Diastereoselective oxocarbenium ion-mediated reactions directed by the alpha-(trimethylsilyl)benzyl auxiliary

A novel chiral auxiliary for oxocarbenium ion-mediated reactions has been developed and was found to efficiently direct both the intermolecular and intramolecular additions of nucleophiles. The alpha-(trimethylsilyl)benzyl auxiliary was designed based on Linderman's studies of diastereoselective nucleophilic additions to alpha-silyl oxocarbenium ions, in which diastereoselectivity was thought to be controlled by a stereoelectronic effect analogous to the beta-silyl effect. Herein will be presented an expedient synthesis of optically pure alpha-(trimethylsilyl)benzyl alcohol, using a key enantioselective hydrogenation of benzoyltrimethylsilane with Noyori's chiral Ruthenium catalyst. The alcohol was found to efficiently direct in situ allylations of various aldehydes, as well as additions of various nucleophiles to auxiliary-modified alpha-acetoxy ethers. The auxiliary-protected products could be converted to optically active benzyl ethers or alcohols.; The alpha-(trimethylsilyl)benzyl auxiliary was an efficient chiral initiator for a simple polyene cyclization, generating a decalin product of high enantiopurity. Application of the polyene cyclization methodology was initiated in studies toward the synthesis of diterpenoid natural product 19(4→3) abeo-8alpha,13(S)-epoxylabda-4(18),14-diene 5-1. A convergent synthesis of various auxiliary-modified cyclization precursors will be described, as well as preliminary tricyclization results.