Design of a Chiral Dinucleating System Utilizing Tartaric Acid Ester as a Chiral Auxiliary and Its Application to the Synthesis of Optically Active Compounds

为了开发新的生物活性药物和农用化学品，迫切需要开发一种实用高效的手性分子构建方法。在本研究中，利用酒石酸酯设计了一种具有两个金属中心的新型手性体系；也就是说，如果两个反应物结合到酒石酸酯衍生的双氧体的两个不同的金属中心上，实际上可能形成刚性的5/5-稠合双环双核结构，它们可能是理想的取向和/或被金属活化，随后的反应可能以不对称选择性的方式进行，以获得相应的光学活性产物。通过使用(R，R)-酒石酸二异丙酯作为手性辅助，实现了丁腈氧化物与(E)-4-羟基-2-丁烯酸乙酯的不对称1，3-偶极环加成反应以二乙基锌和碘乙酸乙酸酯为原料，原位合成的Reformsky试剂与3，4-二氢异喹啉N-氧化物中的碳-氮双键发生不对称加成反应，对映体选择性高达86%ee。此外，还实现了由醛和2-氨基苯酚制备的亚胺与Reformsky试剂的不对称加成反应，得到β-氨基酸衍生物。为了实现可重复性的高立体选择性，添加少量的水是至关重要的。

It is strongly required to develop a practical and efficient method for the construction of chiral molecules to explore new biologically active medicines and agricultural chemicals. In this research, a new and novel chiral system possessing two metal centers utilizing tartaric acid esters was designed ; that is, if two reactants are bound to two different metal centers of the dialkoxide derived from tartaric acid ester, which might actually form the rigid 5/5-fused bicyclic dinucleating structure, they might be ideally oriented and/or activated by the metals and the following reaction might proceed in an enantioselective manner to afford the corresponding optically active products.The asymmetric 1,3-dipolar cycloaddition of nitrile oxides to ethyl (E)-4-hydroxy-2-butenoate was achieved by the use of diisopropyl (R,R)-tartrate as a chiral auxiliary to afford the corresponding 4,5-trans-2-isoxazolines, which were transformed to the corresponding 4,5-cis-2-isoxazolines by the treatment with a base through isomerization and lactonization.The asymmetric addition of the Reformatsky-type reagent, prepared in situ from diethylzinc and iodoacetic acid ester, to a carbon-nitrogen double bond in 3,4-dihydroisoquinoline N-oxides was achieved with enantioselectivity up to 86% ee. Furthermore, the asymmetric addition of the Reformatsky-type reagent to imines prepared from aldehydes and 2-aminophenol was also achieved to give β-amino acid derivatives. In order to realize reproducible higher stereoselection, the addition of a small amount of water was crucial.