Robust, Enantioselective Construction of Challenging, Biologically Relevant Tertiary Ether Stereocenters
- 12 May 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Catalysis
- Vol. 11 (10), 6325-6333
- https://doi.org/10.1021/acscatal.1c01095
Abstract
A robust, catalytic enantioselective method to construct challenging, biologically relevant, tertiary ether stereocenters has been developed. The process capitalizes on readily accessible bis(oxazoline) ligands to control the facial selectivity of the addition of copper acetylides to benzopyrylium triflates, reactive species generated in situ. Up to 99%, enantiomeric excesses are achieved with a broad substrate scope. Using density functional theory (DFT) calculations, the origin of the experimentally observed enantiocontrol was attributed to additional noncovalent interactions observed in the transition state, leading to the major enantiomer, such as p-stacking. The resultant substrates have direct applications in the synthesis of naturally occurring bioactive chromanones and tetrahydroxanthones.Funding Information
- National Institute of General Medical Sciences (NIGMS 1R35GM124804-01)
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