Copper‐Catalyzed Regioselective [3+3] Annulations of Alkynyl Ketimines with <i>α</i>‐Cyano Ketones: the Synthesis of Polysubstituted 4<i>H</i>‐Pyran Derivatives with a CF<sub>3</sub>‐Containing Quaternary Center
Cheng Sheng, Zheng Ling, Tanveer Ahmad, Fang Xie, Wanbin Zhang
Abstract
Abstract Regioselective [3+3] annulation of alkynyl ketimines with α ‐cyano ketones for the synthesis of polysubstituted 4 H ‐pyran derivatives with a quaternary CF 3 ‐containing center has been realized by using Cu(OAc) 2 as the catalyst. The novel strategy tolerates a wide range of α ‐CF 3 alkynyl ketimines and α ‐cyano ketones with both aryl and alkyl substitutents. A preliminary asymmetric synthesis of chiral product 3 has been attempted by using copper and chiral thiourea as the cocatalyst with excellent yields (86‐99 %) and good enantioselectivities (71–78 % ee ). Furthermore, product 3 aa could be obtained on a gram‐scale reaction with 75 % yield and 99 % ee after recrystallization. Several products were also transformed readily. Control experiments indicate that the reaction involves a process with a base‐catalyzed or chiral thiourea‐catalyzed Mannich‐type reaction followed by a highly regioselective copper‐catalyzed ring‐closing reaction on the alkynyl moiety in a 6 ‐endo ‐ dig fashion.