The Synthesis Of Bisimidaolines Ligands With Biaryl Backbone And Their Application In The Asymmetric Friedel-Crafts Alkylation Reaction

This paper discusses the synthesis and characterization of chiral bisimidazoline ligands with biaryl backbones and their application in the asymmetric Friedel-Crafts alkylation of indoles with nitroalkenes. The main research contents are as follows: 1. Synthesis of chiral ligands 8d-f3,5-Dimethyl benzoic acid reacted with bromine to get 2-bromine-3,5-dimethyl benzoic acid 5a. Then compound 5a and 5b respectively reacted with SOCl2, followed by reacting with amino alcohols at room temperature in the presence of Et3 N in CH2Cl2, to afford the corresponding amido alcohols 6a-f. Final products 7a-f were obtained from compounds 6a-f and primary amine, as shown in scheme 1. The new compounds 6a-c, 7a-c were all fully characterized by 1H NMR, 13 C NMR, IR and HRMS.The axially chiral ligands 8a-c were obtained from a mixture of 7a-c and freshly activated copper in dry DMF which were heated at reflux under argon atmosphere for 24 h(Scheme 2). Single diastereomers 8a-c were obtained after isolated from column chromatography. The new compounds 8a-c were all fully characterized by 1H NMR, IR, 13 C NMR and HRMS. 2. The application of ligands 8a-f in the asymmetric Friedel-Crafts alkylation reactions.We investigated the application of compounds 8a-f as chiral catalyst in the asymmetric Friedel-Crafts alkylation reactions of trans-nitrostyenes and indoles(Scheme 3). The optimized reaction condition sited as 10 mol% Zn(OTf)2, 11 mol% 8d, in CH2Cl2 at 40 oC for 48 h under argon atmosphere, giving the product in a good yield(98%) and moderate enantioselectivity(37% ee). We then explored the scope of the alkylations of indoles with nitroalkenes at the optimized conditions. Good yields(up to 99%) and moderate enantioselectivities(up to 57% ee) were obtaineded.