Iterative Synthesis Strategies for Boron-Containing Compounds

Iterative synthesis strategies for boron-containing compounds have emerged as powerful tools for the modular construction of complex molecular architectures. Central to these approaches is the use of boron reagents—often boronic acids, esters or masked boronates—to enable sequential bond-forming events under finely controlled conditions. Masking groups such as MIDA (N-methyliminodiacetic acid) facilitate the temporary protection and unmasking of boron centres, allowing each coupling step to proceed with high selectivity and orthogonality. Dynamic covalent methods, notably reversible B–O bond formation in boroxine frameworks, extend this paradigm by permitting error-correcting assemblies under aqueous or mildly acidic conditions. Together, these tactics support the rapid generation of diverse scaffolds—from polyenes and heterocycles to functional materials—through systematic, iterative manipulations of C–B and B–O linkages. The global significance of these platforms is evident in applications ranging from drug discovery, where precise stereochemical control and late-stage diversification are paramount, to materials science, where dynamic networks and self-healing polymers rely on reversible boron-based bonds.

Research from Nature Portfolio

Recent studies have demonstrated a water-compatible dynamic covalent bond based on a boroxine structure formed from 2-hydroxyphenylboronic acid dimers. This reversible dehydration under mildly aqueous conditions overcomes traditional limitations of boroxines and opens avenues for constructing dynamic networks and adaptable molecular assemblies in biological or hydrophilic environments.

Another key development involves a palladium-catalysed syn-diarylation of arylethynyl MIDA boronates to yield triarylalkenyl MIDA boronates with exceptional regio- and stereocontrol. The masked B(MIDA) group confers both stability and orthogonal reactivity, enabling subsequent Suzuki–Miyaura coupling or base-promoted protodeborylation in an iterative manner. This step-economic, modular approach allows the rapid assembly of tetra- and triarylethenes with diverse substitution patterns and precise geometrical control.

Iterative Synthesis Strategies for Boron-Containing Compounds publication trend

The graph below shows the total number of articles in iterative synthesis strategies for boron-containing compounds across all publications each year (not limited to Nature Index journals).

Technical terms

Iterative cross-coupling: A sequential bonding process in which a boron reagent alternates between masked and unmasked states to form multiple C–C bonds with high regio- and stereocontrol.

MIDA boronate: A boron species masked by N-methyliminodiacetic acid, which stabilises the boron centre and allows temporal control over reactivity in iterative syntheses.

Boroxine: A cyclic trimer formed by dehydration of boronic acids, capable of reversible B–O bonds used in dynamic covalent assemblies.

Speciation: The distribution of different chemical forms of a boron reagent in solution, which can be manipulated to achieve selective reactions.

Protodeborylation: A reaction in which a boron–carbon bond is replaced by a hydrogen atom, often used as a termination step in iterative coupling sequences.

Dynamic covalent bond: A reversible covalent linkage that can break and reform under equilibrium control, enabling self-healing or adaptive materials.

References

1. Water-compatible dynamic covalent bonds based on a boroxine structure. Communications Chemistry (2024).
2. Regio- and stereoselective synthesis of tetra- and triarylethenes by N-methylimidodiacetyl boron-directed palladium-catalysed three-component coupling. Communications Chemistry (2019).
3. Reactivity of 1,3-enyne MIDA boronates: exploration of novel 1,2-alkyne shift via gem -difluorination. Chemical Science (2024).
4. Sequential and iterative Pd-catalyzed cross-coupling reactions in organic synthesis. Monatshefte für Chemie - Chemical Monthly (2016).
5. Chemoselective Boronic Ester Synthesis by Controlled Speciation. Angewandte Chemie International Edition (2014).
6. A Simple and General Platform for Generating Stereochemically Complex Polyene Frameworks by Iterative Cross‐Coupling. Angewandte Chemie International Edition (2010).