Development of Unique Synthetic Reactions of Ethenetricarboxylate Derivatives using Lewis Acid

1)含氮和氧的五元杂环，如吡咯烷，包括脯氨酸和相关的氨基酸，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和它们的生物活性。本工作发展了一种新的锌和铟促进的共轭加成-环化反应，得到含氮和含氧的五元杂环化合物。在InBr_3-Et_3N（0.2equiv.）存在下，三羧酸乙烯酯和丙二酸亚甲基酯1与炔丙胺（1 equiv.）在80 ℃下反应4 h，得到亚甲基吡咯烷，产率为73-75%。1与炔丙醇在ZnBr_2或InBr_3存在下于80 ℃反应，得到四氢呋喃，产率66-89%。还检查了取代的炔丙醇。1和γ-硅取代炔丙醇与ZnBr_2在80-110 ℃反应，立体选择性地生成（Z）-硅取代产物。1和γ-酯基的反应 ...更多信息 用ZnBr_2取代炔丙醇2，立体选择性地得到（Z）-酯取代产物。另一方面，1和2与SnCl_4在室温下的反应，在室温下的反应温度为20 ℃。只得到E-取代的四氢呋喃。2）Friedel-Crafts反应是生成新的C-C键的重要反应。最近，亚烷基丙二酸酯的催化不对称Friedel-Crafts反应被报道。然而，亚烷基丙二酸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，研究了反应性乙烯三羧酸酯和酰基取代的亚甲基丙二酸酯1的催化不对称Friedel-Crafts反应. 1与吲哚在催化量的手性双恶唑啉铜（II）配合物（10%）存在下于THF中室温反应，得到了高产率的烷基化产物，其ee值高达95%.1-Cu（II）-配体配合物的对映选择性可以用吲哚靠近低阻侧的二级轨道相互作用来解释.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