Synthesis Of Cyclopentane 1,2-bisphosphine Compounds & One-pot Synthesis Of Heteroaromatic Acetals

The development of different strategies to construct heteroatomic compounds has always been an important research direction in chemical synthesis,among which organophosphine compounds and aromatic aldehyde compounds have wide applications in molecular catalysis,medicinal chemistry and materials science.Therefore,we are committed to the research of cyclic bisphosphite compounds and heteroaromatic acetal compounds with added value,and explore and optimize their synthesis methods to make their synthesis more efficient and faster.The main content of the paper includes the following two parts:the first part is the synthesis of cyclopentyl 1,2-bisphosphine compounds;The second part is the synthesis of heteroaromatic acetals by a pot method of methyl 2-methylquinoline-2-carboxylate and methanol.The first chapter first introduces the research progress in bisphosphine ligand synthesis in recent decades and its application in the field of asymmetric catalysis,and then focuses on the development and application of several special 1,2-bisphosphine ligands.1,2-bisphosphine ligands are widely used in asymmetric catalysis,but the synthesis of such ligands is challenging,often requires multi-step synthesis,poor atomic economy,and partially limited structural diversity.The research content of the first chapter is to find an effective method for synthesizing DPCP-type ligands from easily available malonates and dienylphosphine oxides that can modulate both the backbone and phosphine substituents,which can rapidly synthesize various cyclopentane 1,2-bisphosphine compounds.Taking dimethyl malonate and2,3-bis（diphenylphosphino）-1,3-butadiene as model substrates,through the screening of base,temperature and solvent,the best reaction conditions were malonate（0.1 mmol）,1,3-butadiene（0.1 mmol）,NaOH（0.2 mmol）,1,2-dichloroethane（1 mL）were added to 4 mL reaction flask sequentially,and the reaction system was stirred at 45℃ for 1 h,cyclopentane 1,2-diphosphorus compounds.Asymmetric malonates also react smoothly,and these products will allow further selective functionalization of ester groups.The highlight of this method is that the asymmetric synthesis of bisphosphine ligands can be accomplished by simply introducing a menthol group as a chiral aid to malonates.The resulting phosphine oxides can be selectively reduced to obtain the desired bisphosphine ligands,which are converted into corresponding transition metal complexes such as Pd,Pt,and Ni,which have a wide range of applications in asymmetric catalysis.This second chapter highlights that aromatic aldehydes are an important class of organic compounds widely found in nature,which are widely used in drugs,materials and medical devices,and can participate in a variety of chemical reactions.N-Heterocyclic aromatic aldehydes are a key structure of drugs and agrochemicals,and unlike benzene,quinolines have a relative lack of electrons,making electrophilic formylation more difficult.Since the Minisci reaction is a convenient way for the alkylation of heteroaromatic hydrocarbons,a Minisci reaction for the synthesis of aromatic acetals was developed by selective domino reaction of methyl quinoline-2-carboxylate using Ag（I）as a catalyst.Using methyl quinoline-2-carboxylate as the model substrate,the optimal reaction conditions were methyl quinoline-2-carboxylate（0.2 mmol）,AgNO₃（0.04 mmol）,Selectfluor（0.8 mmol）,methanol（12 mL）were added to a 35 mL reaction flask sequentially,and the reaction system was stirred at 80℃ for 24 h.Heteroaromatic acetals can be obtained at yields of 30%-78%.The reaction showed good tolerance to various substituents such as halogens,methyl groups,and CF₃,and polysubstituted quinoline compounds could also be reacted smoothly.The highlight of this method is that the HF generated in situ plays an important role and does not require additional acids.Mechanistic studies have shown that this is a free radical reaction process,and the capture of hydrogen is the rate-determining step of the reaction.