Development of Unique Synthetic Reactions of Ethenetricarboxylate Derivatives using Lewis Acid

1)含氮、含氧的五元杂环，如四氢呋喃、四氢呋喃和四氢呋喃，是有机化学中重要的核心结构，因为它们存在于许多天然产物中，具有生物活性。在本工作中，我们开发了一种新的锌和铟促进的共轭加成-环化反应来合成含氮和氧的五元杂环。在InBr3-Et3N(0.2当量)存在下，三元乙酸乙酯和1亚甲基丙二酸甲酯与丙烯酰胺(1当量)的反应。在80℃下反应4 h，亚甲基吡咯烷的产率为73-75%。在溴化锌或溴化铟存在下，1，3-丙叉醇在80℃下反应生成四氢呋喃，产率为66-89%。对取代的炔丙醇也进行了检测。1和γ硅基取代的炔丙醇在80~110℃的温度下与ZnBr2反应生成(Z)硅基取代的产物。1与γ-酯-…的反应更多的丙叉醇2与溴化锌反应生成(Z)-酯取代产物。另一方面，在反应温度下，1和2与SnCl4的反应。独家给出了E-取代的四氢呋喃。因此，发现了2的反应对立体选择性的有趣的Lewis酸依赖性。α-取代炔丙醇的反应也得到了环化产物2)Friedel-Craft反应是形成新的C-C键的重要反应。最近有报道了丙二酸亚烷酯的催化对映体选择性的Friedel-Craft反应。然而，丙二酸亚烷酯中的取代基是有限的。为了探索新的取代基，如羧基和羰基，我们研究了反应性的亚甲基丙二酸甲酯和反应性的亚甲基丙二酸甲酯的催化不对称Friedel-Craft反应。1与吲哚在催化量的手性双恶唑啉铜(II)配合物(10%)的催化下，在室温下反应，得到高产率的烷基化产物，ee可达95%。这种对映体选择性可以用吲哚靠近1-铜(II)配体络合物受阻较小一侧的二级轨道相互作用来解释。较少

1) Nitrogen and oxygen-containing five-membered heterocycles such as pyrrolidines, including proline and related amino acids, and tetrahydrofurans are important core structures in organic chemistry because of their presence in many natural products and their biological activity. In this work, a new zinc and indium-promoted conjugate addition-cyclization reaction to afford nitrogen and oxygen-containing five-membered heterocycles has been developed. Reaction of ethenetricarboxylates and methylenemalonate 1 with propargylamines (1 equiv) in the presence of InBr_3-Et_3N (0.2 equiv.) at 80 ℃ for 4 h afforded methylenepyrrolidines in 73-75% yields. Reaction of 1 with propargyl alcohol in the presence of ZnBr_2 or InBr_3 at 80 ℃ afforded tetrahydrofurans in 66-89% yields. Substituted propargyl alcohols were also examined. Reaction of 1 and γ-silicon-substituted propargyl alcohols with ZnBr_2 at 80-110 ℃ led to (Z)-silicon-substituted products stereoselectively. Reaction of 1 and γ-ester-subs … More tituted propargyl alcohol 2 with ZnBr_2 gave (Z)-ester-substituted products stereoselectively. On the other hand, reaction of 1 and 2 with SnCl_4 at r.t. gave E-substituted tetrahydrofurans exclusively. Thus, interesting Lewis acid-dependency on stereoselectivity for the reaction of 2 was found. Reaction of a-substituted propargyl alcohols also gave cyclized products.2) The Friedel-Crafts reaction is an important reaction for the formation of new C-C bonds. Recently, catalytic enantioselective Friedel-Crafts reaction of alkylidene malonates has been reported. However, the substituents in alkylidene malonates are limited. In order to explore new substituents such as carboxyl and carbonyl groups, catalytic enantioselective Friedel-Crafts reactions of reactive ethenetricarboxylates and acyl-substituted methylenemalonates 1 were investigated. The reaction of 1 with indoles in the presence of catalytic amounts of chiral bisoxazoline cupper(II) complex (10%) in THE at room temperature gave alkylated products in high yields and up to 95% ee. The enantioselectivity can be explained by the secondary orbital interaction on approach of indole to the less hindered side of the 1-Cu(II)-ligand complex. Less