Asymmetric Friedel-crafts Alkylation Of Indole With Nitroalkenes

Indole ring is one of the most widely heterocycles and ubiquitous substructural motifs found in many biologically active molecules and natural products,thus the synthesis of indole derivatives has been a focused interest for organic chemists.Asymmetric Friedel-Crafts reaction of indole with nitroalkenes is an important method for the synthesis of indole derivatives.The nitro-group containing indole derivatives obtained from the reaction can be further converted to some active compounds.Therefore,it's highly important to realize such catalytic and stereoselective Friedel-Crafts reactions.1.The enantioselective alkylation reaction of indoles with a-substituted-?-nitroacrylates was studied and the optimal reaction conditions were found after the scanning of Lewis acid,bisoxazoline ligand,solvent,temperature and so on.With 1 mol%of Ni-bisoxazoline complex,the reaction proceeds efficiently in toluene at 50?,giving the yield from 43%to 98%and the enantioselectivity from 54%to 97%,and providing a reliable access to the potential biologically active ?-tryptophan derivatives bearing all-carbon quaternary stereocenters.2.Highly enantioselective alkylation reaction of 3-methyl indole with nitroolefins was studied.The optimal reaction conditions were found after the screening of Lewis acid,chiral ligand,solvent as well as the temperature,the optimal condition is discovered.With 6 mol%bisoxazoline ligand L3-8 and 5 mol%Zn(OTf)2,the reaction proceeds efficiently in toluene at 80?,giving the yield from 70%to 99%and the enantioselectivity up to 93%.