Enantioselective Total Synthesis of Cerorubenic Acid-III via Type II [5+2] Cycloaddition Reaction
Xin Liu1, Junyang Liu1,2, Jianlei Wu1
1Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Shenzhen Grubbs Institute, Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.
Abstract:
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.
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