Studies On Reactivity Of Phosphonochloridates And Unsaturated Systems

Organophosphorus compounds,as significant organic synthesis units,catalytic ligands and biologically active intermediates,have been got much attention due to their wide application in the fields of optoelectronic materials,homogeneous catalysis,pharmaceuticals,and pesticides.Therefore,the development of efficient synthetic methods for such compounds is of great value in organic chemistry and medicinal chemistry.The thesis focuses on the reactivity of cheap and easily available phosphonochloridates as the phosphonyl-carbon source,and a series of unsaturated molecules such as ?,?-unsaturated ketones,imines,unsaturated imines and isothiocyanates for the syntheses of unsaturated-?phosphonolactones,?,?-unsaturated phosphonamidates,benzo-?phosphonolactams with structural diversity under transition metal-free catalysis in the one-pot fashion.Moreover,wide substrate scope,excellent functional group tolerance,and mild conditions manifeste advantages of these methods.At the same time,these novel methodologies answer the question whether phosphonochloridates can transform to phosphene intermediates under basic conditions.Some researches as follows:(1)An efficient and high-diastereoselective synthesis of polysubstituted unsaturated-?-phosphonolactones with continuous stereocenters based on alkylphosphonochloridates and ?,?-unsaturated ketones was developed.In the hypothesis,the phosphono carbanion,generated by treatment of the alkylphosphonochloridates with base,could react with chalcones via the Michael addition,followed by the subsequent intramolecular addition-elimination process.The domino annulation realizes the formal[2+4]cycloaddition of alkylphosphonochloridates and unsaturated ketones,at the same time,avoiding the problems of substrate pre-functionalization,excessive use of oxidants,and transition metal catalysis in the traditional methods.Finally,the synthetic route novelly uses phosphonyl-carbon building blocks to synthesize ?-phosphonolactone molecules with potential enzyme inhibitors showing important synthetic value and theoretical significance.(2)The novel synthesis of ?,?-unsaturated phosphonamidates,starting from alkyl ethylphosphonochloridates and dibenzo[b,f][1,4]oxazepine compounds is developed via the electrophilic hydrophosphonylation of cyclic imines.In the scheme,initially,the alkyl ethylphosphonochloridates react in acylation of the cyclic imines to access to the phosphonyliminium salts.Deprotonation under basic conditions and 1,5-hydride transfer process undergo successively,realizing the construction of the C=C double bond and the reductive hydrogenation of imines.It is worth mentioning that the process of deprotonation is the key driving force of the reaction.This method creatively uses phosphonyl-carbon building blocks via the"phosphonylation/deprotonation" strategy,to obtain valuable ?,?unsaturated phosphonamidate compounds in the one-pot fashion with high yield and high regioselectivity,which inspired thinking on the synthetic methodology of constructing unsaturated compounds.(3)Based on the "phosphonylation/deprotonation" strategy,the protocol for the preparation of N-allyl substituted ?,?-unsaturated phosphonamidates from alkyl ethylphosphonochloridates and ?,?unsaturated linear imines with high regioselectivity is realized via acylation,deprotonation,and 1,5-hydride transfer steps.It is worth mentioning that the obtained products can undergo olefin metathesis(RCM)reaction to obtain valuable ?-phosphonamidate compounds.In addition to unsaturated imines,N-alkyl linear imines can also react smoothly.(4)Based on aryl methylphosphonochloridates and cyclic imines,the en-riched benzo-?-phosphonolactam compounds are synthesized without the involvement of transition metal catalysts in one-pot under the strategy of "phosphonylation/deprotonation".In the presence of KHMDS as the base,the phosphonylation ion-pair intermediates acylated by cyclic imine and aryl methylphosphonochloridates,undergo deprotonation at their ?position.Due to the resulting carbanion intermediates,the connected aromatic ring is more electron-rich,which inducing the tandem reaction of intramolecular Friedel-Crafts alkylation and aromatization,affording formal[4+2]cycloaddition products.This method expands the prospect of applying phosphonyl-carbon building blocks to the synthesis of novel phosphonolactone compounds through the "phosphonylation/deprotonation" strategy.(5)To facilitate the research on the reactivity of isothiocyanates and phosphonochloridates,an efficient and green method to synthesize isothiocyanates in water phase is developed.In the presence of carbon disulfide and potassium carbonate,primary amines as raw materials are converted to potassium dithiocarbamates in the water phase,quickly and efficiently affording isothiocyanates with diverse structures followed by the treatment with green inorganic oxidant sodium persulfate.In the process,the dithiocarbamates are subjected to an oxidizing agent,generating carbamothiony radical intermediates in stiu,then a free radical elimination process occurs under basic condition to obtain the target products.Basic conditions are necessary for good chemoselectivity for isothiocyanates.In addition,chiral isothiocyanates can be smoothly got with preserving chirality in one step from optically active primary amines.Good industrial application prospects and potential applicability are displayed in the gram scale and derivatization experiments.The advantages of environmental friendliness,wide substrate range,good functional group tolerance,high yield,mild conditions,and high application value have greatly attached tag on the method.(6)Based on the reactivity of isothiocyanates and phosphonochloridates under the "phosphonylation/deprotonation" strategy,The phosphonyl-carbon unit is introduced into the preparation of ?phosphonolactam.Preliminary studies on it are carried out,drawing the following conclusions:Isothiocyanates,under strong base conditions,are easily decomposed into the corresponding amines.And the its nitrogen atom is less nucleophilic,so it is not easy for phosphonochloridates to undergo phosphonylation and deprotonation process with them.Fluorenyl phosphonochloridate and diphenylmethylphosphonochloridate are selected as ideal candidates to react with alkyl isothiocyanates under the relatively weak base conditions,such as in the presence of triethylamine or pyridine,but the followed research is on the way.In summary,the thesis studies on reactivity of the cheap and easily available phosphonochloridates and common unsaturated systems,systematically illustrating that phosphonochloridates are different from acyl and sulfonyl chlorides and have unique reactivity properties.That is,the alkyl phosphonochloridates does not participate in the construction of phosphoryl compounds in the form of phosphene intermediates but phosphonyl carbanions under basic conditions.These results have important significances for the development of organophosphorus chemistry.In addition,based on the "phosphonylation/deprotonation"strategy developed in this thesis,we use phosphonochloridates as the phosphonyl-carbon source for the development of synthetic methods for diverse phosphoryl compounds with important reference values.