Organocatalytic asymmetric synthesis of quinine and quinidine

Quinine and quinidine were synthesized by a highly enantio- and stereoselective approach starting from a proline-catalyzed asymmetric cycloaldolization of benzyl bis(2-formylethyl)carbamate which gave a 70:30 mixture of (3R,4R)-N-Cbz-3-hydroxymethyl-4-hydroxypiperidine (96% ee) and its 4S-epimer (92% ee) in 94% yield after in situ NaBH₄ reduction.