Volume 12 Issue 3, March 2020

Many current methods to prepare 2-hydroxybiaryls require the prefunctionalization of phenol groups or show limited substrate scope. Now, use of a pentavalent sulfone-bridged bismacycle, formed in situ by telescoped boron-to-bismuth transmetallation and oxidation, allows the direct and regioselective ortho-arylation of unprotected phenols.

Although the application of force to induce chemical transformations is an active area of research, detailed understanding of these mechanochemical pathways is still lacking. Now, the mechanochemical activation of [4]-ladderane has been studied and found to exhibit unique non-equilibrium dynamic effects.

The structures of biologically active natural products have long served as inspiration in drug discovery. This Perspective outlines design principles and connectivity patterns for the de novo combination of natural product-derived fragments. The resulting ‘pseudo-natural products’ retain biological relevance yet exhibit structures and bioactivities not found in the natural products and their derivatives.

Does aromaticity have a size limit? Evidence is presented for global aromaticity in porphyrin nanorings with circuits of up to 162 π-electrons. The conformation of the nanoring can be altered by changing the template, which in turn controls the aromaticity. Whenever a ring current is observed, its direction is correctly predicted by Hückel’s rule.

A conjugated diradicaloid cage has been synthesized and its aromaticity was investigated. The neutral compound and the dication have dominant monocyclic conjugation pathways and both are aromatic (the former following Hückel’s rule and the latter Baird’s rule). The tetracation ([6n + 4] π-electrons) exhibits global 3D antiaromaticity whereas the hexacation ([6n + 2] π-electrons) exhibits global 3D aromaticity and has high D₃ symmetry.

Homooligomerization systems can be used to construct nanoarchitectures and to aid understanding of natural analogues. But the formation of such artificial systems with structural diversity and complexity comparable to that of biological systems is challenging. Now, an artificial branched kissing-loop motif has been designed, which links tiles folded from a single strand of RNA to give diverse homooligomeric nanostructures.

Step-economic access to the biologically relevant 2-hydroxybiaryl motif represents a long-standing challenge in synthetic organic chemistry. Now, a bismuth-mediated oxidative arylation of phenols and naphthols with boronic acids has been developed — supported by experimental mechanistic insight — giving a direct and practical route to this valuable molecular architecture.

Porous liquids promise to combine the advantages of the porosity of solids with those of the fluidity of liquids. Now, a permanently porous ionic-liquid coordination cage has been assembled that encapsulates isomers of butanol and propanol with some size and shape selectivity, as well as three gaseous chlorofluorocarbons with a size-dependent affinity.

The anti-Markovnikov hydroarylation of unactivated alkenes with unactivated arenes has been achieved with high selectivity by using nickel catalysts bearing large N-heterocyclic carbene ligands. Energy decomposition analysis indicates that the high activity of the catalysts with large carbene ligands arises from stabilizing non-covalent interactions rather than steric effects.

The deposition of noble metals onto two-dimensional transition metal dichalcogenides is crucial for practical applications, including in catalysis and sensing, yet this process has remained difficult to control. Now, gold and silver have been shown to grow on colloidal transition metal dichalcogenide nanosheets into either atomically thin layers or nanoparticles whose sizes and morphologies depend on the relative strengths of the interfacial noble metal–chalcogen bonds.

Although methods exist for the construction of CF₃-containing stereocentres, the utilization of α-trifluoromethyl carbanions remains challenging because of the propensity for fluoride elimination. A strategy has now been developed to stabilize these carbanions through a neighbouring cationic Pd complex and the corresponding Pd-stabilized zwitterions participate in asymmetric cycloadditions with a broad range of acceptors.

The mechanochemical activation of [4]-ladderane/ene has been studied and found to exhibit cascade unzipping and a consistent stereochemical distribution of products under various conditions and in different polymer backbones. Ab initio steered molecular dynamics simulations revealed unique non-equilibrium dynamic effects in the mechanochemistry of ladderane, cascade activation and reaction pathway bifurcation.

Although biaryl rings can be easily formed via cross coupling, their tetrahedral, high-fraction sp³ equivalents cannot. Now the scope, mechanism and biological profile of a general attached-ring synthesis has been probed. This provides direct access to full bridgehead substitution via sp³–sp³ coupling and enables rapid entry to natural product space.