Studies On Highly Enantioselective Cu-Catalyzed Three-Component Cyclopropene Alkenylamination

Cyclopropane is an important structural fragment of organic molecules and an important structural unit of many bioactive compounds and natural products.In particular,enantiomeric cyclopropane with nitrogen atom substitution exists in many natural products and biosynthetic intermediates.However,the enantioselective synthesis of aminocyclopropane with three stereoscopic centers is still a great challenge.The synthesis of chiral aminocyclopropane are limited to specific structural features and require multiple steps.There are four main strategies:(1)multiple step process with Curtius rearrangement as a key step,(2)reaction between diazo compounds and nitrogen substituted olefin,(3)titanium-mediated reaction of amide and nitrile,and(4)metal-catalyzed functioalization of cyclopropylene.In this thesis,the Cu-catalyzed highly enantioselective three-component cyclopropene cis-alkenylamination with alkenyl boronic esters and electrophilic amination reagents hydroxylamine O-benzoates is presented.High enantiocontrol is realized with a commercial chiral phosphorus ligand,(R,R)-Ph-BPE.The reaction enables concomitant establishment of up to all the three stereogenic centers via desymmetrization.The introduction of alkenyl groups provides a possibility for further elaboration.At the same time,the reaction enriches the diversity of cyclopropylamine analogues for further study of their biological activities.Notably,an unusual diastereoselectivity pattern was observed for cyclopropenes bearing an ortho-substituted phenyl at 3-position,favoring addition at this apparently more sterically hindered side.DFT calculation was performed to rationalize this observation.