Synthesis And Application Of Bridging Chiral Calix[4]Arenes

Objectives:Because of its unique structure,various calixarenederivatives have been widely used in molecular recognition, phase transfer catalysts, molecular catalysis, enzyme models and chemical sensors.Over the past few decades, researchers have mostly laid stress on the research of inherently chiral calix[4]arenes andthe synthesis and resolutionof the inherently chiral calix[4]arenesbecome highlyefficient and applicable. However, their applications in asymmetric catalysis areunsatisfactory since the stereo selectivities in asymmetric catalysisare comparably low. Compared to inherently chiral calix[4]arenes, the representative characteristics of bridging chiral calix[4]arenes is that bridging point chirality exists on their asymmetrically substitutedbridging methylenes, which can be modified throughnot only changing the calix[4]arenesubstituents but also changing the calix[4]arene conformation. The unique characteristics of bridging chiral calix[4]arenewill provide versatile ways to construct specific chiralhosts and catalysts. Now, the research ofbridging chiral calix[4]arenesare in a preliminary stage. Therefore, one task of our research was toexplore aneffecientapproachto synthesize optically pure bridging chiral calix[4]arenesfrom optically pure inherently chiral calix[4]arenes, which will provide asubstantial foundation for their applications in asymmetric catalysis. Currently, a lot of chiral drugs have the structure of 2-amino-1-aryl ethanol. The Henry reaction is a crucial step in their synthesis. At present, the catalysts for this reaction are mainly chiral metal complexes. Organocatalysts are low-molecular-weight organic molecules whose advantages are cheap, stable and low toxic. Therefore,another purpose of the study wasto prepare more efficient organocatalyst for asymmetric Henry reaction through modification of optically pure bridging chiral calix[4]arenes, which will provide a more economic approach to 2-amino-1-aryl alcohol chiral drugs. Methods : In our research,a pair of inherently chiral p-tert-butylcalix[4]arenes andanother pair of inherently chiral debutylcalix[4]arenes were synthesized and resolved according to the reported synthesis approaches about inherently chiral calix[4]arenes.Inherently chiral calix[4]arenes were thenmodified into bridging chiral calix[4]arenesthroughortho-Fries rearrangement reaction. Subsequently, bridging chiral calix[4]areneswere used as organocatalysts to catalyze Henry reaction.Finally, bridging chiral calix[4]areneswere deeply modified into more efficient organocatalysts based on the feedback of theircatalysis results in asymmetric Henry reaction.Resultes: Two pairs of bridging chiral calix[4]arenes have been synthesized. One is bridging chiraldebutylcalix[4]arenes such as d-a-1,d-a-2,d-b-1 and d-b-2, the other isbridging chiralp-tert-butylcalix[4]arene such as a-1,2a-2,2b-1 and 2b-2. Due to the more availability of2a-1, it was thendeeply modified into 1-2a-1.The catalytic performance of 1-2a-1 was tested through catalyze Henry reaction. However, the results show that its catalytic effeciency is not satisfactory, which may be attributed to its unrigid skeleton. Therefore, 1-2a-1 wasmodified into2-2a-1 and 2-2a-2based on its catalysis feedback.Conclusions:In our research, bridging chiral debutylcalix[4]arenes and bridging chiral p-tert-butylcalix[4]arenes were synthesized from the correspondinginherently chiral calix[4]arenes throughortho-Fries rearrangement reaction, which provided a novel approach to synthesize bridging chiral calix[4]arene from inherently chiral calix[4]arenes. Moreover, the more available bridging chiral p-tert-butylcalix[4]arenes were modified into preliminary chiral organocatalysts. Their catalytic performances in asymmetric Henry reaction were tested. The bridging chiral calix[4]arene catalysts were deeply modified based on their catalysis feedback, which provided a prerequisite for more efficientorganocatalysts.