ruthenium(II)-catalyzed double-bond transposition. These species undergo a chiral phosphoric acid catalyzed allylation reaction of aldehydes to produce the E isomers of anti-homoallylic alcohols. On the other hand, the corresponding Z isomers of anti-homoallylic alcohols are obtained when a dimeric palladium(I) complex is employed as the catalyst for this double-bond transposition. Thus, both E and Z isomers can be synthesized from the same starting materials. A B−C(sp²) bond remaining with the allylation product undergoes the Suzuki–Miyaura cross-coupling reaction to furnish a propionate-derived trisubstituted alkene motif in a stereo-defined form. The present method to construct the motifs with (E)- and (Z)-alkenes are successfully applied to the syntheses of (+)-isotrichostatic acid, (−)-isotrichostatin RK, and (+)-trichostatic acid, respectively.