Borylation Strategies in Organic Synthesis

Borylation encompasses a suite of methodologies for installing carbon–boron bonds, a transformation that has revolutionised the synthesis of organoboron reagents used in cross-coupling, pharmaceutical lead generation and advanced materials. Traditional approaches rely on transition-metal catalysis—most notably palladium, copper and nickel systems—to activate aryl and alkyl halides, carboxylic acid derivatives or C–H bonds for subsequent borylation. In recent years, photochemical and radical-mediated tactics have expanded the substrate scope to include unactivated C–X and C–H bonds under mild, reagent-economical conditions. Decarboxylative and deoxygenative variants enable direct conversion of abundant feedstocks such as carboxylic acids into boronate esters, while base-promoted and electron-donor–acceptor-complex strategies allow metal-free C–B bond formation with high selectivity. Collectively, these advances have enhanced functional-group tolerance, streamlined late-stage functionalisation of complex molecules and opened new avenues for the synthesis of polyboron architectures and fluorinated building blocks.

Research from Nature Portfolio

Visible-light-driven gold catalysis has been harnessed for divergent radical dechloroborylation of gem-dichloroalkanes, delivering alkyl boronic esters, α-chloroboronic esters and gem-diboronates in yields of up to 92 per cent. The inner-sphere electron-transfer mechanism surmounts the high redox potential of unreactive alkyl chlorides and permits late-stage modification of bioactive scaffolds on preparative scale.

A direct photocatalytic decarboxylative borylation protocol transforms free carboxylic acids into boronate esters under visible-light irradiation without requiring pre-functionalised redox-active esters or stoichiometric additives. This mild, operationally simple method generates CO₂ as the sole by-product and exhibits broad compatibility with sensitive functional groups, guided by a biomimetic guanidine-based activation mechanism.

A complementary metal-free deoxygenative borylation has been realised using a strongly reducing diboron reagent, enabling C–O bond cleavage of aromatic and aliphatic carboxylic acids to furnish benzylboronates and 1,1,2-alkyl(trisboronates). Detailed mechanistic studies reveal a stepwise C–O activation pathway that may inform future reductive functionalisation strategies of oxygenated feedstocks.

Borylation Strategies in Organic Synthesis publication trend

The graph below shows the total number of articles in borylation strategies in organic synthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Borylation: Introduction of a carbon–boron bond into an organic molecule, foundational for organoboron reagent synthesis.

Boronate ester: A compound bearing B–O bonds, commonly used as a stable precursor in cross-coupling reactions.

Decarboxylative borylation: Transformation in which a carboxyl group is removed as CO₂ to form a new C–B bond.

Deoxygenative borylation: Conversion of a C–O bond (typically from alcohols or carboxylic acids) into a C–B bond by removal of oxygen functionality.

Electron-donor–acceptor (EDA) complex: A non-covalent assembly of electron-rich and electron-poor species that undergoes bond activation upon light absorption.

Radical borylation: C–B bond formation via radical intermediates, often initiated by photochemical, base-mediated or redox processes.

References

1. Dinuclear gold-catalyzed divergent dechlorinative radical borylation of gem-dichloroalkanes. Nature Communications (2024).
2. Photocatalytic direct borylation of carboxylic acids. Nature Communications (2022).
3. Direct deoxygenative borylation of carboxylic acids. Nature Communications (2021).
4. Photoinduced Site-Selective Aryl C-H Borylation with Electron-Donor-Acceptor Complex Derived from B2Pin2 and Isoquinoline. Molecules (2024).
5. Base‐Mediated Radical Borylation of Alkyl Sulfones. Chemistry - A European Journal (2021).
6. Efficient metal-free photochemical borylation of aryl halides under batch and continuous-flow conditions. Chemical Science (2016).