L‐Proline/CoCl2‐Catalyzed Highly Diastereo‐ and Enantioselective Direct Aldol Reactions

The CoCl2/l-proline (1:2) system was found to be an excellent catalyst for direct aldol reactions. Ex- cellent yields (up to 93 %) and a signif- icant improvement in diastereoselectiv- ity (anti/syn up to 45:1) as well as enantioselectivity (up to more than 99 % ee) compared with using proline as the sole catalyst were observed. This catalyst system was successfully applied to both cyclic and acyclic ketones in combination with aromatic and aliphat- ic aldehydes. In situ chelation of CoCl2 and proline (1:2) is proposed to pro- mote the reaction through a six-mem- bered Zimmermann-Traxler type tran- sition state involving the positioning of proline-enamine and the aldehyde through chelation to Co II .