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(sp(2)) 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.

Automated summary

A new method for constructing propionate-derived trisubstituted alkene motifs with stereoselectivity has been reported. The method involves the ruthenium(II)-catalyzed double-bond transposition of 1-substituted 1,1-di(pinacolatoboryl)-alk-3-enes to generate E isomers of anti-homoallylic alcohols, while using a dimeric palladium(I) complex leads to the formation of Z isomers. The motifs can be successfully applied to the syntheses of specific compounds.