Studies toward the total synthesis of penostatin F

Abstract

The total synthesis of penostatin F (1) has been a goal in our laboratory for the last 6 years. Our first approach developed by Patrick Ang and Roch Lavigne (Scheme 1) involved a hydroxy-directed Diels-Alder (HDDA) reaction between diene 2 and dienophile 4 through the formation of a magnesium alkoxide 3. The single resulting Diels-Alder adduct 5 is then poised to undergo a Claisen rearrangement upon heating, to rapidly afford the bicyclo[5.3.1]undecenone core of penostatin F. Unfortunately, numerous attempts to employ this strategy to complete the synthesis have failed.* This thesis discusses a new approach towards the total synthesis of penostatin F. The key step involves a 6pi electrocyclization of a triene precursor followed by a Claisen rearrangement, as depicted below. Following a successful key step model study, the syntheses of a functionalized alkoxydienyl boronic ester and an enol triflate dihydropyran as coupling partners are described. Issues surrounding the electrocyclization are discussed and possible solutions are presented.* *Please refer to dissertation for diagrams.