Different Reaction Mechanisms Triggered by the Meta\nEffect: Photoinduced Generation of Quinone Methides from Hydroxybiphenyl\nDerivatives

A series\nof sterically congested quinone methides (QMs) exhibit\nphotoinduced antiproliferative activity against some human cancer\ncell lines. To elucidate the structure–reactivity relationship\nand details of mechanisms of the photogeneration of sterically congested\nQMs, we chose phenylphenol derivatives <b>1</b>–<b>3</b> as QM precursors and investigated their photo­dehydration\nprocesses in aqueous solutions using ultrafast spectroscopy and theoretical\ncomputations. We found that <i>meta</i> derivatives <b>1</b> and <b>2</b> undergo water-mediated excited-state\nproton transfer (ESPT) from the phenol OH, followed by expulsion\nof the OH<sup>–</sup> to form QMs. By comparison, <i>para</i> derivative <b>3</b> proceeds via water-mediated ESPT from\nH<sub>2</sub>O to benzyl alcohol coupled with dehydration as the first\nstep, delivering a cation intermediate, which further deprotonates\nto yield QM. Such results would help chemists understand more about\nthe <i>meta</i> effects in photochemistry and about ESPT\nand would help synthetic chemists design sterically congested QM precursors\nwith extraordinary reactivities and expand applications of QMs in\nbiological and medical systems.