Sheng Cheng, Ling Zheng, Ahmad Tanveer, Xie Fang, Zhang Wanbin
Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Frontier Science Center for Transformative Molecules, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, China.
College of Chemistry, Zhengzhou University, Zhengzhou, 450052, China.
Chemistry. 2022 Apr 22;28(23):e202200128. doi: 10.1002/chem.202200128. Epub 2022 Mar 18.
Regioselective [3+3] annulation of alkynyl ketimines with α-cyano ketones for the synthesis of polysubstituted 4H-pyran derivatives with a quaternary CF -containing center has been realized by using Cu(OAc) as the catalyst. The novel strategy tolerates a wide range of α-CF 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.
以Cu(OAc)为催化剂，实现了炔基酮亚胺与α-氰基酮的区域选择性[3+3]环化反应，用于合成具有含季碳CF中心的多取代4H-吡喃衍生物。该新策略适用于多种带有芳基和烷基取代基的α-CF炔基酮亚胺和α-氰基酮。通过使用铜和手性硫脲作为共催化剂，对手性产物3进行了初步的不对称合成，产率优异（86-99%），对映选择性良好（71-78% ee）。此外，产物3 aa在重结晶后可通过克级规模反应获得，产率为75%，ee值为99%。几种产物也易于转化。对照实验表明，该反应涉及一个过程，即碱催化或手性硫脲催化的曼尼希型反应，随后是高度区域选择性的铜催化的炔基部分以6-内型方式进行的闭环反应。
