氮杂Mislow-Evans重排反应研究

立体选择性构筑C-O键是有机合成方法学的重要研究方向之一。本项目拟发展一种Mislow-Evans重排反应的新型氮杂变种，使用氮原子替换Mislow-Evans重排底物——烯丙基亚砜类化合物中的烯丙位碳原子，通过重排实现α-次磺酰氧基亚胺或类似物（亚胺酯或脒）的合成，拓展该类反应产物的多样性（切断氮杂重排产物中的硫氧键还可以得到相应的醇类化合物）。通过对各种潜在氮杂Mislow-Evans重排前体的构筑和重排反应的研究，总结其适用范围，了解影响反应化学选择性和立体选择性的因素并施以调控，最终开发出能够有效合成α-羟基亚胺及其类似物的合成方法。氮杂Mislow-Evans重排反应可以将制备重排前体的合成原料——手性亚磺酰胺中的氧原子转位到产物的手性羟基中，在一个无氧化剂存在的情况下实现亚胺及其类似物的不对称α-羟基化。该重排反应是对Mislow-Evans重排的重要拓展，具有重要的研究意义。

Stereoselective construction of C-O bond is an important research subject in synthetic methodology. This proposal aims to develop a novel aza variant of Mislow-Evans rearrangement reaction by using nitrogen atom to replace carbon atom at the allylic position in allylic sulfoxide, a substrate for Mislow-Evans rearrangement. The proposed aza-Mislow-Evans rearrangement could provide an access to the synthesis of α-sulfenyloxy imines or its analogs such as imidates or amidines, which would increase the diversity of the rearrangement products. Cleavage of the S-O bond in the product of aza-Mislow-Evans rearrangement leads to α-hydroxy imines or its analogs. Studies on construction of the precursors for the aza-Mislow-Evans rearrangement and the rearrangement itself including reaction scope and influence factors associating with chemoselectivity and stereoselectivity will lead to an effective synthetic methodology toward α-hydroxy imines or its analogs. The aza-Mislow-Evans rearrangement enables transfer of oxygen atom from enantioenriched sulfinylamide, a starting material for preparation of rearrangement precursors, into chiral hydroxyl group of products and allows asymmetric α-hydroxylation of imines or its analogs under non-oxidative conditions. This reaction significantly extends the traditional Mislow-Evans rearrangement and deserves extensive investigation.