Synthesis And Application Of Bridging Chiral P-t-butylcalix[4]arenes

Objectives : Bridging chiral calix[4]arenes are originated from asymmetrically substituted asymmetric substitutions on not only phenyl rings and(or)oxygen atoms but also bridging methylenes.It can be prospected that the exclusive bridging-point chirality will theoretically provide a good platform to construct specific chiral hosts and catalysts.However,the study of bridging chiral calix[4]arenes shows seriously insufficiernt.Until now,their applications in chiral recognition and asymmetric catalysis have not been reported.The asymmetric Henry reaction has emerged as a powerful synthetic tool for the stereoselective formation of carbon-carbon bonds.Currently,many chiral drugs contain the structure of 2-amino-1-aryl ethanol.Asymmetric Henry reaction is one of efficient approaches to synthesize them.Therefore,the purpose of this study is to synthesize bridging chiral calix[4]arenes with catalytical potential,and study their asymmetrical catalytic capacity in Henry reaction in order to obtain chiral organocatalyst for the synthesis of the intermediate of 2-amino-1-aryl ethanol.Methods: Bridging chiral p-t-butylcalix[4]arenes were synthesized from ortho-Fries rearrangement reaction,optically resolved with chiral auxiliary,and subsequently derivatized.The derivatives were applied as organocatalysts for their asymmetrical catalysis study.Results:(1)Bridging chiral p-t-butylcalix[4]arenes were synthesized from ortho-Fries rearrangement reaction,optically resolved with(1S)-(+)-camphor-10-sulfonyl chloride.A pair of diastereoisomers H-4-a and H-4-b were successfully separated by conventional silica gel column chromatography.(2)Three pairs of bridging chiral p-t-butylcalix[4]arenes H-6-a and H-6-b,y-6-a and y-6-b,w-7-a and w-7-b were successfully synthesized,and applied as chiral organocatalysts in Henry reaction for their asymmetrical catalysis study.The experimental results showed that the ee's in their catalysis were not satisfactory.Conclusions :(1)Bridging chiral p-t-butylcalix[4]arenes were synthesized from ortho-Fries rearrangement reaction.The racemate were optical resolved with chiral auxiliary.Compared to the reported methods of bridging chiral calix[4]arenes,the synthesis step was shortened and the yield was improved.(2)Three pairs of bridging chiral p-t-butylcalix[4]arene derivatives were successfully synthesized and applied as chiral organocatalysts in Henry reaction.The experimental results were not satisfactory,but can provide a beneficial guidance for subsequent research.