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

Second-order rate constants and thermodynamic activation parameters for the strain-promoted oxidation-controlled quinone (SPOCQ) click reaction of an <i>ortho</i>-quinone with various <i>trans</i>-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 <i>ortho</i>-quinone-cycloalkene cycloadditions are fully entropy-controlled. The <i>endo/exo</i> 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 <i>endo</i>-BCN-OH and DBCO combined with high-end DFT ring-strain computations confirm that entropy controls this reaction for both cycloalkenes and cycloalkynes alike.