Copper-catalyzed Synthesis of Silyl-substituted Enatioenriched Allenes

Author:Liu Zheng Li

Supervisor:luo de ping teckpeng lohxu yun he


Degree Year:2019





Chiral allenes are widely present in natural products and pharmaceutical compounds.They are increasingly used as fundamental materials for construction of complex organic products.Accordingly,in the past few decades,many efforts have been focused on the synthesis of multi-substituted functionalized chiral allenes.Among them,the silyl-substituted axially chiral allenes have attracted much attention because of their versatile reactivities.However,it is worth noting that synthesis of enantiomerically enriched chiral allenylsilanes via direct introducing silyl group to the products is less.Especially,rare examples on chiral homoallenylsilanes have been disclosed.In this thesis,the synthesis of silyl-substituted enatioenriched allenic compounds has been studied from the following two parts.Part Ⅰ:Copper-catalyzed silylation of propargyl dichlorides:access to functionalized allenylsilanes.Traditional methods for the synthesis of chiral allenylsilanes have some issues such as limited substrate scopes and harsh reaction conditions etc..In our work,a general copper-catalyzed mono-and disilylation reaction of propargyl dichlorides has been developed.In this protocol,racemic or optically active chloro-substituted allenylsilane products could be achieved under mild reaction conditions by tuning the chiral ligand.This reaction has good functional group compatibility and excellent enantioselectivity.Moreover,we carried out a detailed study on the transformation of chiral allenylsilane products and explored their synthetic value.Part Ⅱ:Synthesis of homoallenylsilanes via copper-catalyzed conjugate 1,4-protosilylation of enynes.Chiral homoallenylsilanes are an important class of chiral reagents,and only two cases have been reported about its synthesis.Therefore,it is necessary to develop new methods to synthesize enantioenriched homoallenylsilanes.In this study,we employed CF3-substituted 1,3-enynes with silylboronate as starting materials,and achieved chiral homoallenylsilanes successfully via copper-catalyzed asymmetric 1,4-protosilylation.The study has shown that this reaction has good substrate scopes,excellent enantioselectivity and high regioselectivity.Furthermore,the derivatization study showed that homoallenylsilane products could be converted to other useful fragments such as difluorosubstituted diene,alkenyl borate,homoallenyl alcohol,trifluoromethyl-substituted dihydrofuran.