Enantioselective Intramolecular [2+2]-Photocycloaddition Reactions of 4-Substituted Quinolones Catalyzed by a Chiral Sensitizer with a Hydrogen-Bonding Motif
Enantioselective Intramolecular [2+2]-Photocycloaddition Reactions of 4-Substituted Quinolones Catalyzed by a Chiral Sensitizer with a Hydrogen-Bonding Motif
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DOI：
10.1021/ja207480q
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发表时间：
2011-10-19
影响因子：
15
通讯作者：
Bach, Thorsten
中科院分区：
文献类型：
--
作者：
Mueller, Christiane;Bauer, Andreas;Bach, Thorsten
合成了六种 2-喹诺酮，其带有通过三元或四元链连接至喹诺酮碳原子 C4 的末端烯烃，并进行分子内 [2 + 2]-光环加成。该反应以高产率 (78-99%) 产生了各自的产物，并且具有良好的区域选择性，有利于直链异构体。如果在手性氢键模板（2.5当量）存在下在低温下以甲苯为溶剂进行，则反应以对映选择性进行（83-94% ee）。当使用带有附加敏化单元（二苯甲酮或呫吨酮）的手性氢键模板时，实现了有机催化反应。与相应的二苯甲酮相比，基于呫吨酮的有机催化剂被证明是优越的。仔细检查发现，4-(戊-4-烯氧基)喹诺酮生成六元环并与环丁烷稠合的反应，其对映选择性(在 30 mol % 催化剂下高达 41% ee) 比 4-(丁-3-烯氧基)喹诺酮生成五元环的反应 (90% ee 与 5 mol% 和 94% ee 与20 摩尔％催化剂）。光物理数据（发射光谱、激光闪光光解实验）证明后一种光环加成速度明显更快，支持了光环加成之前底物从催化剂上解离导致对映选择性降低的观点。在优化条件下，使用10 mol%的呫吨酮基有机催化剂，在-25℃下以三氟甲苯为溶剂，其他四种底物中的三种得到了具有高对映选择性（72-87% ee）的分子内[2 + 2]-光环加成产物。在所有催化反应中，基于转化率的产率中等至良好（40-93%）。
Six 2-quinolones, which bear a terminal alkene linked by a three- or four-membered tether to carbon atom C4 of the quinolone, were synthesized and subjected to an intramolecular [2 + 2]-photocycloaddition. The reaction delivered the respective products in high yields (78-99%) and with good regioselectivity in favor of the straight isomer. If conducted in the presence of a chiral hydrogen-bonding template (2.5 equiv) at low temperature in toluene as the solvent, the reaction proceeded enantioselectively (83-94% ee). An organocatalytic reaction was achieved when employing a chiral hydrogen-bonding template with an attached sensitizing unit (benzophenone or xanthone). The xanthone-based organocatalyst proved to be superior as compared to the respective benzophenone. Closer inspection revealed that the reaction of 4-(pent-4-enyloxy)quinolone leading to a six-membered ring, annelated to the cyclobutane, was less enantioselective (up to 41% ee with 30 mol % catalyst) than the reaction of 4-(but-3-enyloxy)quinolone leading to a five-membered ring (90% ee with 5 mol % and 94% ee with 20 mol % catalyst). Photophysical data (emission spectra, laser flash photolysis experiments) proved that the latter photocycloaddition was significantly faster, supporting the idea that the dissociation of the substrate from the catalyst prior to the photocycloaddition is responsible for the decreased enantioselectivity. Under optimized conditions, employing 10 mol % of the xanthone-based organocatalyst at -25 degrees C in trifluorotoluene as the solvent, three of the other four substrates gave the intramolecular [2 + 2]-photocycloaddition products with high enantioselectivities (72-87% ee). In all catalyzed reactions, the yields based on conversion were moderate to good (40-93%).