Temperature–dependent reaction rates of quinone-alkene cycloaddition reveal that only entropy determines the rate of SPOCQ reactions

Abstract

Second-order rate constants and thermodynamic activation parameters for the strain-promoted oxidation-controlled quinone (SPOCQ) click reaction of an ortho-quinone with various trans-cyclooctene and cyclooctyne reagents were determined by stopped-flow spectroscopic analysis. We substantiate the origin of the enhancements of the reaction rates in various sTCO derivatives as compared to TCO, and demonstrated that ortho-quinone-cycloalkene cycloadditions are fully entropy-controlled. The endo/exo differences of BCN in SPOCQ and SPAAC were also (re)evaluated, revealing absence of a difference in reactivity between these two isomers for both click reactions. Full crystallographic descriptions of endo-BCN-OH and DBCO combined with high-end DFT ring-strain computations confirm that entropy controls this reaction for both cycloalkenes and cycloalkynes alike.