Stereo-controlled Synthesis of Vicinal Tertiary Carbinols: Application in the Synthesis of Zaragozic Acid, Pactamycin and Ryanodol Core Structures.

Abstract

Here we report a novel and flexible approach for the stereo-controlled synthesis of vicinal tertiary carbinols. The developed strategy featured a highly diastereoselective singlet-oxygen (O21) [4+2] cycloaddition of rationally designed cyclohexadienones (derived from oxidative dearomatization of the corresponding carboxylic-acid appended phenol precursors), followed by programmed "O-O" and "C-C" bond cleavage. In doing so, a highly functionalized and versatile intermediate was identified and prepared in synthetically useful quantity as a plausible precursor to access a variety of designed and naturally occurring vicinal tertiary carbinol containing compounds. Most notably, the developed strategy was successfully applied in the stereo-controlled synthesis of advanced core structures of zaragozic acid, pactamycin and ryanodol.