Kinetic and thermodynamic stereocontrol in the atroposelective formation of sulfoxides by oxidation of 2-sulfanyl-1-naphthamides

Atropisomeric aromatic amides bearing 2-sulfanyl groups are oxidised by m-CPBA to the corresponding sulfoxides apparently with very high diastereoselectivity. NMR studies and oxidations of chiral benzamides however indicate that the kinetic selectivity of the oxidation is in fact relatively poor, and that the final diastereoisomeric ratio (typically >99:1) is under thermodynamic control, with relatively unhindered Ar-CO rotation readily converting the less stable to the more stable product diastereoisomer. Molecular mechanics indicates that the thermodynamic diastereoselectivity results principally from electrostatic repulsion between the C=O and S-O dipoles. © The Royal Society of Chemistry 2005.