Synthesis And Application Of Amino Substituted Bridging Chiral P-tert-Butylcalix[4]arenes

Objective:The acquisition of chiral substances,in addition to nature's natural products,artificial synthesis is its main route.Although hundreds of excellent chiral catalysts have been synthesized,none of the ligands or catalysts is versatile.Therefore,the design and synthesis of novel chiral ligands or catalysts are an eternal theme in chiral catalysis research.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.Now,bridging chiral calix[4]arenes with a formamidyl substituent on bridging methine were frequently studied.However,the asymmetric catalysis of this type of bridging chiral calix[4]arenes is still unsatisfactory.In this thesis,the main aim is to develop an efficient method to construct bridging chiral calix[4]arenes with a nitro substituent on bridging methine,and then synthesize bridging chiral calix[4]arenes with an amino bridge-substituent.Subsequently,their asymmetric catalysis on Henry reaction will be studied in order to obtain chiral organocatalysts which can efficiently catalyze the synthesis of chiral medical intermediate with a structure of 2-amino-1-aryl ethanol.Methods:The bridging methylene nitrification of p-tert-butylcalix[4]arene was synthesized with tert-butyl nitrite as green nitrating agent,and the influence factor of the reaction was systematically explored.Bridging chiral calix[4]arenes with an amino bridge-substituent was produced after the reduction of its nitro precursor,and optically resolved with Boc-L-phenylalanine and?1S?-?+?-camphor-10-sulfonyl chloride as chiral auxiliaries.Finally,their asymmetric catalytic capability was examined in Henry reaction.Results:Bridging chiral calix[4]arenes with nitro bridge-substituent were successfully constructed through bridging methylene nitrification with tert-butyl nitrite as nitrating agent.Bridging chiral calix[4]arene racemate with an amino bridge-substituent?a-3?was produced after the reduction of its nitro precursor,and optically resolved into a pair of enantiomers?a-3-a and a-3-b?with Boc-L-phenylalanine as chiral auxiliary.Finally,their asymmetric catalytic capability was examined in Henry reaction between nitromethane and p-nitrobenzaldehyde as a model reaction.Although their catalytic results obtained at present are not very satisfactory(ee_max,25.1%),it has a certain improvement compared to that(ee_max,13.4%)of bridging chiral calix[4]arene tetrahydroisoquinoline synthesized in the previous stage of our research group.Conclusion:Bridging chiral calix[4]arenes with nitro bridge-substituent were successfully constructed through bridging methylene nitrification with tert-butyl nitrite as nitrating agent,which achieves the direct connection between a catalytic active group and the chiral center of bridging chiral calix[4]arene and brings a novel way to construct calix[4]arene bridging chirality.Preliminary asymmetric catalysis studies of bridging chiral calix[4]arene with an amino bridge-substituent shows that they can provide a comparably satisfactory catalysis result,which proves that the direct connection between the catalytic active group and the chiral center brings a benifical effect on their catalytic properties.A wider application of bridging chiral calix[4]arene with an amino bridge-substituent in asymmetric catalysis can be envisioned based on their superior structure.