[2 + 2 + 1]反应合成2,3,5-三取代噻吩衍生物

噻吩骨架存在于替诺立定、西他生坦、莫他匹酮等生物碱中，可用作抗炎药、降压药、PDE3抑制剂. 对该骨架的修饰，一直是有机合成的热点. 在碱促进下，1,4-二羰衍生物和硫氰基芳酮经2 + 2 + 1]反应，构建了噻吩骨架，同时实现了C-2位和C-5位的双芳酰基化、C-3位的芳基化. 分别从红外、核磁、质谱和单晶不同角度证实了产物的结构. 该反应机制涉及3 + 2]环加成、原位开环、互变异构、S_N2反应等过程. 

The [2 + 2 + 1] synthesis of 2,3,5-trisubstituted thiophenes

Thiophene skeleton is present in alkaloids tinoridine, sitaxentan and motapizone, used as anti-inflammatory drugs, anti-hypertensive drugs, and PDE3 inhibitors. Modifications of this skeleton are highly desired. Under the promotion of alkali, 1,4-dicarbonyls and thiocyanato aryl ketone could undergo 2 + 2 + 1] reaction to construct thiophene skeleton. Simultaneously, bisaroylation at C-2 and C-5 positions and arylation at C-3 position were realized. Infrared, nuclear magnetic, mass spectrometry and single crystal all confirmed structure of the product. The reaction should involve 3 + 2] cycloaddition, in situ ring opening, tautomerization, S_N2 reaction and other processes.