Enantioselective Total Synthesis of Cerorubenic Acid-III via Type II [5+2] Cycloaddition Reaction

The first enantioselective total synthesis of cerorubenic acid-III is described in detail. Different strategies and attempts, based on a type II [5+2] cycloaddition reaction, leading to the bicyclo[4.4.1] ring system with a strained bridgehead double bond, are depicted. Furthermore, sodium naphthalenide was found to be efficient in the chemoselective reduction of 8-oxabicyclo[3.2.1]octene, with three transformations completed in one operation. An unusual SN1 transannular cyclization reaction was applied to construct the synthetically challenging vinylcyclopropane moiety. This strategy enabled the total synthesis of cerorubenic acid-III in 19 steps.