Diastereoselective Corey–Chaykovsky 9‑Epoxymethylation of <i>Cinchona</i> Alkaloids: Access to Chiral Scaffolds with Diverse Functionalities

Reaction of dimethylsulfonium methylide with <i>Cinchona</i> alkaloid ketones proceeds with complete diastereoselectivity to give epoxides of 8,9-<i>like</i> configuration. The reaction of dimethylsulfoxonium methylide gives different isomers, albeit with lower (4:1) selectivity. α-Epimerization of the alkaloid ketones resulted in formation of two separable diasteromeric products. The configurations of the epoxides were elucidated on the basis of NMR data combined with DFT calculations. Models explaining observed selectivity are discussed. The epoxides were efficiently transformed to a number of derivatives through selective S_N2-type ring-opening reactions with various nucleophiles, often without the need of additional purification steps