Cassera Elena, Martini Vittoria, Morlacci Valerio, Abrami Serena, Della Ca' Nicola, Ravelli Davide, Fagnoni Maurizio, Capaldo Luca
PhotoGreen Lab, Department of Chemistry, University of Pavia, viale Taramelli 12, Pavia 27100, Italy.
SynCat Lab, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, Parma 43124, Italy.
JACS Au. 2025 Jun 16;5(7):3491-3499. doi: 10.1021/jacsau.5c00530. eCollection 2025 Jul 28.
Photocatalyzed hydrogen atom transfer (HAT) is now an established methodology in the synthesis of pharmaceuticals and agrochemicals as well as in the development of late-stage functionalization campaigns. Yet, the realization of the full potential of this manifold is held back by intrinsic challenges that still demand meticulous exploration and resolution, such as the lack of regioselectivity and inefficiency. Herein, we address these limitations by proposing a decarbonylative strategy. The fast direct HAT from aldehydes formyl group and ensuing α-fragmentation of the photogenerated acyl radical (i.e., decarbonylation) is exploited to boost efficiency, redirect regioselectivity, and enable reactivity in methodologies based on HAT. We validated this concept for decarbonylative C-C bond formation. In-depth mechanistic investigation based on laser-flash photolysis and density functional theory highlights the crucial role of kinetic factors in controlling the observed chemistry. Our work demonstrates that the exceptional hydrogen atom-donating ability of aldehydes can be harnessed to redefine paradigms in HAT photocatalysis.
光催化氢原子转移（HAT）如今已成为药物和农用化学品合成以及后期官能团化反应开发中的一种既定方法。然而，这一方法的全部潜力尚未得到充分发挥，因为仍然存在一些内在挑战，需要进行细致的探索和解决，例如区域选择性不足和效率低下等问题。在此，我们提出一种脱羰策略来解决这些限制。利用醛基的快速直接氢原子转移以及随后光生酰基自由基的α-碎片化反应（即脱羰反应）来提高效率、重新引导区域选择性，并在基于氢原子转移的方法中实现反应活性。我们验证了这种用于脱羰碳-碳键形成的概念。基于激光闪光光解和密度泛函理论的深入机理研究突出了动力学因素在控制所观察到的化学反应中的关键作用。我们的工作表明，可以利用醛类卓越的氢原子供体能力来重新定义氢原子转移光催化的范式。
