Racemic hemiacetals as oxygen-centered pronucleophiles triggering cascade 1,4-addition/Michael reaction through dynamic kinetic resolution under iminium catalysis. Development and mechanistic insights† †Electronic supplementary information (ESI) available: Detailed experimental procedures and characterization of all new compounds, including copies of NMR spectra and HPLC chromatograms traces, computational details and Cartesian coordinates of all stationary points. CCDC 1525188 (4l), 1525189 (6a

• Published in: Chemical science (Cambridge) Vol. 8; no. 4; pp. 2904 - 2913
• Main Authors: Orue, Ane, Uria, Uxue, Roca-López, David, Delso, Ignacio, Reyes, Efraím, Carrillo, Luisa, Merino, Pedro, Vicario, Jose L.
• Format: Journal Article
• Language: English
• Published: Royal Society of Chemistry 30.01.2017
• Subjects: Chemistry
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c7sc00009j

Racemic 2-hydroxydihydropyran-5-ones react as unconventional O -pronucleophiles in a conjugate addition/Michael reaction cascade process under DKR, leading to the formation of a single stereoisomer out of 16 possible ones. 2-Hydroxydihydropyran-5-ones behave as excellent polyfunctional reagents able to react with enals through oxa-Michael/Michael process cascade under the combination of iminium and enamine catalysis. These racemic hemiacetalic compounds are used as unconventional O -pronucleophiles in the initial oxa-Michael reaction, also leading to the formation of a single stereoisomer under a dynamic kinetic resolution (DKR) process. Importantly, by using β-aryl or β-alkyl substituted α,β-unsaturated substrates as initial Michael acceptors either kinetically or thermodynamically controlled diastereoisomers were formed with high stereoselection through the careful selection of the reaction conditions. Finally, a complete experimental and computational study confirmed the initially proposed DKR process during the catalytic oxa-Michael/Michael cascade reaction and also explained the kinetic/thermodynamic pathway operating in each case.