A promising dual catalytic "Isothiourea + X" platform: from classic ionic to radical transformations

In recent decades, significant advancements have been made in isothiourea (ITU) catalysis, particularly in acyl transfer, silyl transfer, annulations, additions via C(1)-ammonium enolates and [2,3]-sigmatropic rearrangements. Despite these achievements, challenges such as a limited substrate scope of substrates and restricted reaction patterns still remain prevalent. The development of dual catalytic strategies involving secondary catalysts such as electricity, light, transition metals, and Brønsted acids has addressed these issues. This review focuses on the "Isothiourea + X" dual catalytic approach, highlighting recent breakthroughs that extend isothiourea catalysis from classic ionic reactions to radical transformations. Notable advances include the use of ITU-activated ammonium intermediates in asymmetric radical additions, as well as the light-driven generation of ketimine intermediates catalyzed by ITU. Furthermore, the integration of ITU with transition-metal catalysis has expanded its application, enabling reactions with a variety of in situ generated intermediates and promoting chiral cyclization. The review also examines the synergistic effects of ITU in combination with Brønsted acids, which enhance both reaction efficiency and stereocontrol. By summarizing these developments, the review provides valuable insights and directions for future research in ITU catalysis, particularly in the context of green, efficient, and asymmetric radical transformations across multiple fields.