Mechanistic details of metal-free cyclization reaction of organophosphorus oxide with alkynes mediated by 2,6-lutidine and Tf2O

Theoretical investigations have elucidated the mechanism of metal-free electrophilic phosphinative cyclization of alkynes reaction reported by Miura and coworkers. Two competitive mechanisms I and II were explored without or with 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 13.5 and 10.6 kcal/mol, respectively. Our calculation results suggested that the cumulative effect of the isomer of 2,6-lutidine and Tf2O as well as TfO- affects the title reaction to some extent, and simultaneously activates key reaction sites and reverses the polarities of them via the formation of abundant noncovalent interactions to decrease activation barriers of TSs. In addition, the effects of two series substituents on reactivity of phosphine oxide were investigated. Therefore, our study will serve as useful guidance for more efficient metal-free synthesis of organophosphorus compounds mediated by pyridine reagents.