Celebi-Olçüm Nihan, Sanyal Amitav, Aviyente Viktorya
Department of Chemistry, Boğaziçi University, Bebek, Istanbul 34342, Turkey.
J Org Chem. 2009 Mar 20;74(6):2328-36. doi: 10.1021/jo802365v.
Recyclable chiral anthracene templates have emerged as an effective and well-designed approach in preparing complex biologically active molecules such as butenolides, alpha,beta-unsaturated lactams, and related compounds in their enantiomerically pure forms. Highly diastereoselective initial cycloaddition serves as the key element of the total process, as it determines the final stereochemistry of the product. The diastereoselectivity of chiral anthracene templates is explored by using density functional theory (DFT) methods, and the reliability and applicability of the previously proposed models, mostly based on steric arguments, are tested by mechanistic means. The diastereomers A and B are identified according to the stereochemistry around the formed stereocenter on the dienophile attached to C9, as being R or S, respectively. The reactions of (R)-9-(1-methoxyethyl)anthracene and (S)-9-(1-methoxy-2,2,2-trifluoroethyl)anthracene with maleic anhydride both give exclusively diastereomer A via a similar transition state in which the CH(3)/CF(3) group is antiperiplanar to the approaching dienophile. The major product of the reaction between (R)-9-(1-phenylethyl)aminoanthracene and maleic anhydride is diastereomer B. The geometry around nitrogen is close to planar in the transition state (10-25 degrees out of plane), and the nitrogen lone pair is antiperiplanar to the incoming dienophile. Both of the lowest energy diastereomeric transition states giving A and B benefit from the favorable interaction between the carbonyl oxygen and the amine hydrogen; this interaction does not play a substantial role in the selectivity of the reaction as previously proposed. The diastereomeric transition states leading to A and B for the reaction between (R)-9-acyloxyanthracene and maleic anhydride have very similar interactions around the reaction center, leading to a very small energy difference between the diastereomeric transition states. The product distribution ratios for all templates calculated from Boltzmann distributions agree very well with the experimental results.
可回收的手性蒽模板已成为一种有效且设计精良的方法，用于制备对映体纯形式的复杂生物活性分子，如丁烯内酯、α,β-不饱和内酰胺及相关化合物。高度非对映选择性的初始环加成反应是整个过程的关键要素，因为它决定了产物的最终立体化学。通过密度泛函理论（DFT）方法探索了手性蒽模板的非对映选择性，并通过机理手段测试了先前提出的主要基于空间位阻观点的模型的可靠性和适用性。根据连接在C9上的亲双烯体上形成的立体中心周围的立体化学，将非对映异构体A和B分别鉴定为R型或S型。(R)-9-(1-甲氧基乙基)蒽和(S)-9-(1-甲氧基-2,2,2-三氟乙基)蒽与马来酸酐的反应均通过类似的过渡态专一性地生成非对映异构体A，其中CH(3)/CF(3)基团与接近的亲双烯体呈反式共平面。(R)-9-(1-苯乙基)氨基蒽与马来酸酐反应的主要产物是非对映异构体B。在过渡态中，氮周围的几何结构接近平面（偏离平面10 - 25度），氮孤对与进入的亲双烯体呈反式共平面。给出A和B的两个最低能量的非对映异构过渡态都受益于羰基氧与胺氢之间的有利相互作用；这种相互作用并不像先前提出的那样在反应选择性中起重要作用。(R)-9-酰氧基蒽与马来酸酐反应生成A和B的非对映异构过渡态在反应中心周围具有非常相似的相互作用，导致非对映异构过渡态之间的能量差非常小。根据玻尔兹曼分布计算的所有模板的产物分布比与实验结果非常吻合。
