Palladium-catalyzed Intramolecular Arylation To Synthesize Chiral Quinolinones And Indanone Compounds

Quinolinone and anthrone structure fragments are widely distributed in various natural products and drug molecules.This paper mainly focused on the synthesis of a-nitroquinolinone and anthrone compounds base on transition metal catalyzed arylation:Palladium-catalyzed intramolecular carbon-hydrogen activation and cyano desymmetry to synthesize quinolinone and anthrone compounds containing a quaternary carbon chiral center.1.The intramolecular C(sp3)-H activation of palladium catalyzes N-protected ?-nitroamide compounds to synthesize a-nitroquinolinone derivatives were investigated.Monophosphorus ligand tricyclohexylphosphine tetrafluoroborate and palladium acetate were used as a standard catalytic system to provide various substituted quinolinone compounds with up to 92%yields.The reaction has good compatibility with various substituted aryl substrates of methyl and PMB-protected amides,as well as a-trifluoromethyl and alkyl substituted amide substrates are compatible with the reaction system.2.With the optimization of different chiral ligands and further reaction conditions,the intramolecular enantioselective C(sp3)-H activation of a-nitroamide compound was achieved by using allylcyclopentadienyl palladium and TADDOL-derived phosphoramidite ligand,which afforded chiral quinolinone compounds.The universality of the asymmetric catalytic system for various substituted arylamide substrates was then investigated.Various chiral quinolinone derivatives can be synthesized with up to 90%yield and 98%ee,and the absolute configuration of the product was determined by single crystal diffraction.Further conversion of the product yields a more modified quinolinone compound in excellent yield.3.After exploring different types of substrates,2-(2-halobenzyl)propane cyanide was chosen as the standard substrate for the synthesis of chiral fluorenone or spirosterone compound under the pattern of palladium catalytic intramolecular desymmetrization of propylene dicyano.After screening for different chiral ligands and reaction conditions,chiral fluorenone compounds were obtained with a yield of 90%and 10%ee under the conditions of palladium acetate as a catalyst,TADDOL-derived phosphoramidite as a ligand,triethylamine as a base,formic acid as a proton source,and DMF as a solvent at 130?.