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

为了开发一种实用的手性分子构筑方法，我们以酒石酸酯为手性助剂，设计了一种具有多金属中心的新型手性体系，实现了具有N，N-二异丙酰胺结构的硝酮与烯丙醇的不对称1，3-偶极环加成反应，得到了对映体选择性高达99%ee以上的二或三取代异恶唑烷。将不对称1，3-偶极环加成反应应用于(2S，4R)-4-羟基鸟氨酸衍生物的合成，以酒石酸酯为手性助剂，实现了亚硝基化合物与二烯醇的区域和对映异Diels-Alder反应，得到了相应的环加合物，其对映体选择性最高可达84%E.苯环丁烯原位生成的邻喹基二甲烷与富马酸酯的不对称Diels-Alder反应是通过(R，以酒石酸二(叔丁基)(R，R)-酒石酸酯为手性助剂合成了光学活性的1，2-顺式取代的1-羟基四氢萘衍生物，对映体选择性高达83%E E。以(R，R)-酒石酸二(叔丁基)-酒石酸酯为手性助剂，原位合成了具有光学活性的(R)-α取代丙叉N-羟胺类化合物。通过添加类似产物的N-羟胺，观察到了前所未有的对映选择性的提高，使N-羟胺的对映选择性高达95%ee。

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.