Studies On The Tandem Reactions Of Enamine Compounds

Enamines are important structural units of organic compounds and are widely found in natural products and drug molecules.Because of its prepreration simplicity and multiple reactive sites,enamines were widely used in the field of organic synthesis.In this thesis,we mainly focused on the studies on tandem reactions of enamine compounds.1)Pyrrolo[3,4-c]-quinolin-l-one derivatives were synthesized via a one-pot multi-step tandem reaction.This reaction included an Au(I)-catalyzed selective a-Csp2-H functionalization of the enaminones with diazoindolinones and TsOH catalyzed rearrangement-cyclization.The synthetic methodology has some advantages such as mild reaction conditions,good substrate compatibility and excellent chemo-and regioselectivity.With Au(I)catalysis,N-H insertion reactions were avoided effectively.In addition,a series of a-Csp2-H functionalized enaminones could also be isolated after single gold catalysis step.2)Based on our first work,with N-Ts enaminones as the starting materials,Ph3PAuNTf2 as the catalyst,HCIClcon.as the promotor,a novel tandem reaction was realized to synthesize 1-alkyl-3-(2-oxo-2-aryl/alkyl-ethyl)indolin-2-ones.This procedure includes Au(I)-catalyzed selective C-H functionalization and Br(?)nsted acid-mediated selective C=C bond cleavage of enaminones.Control experiments suggested that the cleavage process was significantly promoted by Bronsted acid.With ESI-MS analysis during the reaction process,the characteristic signals of conjugate addition intermediate,which was generated by nucleophilic attack of H2O to functionalized enaminones,was trapped.This result further supported the possible reaction mechanism.3)Pyrroles are special cyclic enamines and exist in drugs and natural products widely.The tandem reactions using pyrrole derivatives as the starting materials could facilitate the introduction of pyrrole blocks into complex molecules.With N-propargyl 1,2,4-trisubstituted pyrroles and alkynones as the starting materials,low-cost ZnI2 as the catalyst,a series of novel pyrrolo[1,2-a]azepine derivatives were prepared.This tandem reaction contains a Zinc(?)catalyzed conjugate addition and a selective endo-cyclization.The synthetic method provides an alternative solution for the formation of pyrrolo[1,2-a]azepine structure,which is widely found in natural products,drug molecules and their analogs.This method also has several advantages,such as high functional group tolerance,good to excellent yields and compatibility to air.4)With 1,2-disubstituted pyrroles and alkynones as starting materials,inexpensive and easily accessible silica gel as the promoter,the selective synthesis of 4,6-dicarbonyl indoles was realized.The tandem reaction includes the silica gel promoted conjugate addition,regioselective Diels-Alder reaction and oxidation process in air.Good to excellent selectivity and moderate to good yields could be obtained.Common methods to synthesize indoles usually involve a pyrrole ring construction from functionalized benzene precursor.Our method features a construction of benzene ring from pyrrole derivatives and provides a novel and efficient option to synthesize indoles.5)3-Alkenyl indolines were synthesized via a tandem reaction of organoborons and pre-functionalized substrates that bearing propargyl carbonate and tertiary amine moieties.This procedure includes a Pd(0)catalyzed allenylation and a tertiary amine self-catalyzed Csp3-H functionalization.Control reactions suggested that the substrate itself might also serve as a pivotal Lewis base for the N-benzylic Csp3-H functionalization.This tertiary amine self-catalysis mode provides an attractive reference for the substrates design to reduce the dependence on extrinsic reagent.