Conjugate addition approach for natural product synthesis inspired by gibberellin and solanoeclepin A targets

Trimethylzincate is known to react through conjugate addition to alpha,beta-unsaturated ketones, but adds much faster to alpha,beta-unsaturated esters at low temperatures. Since the intermediate zinc enolate behaves differently from that of dimethylcuprate, it offers scope for application in a partial synthesis of gibberellin A(3). A second example involving vinylsulfones having an oxygen atom on the gamma-carbon strongly directs incoming nucleophiles in conjugate addition mode. Heteroatom-directed conjugate addition (HADCA) provides very reactive carbanion intermediates leading to cyclobutane ring formation, necessary for synthesis of solanoeclepin A. An alternative reaction for the four-membered carbocyclic ring closure was explored to make a bond formation between the propargylic cation of Nicholas type and allyltrimethylsilane nucleophile of Hosomi-Sakurai type. This method allowed a formation of tricyclo[5.2.1.0(1,6)]decene framework.