Different Reaction Mechanisms Triggered by the Meta Effect: Photoinduced Generation of Quinone Methides from Hydroxybiphenyl Derivatives

A series of sterically congested quinone methides (QMs) exhibit photoinduced antiproliferative activity against some human cancer cell lines. To elucidate the structure-reactivity relationship and details of mechanisms of the photogeneration of sterically congested QMs, we chose phenylphenol derivatives 1-3 as QM precursors and investigated their photodehydration processes in aqueous solutions using ultrafast spectroscopy and theoretical computations. We found that meta derivatives 1 and 2 undergo water-mediated excited-state proton transfer (ESPT) from the phenol OH, followed by expulsion of the OH^- to form QMs. By comparison, para derivative 3 proceeds via water-mediated ESPT from H₂O to benzyl alcohol coupled with dehydration as the first step, delivering a cation intermediate, which further deprotonates to yield QM. Such results would help chemists understand more about the meta effects in photochemistry and about ESPT and would help synthetic chemists design sterically congested QM precursors with extraordinary reactivities and expand applications of QMs in biological and medical systems.