Synthesis of (−)‐Hebelophyllene E: An Entry to Geminal Dimethyl‐Cyclobutanes by [2+2] Cycloaddition of Alkenes and Allenoates. Issue 17 (24th March 2018)

• Record Type: Journal Article
• Authors: Wahl, Johannes M.; Conner, Michael L.; Brown, M. Kevin
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 17(2018)
• Page Start: 4647
• Page End: 4651
• Publication Date: 2018-03-24
• Subjects: cycloaddition -- enantioselectivity -- natural products -- small ring systems -- total synthesis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201801110
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The first synthesis of hebelophyllene E is presented, along with assignment of its previously unknown relative configuration through synthesis of epi‐ent ‐hebelophyllene E. Development of a catalytic enantioselective [2+2] cycloaddition of alkenes and allenoates provides access to the required chiral geminal dimethylcyclobutanes. Key to its success is the identification of a novel oxazaborolidine catalyst which promotes the cycloaddition in high enantioselectivities with good functional‐group tolerance (9 examples, up to 97:3 e.r.). Thus, a late‐stage cycloaddition using a fully functionalized alkene, followed by a diastereoselective reduction allows a concise entry to this class of natural products. Abstract : First design, then assign : The first synthesis of hebelophyllene E is presented, along with assignment of its previously unknown relative configuration through the synthesis of epi‐ent ‐hebelophyllene E. Development of a catalytic enantioselective [2+2] cycloaddition of alkenes and allenoates, followed by diastereoselective conjugate reduction provides access to the required chiral geminal dimethylcyclobutane core.