Origin of High Diastereoselectivity in Reactions of Seven‐Membered‐Ring Enolates. Issue 14 (15th February 2022)

• Record Type: Journal Article
• Authors: Lavinda, Olga; Witt, Collin H.; Woerpel, K. A.
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 14(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-15
• Subjects: Conformational Analysis -- Diastereoselectivity -- Enolates -- Seven-Membered-Rings -- Torsional Strain; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202114183
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Unlike many reactions of their six‐membered‐ring counterparts, the reactions of chiral seven‐membered‐ring enolates are highly diastereoselective. Diastereoselectivity was observed for a range of substrates, including lactam, lactone, and cyclic ketone derivatives. The stereoselectivity arises from torsional and steric interactions that develop when electrophiles approach the diastereotopic π‐faces of the enolates, which are distinguished by subtle differences in the orientation of nearby atoms of the ring. Abstract : The diastereoselective reactions of chiral seven‐membered‐ring enolates have been systematically investigated. Diastereoselectivity was found to be general for ϵ‐lactams, ϵ‐lactones, and cycloheptanones with various substituent patterns. Computational investigations provided insight into the origin of the diastereoselectivity. A model for predicting the stereochemistry of seven‐membered‐ring enolate alkylations is proposed.