Exploration of Diels-Alder Reaction of 2-Vinylazoles as 1-Azadienes

含氮六元环（哌啶环）是生物活性化合物的常见部分结构。含氮杂原子的Diels-Alder反应是实现该体系最直接的途径之一。1然而，1-氮杂-1，3-丁二烯（简单的α，β-不饱和亚胺）本身的狄尔斯-阿尔德反应由于其作为二烯的低反应性、副反应和由亚胺部分引起的不稳定性而一直是困难的。我们发现亚苄基氰基甲基-1，3-苯并噻唑和-1，3-苯并恶唑（1）为1-氮杂-1，3-丁二烯。通过构成杂芳环以稳定的亚胺部分为特征的二烯（1）与缺电子亲二烯体和富电子亲二烯体反应。发现分子中含有双烯体系和亲双烯基团的底物能顺利地引发立体选择性的分子内Diels-Alder反应，通过外过渡态生成多环化合物。（E）-3-（1，3-苯并噻唑-2-基）-3-氰基丙烯酸乙酯（2）作为1-氮杂-1，3-丁二烯（2），在二烯-4-位上带有吸电子酯基，在极其温和的条件下与富电子亲二烯体反应，得到相应的环加成物，具有区域选择性和内选择性。用给电子烯丙基醇处理2会导致串联酯交换和分子内环加成，从而在一步中得到顺式稠合多环体系。

Nitrogen containing a six-membered ring system (piperidine ring) is a common partial structure of biologically active compounds. One of the most direct approaches to the system is the nitorogen containing hetero Diels-Alder reaction. 1 However, Diels-Alder reaction of 1-aza-1, 3-butadienes, simple alpha, beta-unsaturated imines, themselves have been difficult due to their low reactivities as dienes, side reactions and instabilities arising from the imine moieties. We found benzylidenecyanomethyl-1, 3-benzothiazoles and -1, 3-benzoxazoles (1) as 1-aza-1, 3-butadienes. The dienes (1) featuring the stabilized imine moieties by constituting heteroaromatic rings, react with both electron-deficient and electron-rich dienophiles. It was found that substrates having the diene systems and dienophiles moiety in the molecules smoothly caused stereoselective intramolecular Diels-Alder reaction to give polycyclic compounds via exo-transition state. Ethyl (E)-3-(1, 3-benzothiazol-2-yl)-3-cyanopropenoate (2) as 1-aza-1, 3-butadiene (2), bearing electronwithdrawing ester group at diene -4-position, reacts with electron -rich dienophiles under extremely mild conditions to give corresponding cycloadducts with regio-and endo-selectivities. Treatment of 2 with electron-donating allyl alcohols causes tandem transesterification and intramolecular cycloaddition to afford cis-fused polycyclic systems in a single step.