PCET beyond Simple pKa-Related Base Effects: Unlocking Inaccessible Substrates for Direct Intermolecular Photocatalytic Ring-Opening Remote Alkylative C-C Functionalization of Cycloalkanols

Herein, we report the redox-neutral photocatalytic cascade transformation of cyclic alcohols to terminally C(sp3)-C(sp3)-coupled, functionalized open-chain products. Initial key step of this operationally simple and broadly applicable methodology is the base promoted, oxidative multisite proton coupled electron transfer (MS-PCET) activation of strong O-H bonds under metal-free photocatalytic conditions with visible light. Importantly, through the targeted modulation of the base, our method allows the application to previously inaccessible, non-activated substrates and thus exceeds the application range of typical e-rich arene (para-methoxyphenyl (PMP) etc) containing derivatives. NMR-based mechanistic studies using in-depth H-bond analysis and DOSY experiments have elucidated the crucial role of the (pyridine) base in this multisite PCET, which exceeds typical pKa-related and/or steric effects. Our gained insights into the key importance of additional weak interactions to promote a pivotal productive alcohol-base pre-organization were directly put into practize to pioneer the successful remote alkylative Giese-type C-C-bond formation of formerly challenging alkyl-substituted cycloalkanols.