Mechanistic Insights On Metal-Free-Catalyzed C-P Bond Formation Via Phosphorylation Of Alkyne Or Isothiocyanate

Organophosphorus compounds are indispensable synthetic reagents and catalysts in organic chemistry,and they are widely used in biologically active substances and organic functional materials.In the past few decades,a lot of research has been performed on the effective synthesis strategy for constructing C–P bonds and the design of reaction conditions for the synthesis of organophosphorus compounds to achieve economic and efficient synthesis.However,the related theoretical research is relatively scarce.Therefore,we investigate the representative reaction systems of constructing C-P bond under two kinds of metal-free catalysis conditions based on density functional theory(DFT),in order to reveal the influence of reaction conditions on the mechanism and its key role.The main research contents are as follows:1.The DFT theory was applied to study the phosphination cyclization reaction mechanism of diphenyl phosphorus oxides and alkynes,promoted by 2,6-lutidine and Tf2 O under metal-free conditions.Two competitive mechanisms I and II were explored without or with including 2,6-lutidine.Both of I and II involve transformation of P(V)to P(Ⅲ),electrophilic addition,ring opening and cyclization/cyclization,hydrogen-transfer,and oxidation.The rate-determining step of mechanism I and competitive less-step II is electrophilic [2+1] cycloaddition and electrophilic addition via single C–P bond formation with activation barrier of 13.5and 10.6 kcal/mol respectively.Our calculation results shown that the cumulative effect of the isomer of 2,6-lutidine and Tf2 O as well as Tf O–affects the title reaction in some extent,and simultaneously activates key reaction sites and reverses the electrical properties of them via the formation of abundant NCIs to low activation barriers of TSs.In addition,effects of the substituent on reactivity of phosphine oxide were investigated.Therefore,our study will serve as a useful guidance for more efficient metal-free synthesis of organophosphorus compounds mediated by pyridine reagents.2.The reaction mechanism of isothiocyanates and diaryl phosphine oxide to synthesize bisphosphinoylaminomethanes was investigated by DFT calculations under solvent-free and metal-free conditions.According to the different binding modes of the reaction substrates,two mechanisms were mainly elucidated,which are competitive with each other.Mechanism 1 is slightly favored than mechanism 2.Compared with mechanism 1,mechanism 2 omits the multi-step hydrogen transfer process and generates directly H2 S.In the important electrophilic addition stage,the rate-determining step of these two mechanisms is the first electrophilic addition with the activation energy barrier of 16.2 and 17.5 kcal/mol,respectively.In these two mechanisms,diaryl phosphine oxide as substrate and proton shuttle not only promotes the hydrogen migration steps,but is also reduced to the form of P(Ⅲ)to participate in the reaction.Our results provide a theoretical basis for the design and simple synthesis of organophosphorus compounds containing bis-C-P.