Computation-Driven Experimental Discovery of Reactivity Space of Organoboron Compounds

ConspectusOrganoboron compounds serve as fundamental building blocks in the construction of diverse functional molecules, ranging from pharmaceuticals to materials. The discovery of boron-related new chemical transformations serves as a pivotal driving force for developing functional substances. Nevertheless, de novo design of new reactions remains challenging, requiring both the elucidation of complex competing pathways at the molecular level and efficient navigation of high-dimensional parameter spaces of reaction conditions. Consequently, the emergence of new reaction modes still largely relies on serendipity, and progress remains slow. Recent advances in theoretical methods, computational software, and artificial intelligence have created unprecedented opportunities to accelerate new reaction discovery. This overview builds upon decades of organoboron research to demonstrate how the integration of computational and experimental studies has elucidated exceptional reactivities through precise coordination engineering, thereby establishing new, transition-metal-free synthetic methodologies based on these activation modes. Key contributions include novel activation modes for commonly used organoboron reagents such as B₂pin₂ and benzylic boronates, alongside unique mechanistic scenarios in B(C₆F₅)₃ catalysis.In this Account, we begin by discussing the counterintuitive mechanisms in B(C₆F₅)₃-catalyzed ortho-functionalization of phenols with unsaturated hydrocarbons. Our computational studies showed that the pathway does not involve a conventional Lewis acid-alkene complex. Instead, coordination of B(C₆F₅)₃ to phenols significantly enhances the Brønsted acidity of phenolic hydroxyl groups. This enables the protonation of alkenes or alkynes and facilitates a range of reactions of ortho-functionalization to produce allylated, alkenylated, propargylic alkylated, and alkylated phenols.While diboron(4) compounds are staples in synthetic chemistry, their activation has traditionally relied on transition metals or strong bases, the latter typically leading to heterolytic B-B bond cleavage. In 2016, our comprehensive computational screening revealed that dual coordination of the boron atoms in B₂pin₂ by two 4-cyanopyridine molecules promotes facile homolysis, yielding pyridine-ligated boryl radicals. Further experiments confirmed the formation of resonance-stabilized radical species, while computational studies further illustrated that the related radicals can serve either as a boryl radical precursor for radical addition or as a pyridine radical for C-C coupling reactions. Such an activation mode has inspired the development of diverse radical cross-coupling reactions and gained broad adoption in boryl radical chemistry.Furthermore, we demonstrate that a computational and data-driven strategy elucidates the heterolytic cleavage of C-B bonds. By tailoring the substituents around the ate complex formed between simple boronates and alkali metal alkoxides, this activation mode generates reactive organopotassium species. Such unique reactivity unlocks diverse organometallic-type processes, including dehalogenative metalation, C-H deprotonation, and alkene addition, thereby significantly expanding the synthetic utility of these boronates beyond their conventional role as coupling partners in C-C bond formation.Perspective is given in the direction of computationally exploring uncharted chemical space to uncover exceptional reactivities in organoboron compounds. This Account is expected to offer a paradigm for advancing synthetic methodologies and efficient computational tools for a broad family of researchers.