高张力的2-亚甲基环丁醚是重要的有机合成子,是很多具有生物活性天然产物的重要结构片段,它的合成及性质研究是有机合成中的难点和热点问题。本项目研究的是2-亚甲基环丁醚合成及不对称开环反应,具体包括如下几个方面：(1)建立基于1，10-邻菲咯啉、2，2'-联吡啶和1，1'-联异喹啉等化合物为骨架的配体库，开展CuI催化的烯基氯的4-exo型分子内C-O偶联反应研究；(2)开展高挑战性含氟、稠环式、α,β-不饱和式和手性2-亚甲基环丁醚合成研究；(3)研究手性路易斯酸或有机小分子催化的不对称2-亚甲基环丁醚开环反应。具体包括手性铝试剂催化的不对称杂Claisen重排反应、手性(salen)Co(III)或手性二磺酰胺催化的分子内不对称开环反应、手性配体或手性离子诱导的Pd催化的不对称开环合成环丁酮反应。

Highly strained 2-methyleneoxetane is a kind of very important synthons and structural motif in many biologically active natural products.The synthesis and transformation of 2-methyleneoxetanes are not only hot topics but also tough projects in organic synthesis. This proposal focuses on the synthesis of 2-methyleneoxetanes and their application in asymmetric ring opening reactions. The proposal could be detailed as the following parts: (1) With 1,10-phenthroline, 2,2'-bipyridine, or 1,1'-bisisoquinone as the backbone, a ligand library would be set up and could be served as the lignd candidate for the CuI-catalyzed intramolecular C-O cross coupling reaction with 4-exo mode cyclization. (2) A series of 2-methyleneoxetanes with great challenge would be explored, including fluorine substituted, fused type, α,β-unsaturated,and chiral version.(3)Asymmetric ring opening reactions of 2-methyleneoxetane catalyzed by chiral Lewis acid or organocatalyst would be also investigated.These ring opening reactions include asymmetric aza-Claisen rearrangement reaction catalyzed by chiral aluminium reagent, asymmetric intramolecular ring opening reaction catalyzed by chiral (salen)Co(III) or chiral disulfonimide, and synthesis of chiral cyclic butanone via Pd-catalzyed ring opening reation with chiral ligand or counterion for the chiral induction.