Organic Chemistry

Global Diastereoconvergence in the Ireland–Claisen Rearrangement of Isomeric Enolates: Synthesis of Tetrasubstituted -Amino Acids



A dual experimental/theoretical investigation of the Ireland–Claisen rearrangement of tetrasubstituted a-phthalimido ester enolates to afford a-tetrasubstituted, b-trisubstituted a-amino acids (generally >20:1 dr) is described. For trans allylic olefins, the Z and E-enol ethers proceed through chair and boat transition states, respectively. For cis allylic olefins, the trend is reversed. As a result, the diastereochemical outcome of the reaction is preserved regardless of the geometry of the enolate or the accompanying allylic olefin. We term this unique convergence of all possible olefin isomers as global diastereoconvergence. This reaction manifold circumvents limitations in present-day technologies for the stereoselective enolization of a,a-disubstituted allyl esters. Density func- tional theory paired with state-of-the-art local coupled-cluster theory (DLPNO-CCSD(T)) was employed for the accurate determina- tion of quantum mechanical energies.


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Supplementary material

Thumbnail image of Ireland-Claisen Supporting Information.pdf
Ireland-Claisen Supporting Information
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Thumbnail image of IrelandClaisenData.xlsx