Innovation of Asymmetric Cycloaddition Reactions Based on Highly Efficient Stereocontrol in Multinucleating Chiral Reaction Field

为了发展一种实用的手性分子构建方法，我们设计了一种以酒石酸酯为手性配体的新型多金属中心手性体系，N-二异丙基酰胺与烯丙醇反应，得到二或三取代异恶唑烷，对映选择性高达99%以上ee.将本发明的不对称1，3-偶极环加成应用于（2S，4 R）-4-羟基鸟氨酸衍生物，利用酒石酸酯作为手性助剂，实现了亚硝基化合物与二烯醇的区域和对映选择性异Diels-Alder反应，得到了完全区域选择性的环化加成物，其对映选择性高达84% ee.利用（R，R）-酒石酸二异丙酯作为手性助剂，实现了苯并环丁烯醇原位生成的邻醌二甲烷与富马酸酯的不对称Diels-Alder反应，得到了相应的光学活性1，2-顺式取代的1-羟基四氢萘衍生物，对映选择性高达83%ee.炔基锌试剂的不对称加成，以二烷基锌和1-炔为原料，利用（R，R）-酒石酸二叔丁酯为手性助剂，原位合成了相应的光学活性的（R）-α-取代炔丙基N-羟胺。通过添加产物样N-羟胺，观察到前所未有的对映选择性增强，得到高达95%ee的N-羟胺。

In order to develop a practical method for the construction of chiral molecules, we have designed a novel chiral system possessing multi-metal centers utilizing tartaric acid ester as a chiral auxiliary.A catalytic asymmetric 1,3-dipolar cycloaddition of nitrones possessing the N,N-diisopropylamide moiety to allylic alcohols was achieved to afford di- or trisubstituted isoxazolidines with excellent enantioselectivity of up to over 99% ee. The present asymmetric 1,3-dipolar cycloaddition was applied to the synthesis for the (2S,4R)-4-hydroxyornithine derivative.The regio- and enantioselective hetero Diels-Alder reaction of nitroso compound with dienol has been realized utilizing a catalytic amount of tartaric acid ester as a chiral auxiliary and the corresponding cycloadduct was obtained in complete regioselectivity with excellent enantioselectivity up to 84% ee.The asymmetric Diels-Alder reaction of o-quinodimethanes, generated from benzocyclobutenols in situ, with fumaric acid esters was achieved by utilizing diisopropyl (R,R)-tartrate as a chiral auxiliary to afford the corresponding optically active 1,2-cis-substituted 1-hydroxy tetrahydronaphthalene derivatives with enantioselectivity up to 83% ee.The asymmetric addition of alkynylzinc reagents, prepared in situ from dialkylzinc and 1-alkynes, to nitrones was achieved by utilizing di(t-butyl) (R,R)-tartrate as a chiral auxiliary to afford the corresponding optically active (R)-α-substituted propargylic N-hydroxylamines. By the addition of product-like N-hydroxylamine, unprecedented enhancement of enantioselectivity was observed to afford the N-hydroxylamines up to 95% ee.