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 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 deriva-tives 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 reac-tivity between these two isomers for these two 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 cyclo-alkenes and cycloalkynes alike.