Diversifying Trityl Radicals via Oxidative Radical-Polar Crossover in Tandem with Aromatic Nucleophilic Substitution

Tetrathiatriarylmethyl (trityl) radicals are key spin probes for electron paramagnetic resonance (EPR) spectroscopy and crucial building blocks for high-performance dynamic nuclear polarization (DNP) agents. However, their applications have been limited by complex synthesis and structural modifications. In this study, we address this limitation by developing an oxidative radical-polar crossover (ORPC) strategy for trityl derivatization. This approach utilizes oxidization of trityl radicals by nitrosyl tetrafluoroborate (NOBF₄) to the corresponding trityl carbocations, which subsequently undergo aromatic nucleophilic substitution (S_NAr) with a diverse range of nucleophiles to afford various trityl derivatives. This method exhibits several notable advantages: (1) wide substrate scope, compatible with N-, S-, P-, and C-centered nucleophiles, including water-sensitive organozinc reagents; (2) high regioselectivity for monofunctionalization of a single aryl ring, avoiding statistical reaction mixtures; (3) iterative ORPC reaction which enables the synthesis of both symmetric trityls with three identical substituents and asymmetric trityls with three distinct substituents; (4) significantly improved yields which are 1.5-2 fold higher than those reported in the literature. This straightforward approach provides a powerful tool for tailoring trityl radicals to advance their applications in the fields of EPR and DNP.