Only water: Phenols have been shown to undergo a ruthenium-catalyzed ortho-alkylation reaction (see scheme; Cy=cyclohexyl). Unactivated alcohols are used as the alkylating agents and water is the only by-product that is generated, making this transformation more atom-economical and greener than traditional methods.

Getting real: Although 1-azidoalkenes are known as important intermediates for the formation of many nitrogen heterocycles, for a long time the existence of the corresponding 1-azidoalkynes could not be proven unequivocally. The recent synthesis and full characterization of 1-azidoethyne have provided incontrovertible verification of this substance class.

G protein-coupled receptors with seven transmembrane helices (see picture) are the most important drug targets in medicine. Their molecular and structural characterization has now been honored with the Nobel Prize for Chemistry to Robert J. Lefkowitz and Brian K. Kobilka.

A one-off: Single-cell analysis is one of the most interesting applications for droplet microfluidics. Droplets provide robust compartments on the size scale of a single cell, and their ability to encapsulate and rapidly manipulate cells along with their immediate environment in monodisperse compartments allows the possibility of automation. This Review focuses on single-cell analyses and applications in drug screening and genetic and enzyme analysis.

Stack it up: Reduction of corannulene with an excess of lithium metal in dimethoxyethane (DME) results in the formation of remarkable multilayered supramolecular aggregates (see picture) having lithium alkoxo nanobelts encapsulated between two tetrareduced corannulene bowls, [C₂₀H₁₀⁴⁻/Li₆(OR)₆Li₆/C₂₀H₁₀⁴⁻]²⁻. The alkoxo groups (R=CH₃O or/and CH₃OCH₂CH₂O) are products of the Li-induced DME cleavage.

Silver in a gold mine: A triple-decker Au^I–Ag^I ion cluster was synthesized by alternate alignment of cyclic trinuclear Au^I complexes and Ag^I ions within a self-assembled cage. The box-shaped cavity of the cage is suitable not only for limiting the cluster number, but also for the stabilization of weakly associated metal ions, which cannot exist without the help of the cage.

Carbon nanofibers were synthesized from common solid carbon sources (such as artificial graphites and acetylene black) in the presence of an iron catalyst by direct carbonization. This inexpensive and simple method is expected to trigger a revolution in the preparation of nanocarbons.

BBC news: Two boron atoms have been incorporated into a carbon nanosheet by a bottom-up synthesis to give a “B-doped nanographene” (see picture) with a defined structure. The experimental and theoretical analyses revealed the important role of the two boron atoms in producing its characteristic properties, such as broad absorption bands covering the visible region and reversible redox processes.

The coupling of HSiEt₃ and related silanes to β-diiminate ligands is achieved through a series of SiH, CH, and SiC bond-breaking and bond-forming reactions. Complex 1 (see scheme) loses an Et(Si) group as ethane and couples the remaining SiEt₂H fragment to a benzylic methyl group of the ligand skeleton. According to DFT calculations, the reaction involves silylene intermediates.

C-dots on hand: Luminescent carbon nanodots were synthesized and were shown to be biocompatible, have low toxicity, and distinctive photoluminescence properties. These C-dots are inexpensive to synthesize and could potentially be used for versatile applications, such as anticounterfeiting, information encryption, and information storage.

Under two conditions: Hydroamination catalyzed by group 4 metals is featured in the modular and enantioselective synthesis of 3-substituted morpholines and the diastereoselective synthesis of 2,5-substituted piperazines.

Don′t sweat it: “Negative” fingermarks are developed on paper by the application of gold nanoparticles (gold circles) that are capped by a bifunctional ligand, and then silver precipitation. In this process, paper is the substrate and the fingermarks serve as a mask. This approach may contribute to the successful recovery of latent fingermarks by law enforcement agencies.

A molecular-scale gap array is introduced into a single-layer graphene sheet by a lithographic dash-line cutting process. Electrically active molecules are then covalently wired into these point contacts in high yield, thus forming stable molecular devices that for example are able to reversibly switch their conductance by chemical treatment.

Please release me: Electrochemically activated cell release is achieved using a redox-active supramolecular complex (see picture). Host molecule CB[8] (green) links surface-bound viologen (purple) with solution-exposed RGD peptides (red). Electrochemical reduction dissociates the complex, releases the peptides, and thus releases the cells from the substrates. This supramolecular strategy is also applicable to microelectrodes.

Turning a new leaf: The first structures isolated from Thuiaria breitfussi, the breitfussins, are presented. This structural class consists of indole–oxazole–pyrrole units. Limited quantities prevented crystallization; therefore, the structures were solved using a novel combination of AFM, computer-aided structure elucidation (CASE), and DFT calculations. Visualization by AFM determined all the connection points of the cyclic systems and the other substituents.

Well-balanced: ¹⁹F NMR spectroscopy defined a trifluoromagnesate complex for protein kinase A (multicolored) with adenosine diphosphate (black), the MgF₃⁻ ion (green), and the SP20 peptide substrate (purple with dots). A sphere (cyan) centered on the MgF₃⁻ ion embraces all catalytic components and much of the SP20 substrate. The content of the sphere is uncharged conforming to the charge balance hypothesis.

An important regulator of innate immunity, the protein complex of Toll-like receptors 1 and 2 (TLR1/TLR2) provides an attractive target for the treatment of various immune disorders. The novel compound CU-CPT22 can compete with the binding of the specific lipoprotein ligand to TLR1/TLR2 (see picture) with high inhibitory activity and specificity. Repression of downstream signaling from TNF-α and IL-1β was also observed.

Ride the (micro)wave: The title strategy has been developed for the synthesis of various symmetric or unsymmetric hydroxylated stilbenoids utilizing 4-halophenols and acrylic acid as coupling partners (see scheme; DMA=N,N-dimethylacetamide, MW=microwave). Protecting groups are not necessary and a single palladium catalyst is used.

The automated sequence-controlled copolymerization of styrene and N-substituted maleimides allowed the production of unprecedented polymer microstructures (up to 65536 possible microstructural arrangements). Highly complex monomer sequence patterns were prepared using four N-substituted maleimides (see picture).

No trafficking: The antitumor-active trans-platinum/thiazole complex trans-PtTz demonstrated high reactivity to the transcription factor Sp1, which is overexpressed in tumor cells. The binding of trans-PtTz disrupts the DNA interaction with Sp1 in vitro and prevents the protein trafficking from the cytoplasm into the nucleus (see picture).

The convergent synthesis of human parathyroid hormone-related protein (hPTHrP, see scheme) has been accomplished through iterative peptide ligations followed by global metal-free dethiylation. The biological activity of synthetic PTHrP has been demonstrated.

To mix or not to mix: Integrated (left) and segregated (right) assemblies were obtained upon treating functionalized γ-Fe₂O₃ nanoparticles (NPs) with AuNPs. Their binary nature is controlled by the capping layer of the γ-Fe₂O₃ NPs and the AuNP initial aggregation state. The segregated assembly formation is induced by AuNP aggregates which act as nucleation sites for growth of the γ-Fe₂O₃ NP domains.

Don′t touch! Aptamers selected against lysozyme are transformed into aptamer-based reagents, with which latent fingermarks can be developed with high selectivity and sensitivity. The design of aptamers targeting components of latent fingermarks opens up a new range of detection methods that previously have not been explored.

How to lose fluorine: Biologically relevant oxazolidinones 1 were synthesized through the desymmetrization of unactivated aliphatic difluorides by Si-induced catalytic CF bond-cleavage using BSA/CsF (BSA=bis(trimethylsilyl)acetamide). The direct transformation of 2 with isocyanates into 1 by cascade carbamoylation/cyclization, in which cyclization is induced by Na-assisted CF bond activation, was also achieved.

Siloxides can support U! …︁in the reduction of small molecules with uranium complexes. The treatment of [U{N(SiMe₃)₂}₃] with HOSi(OtBu)₃ (3 equiv) yielded a novel homoleptic uranium(III) siloxide complex 1, which acted as a two-electron reducing agent toward CS₂ and CO₂ (see scheme). Complex 1 also reduced toluene to afford a diuranium inverted-sandwich complex.

Rare sugars by CH activation: The title compounds have been prepared from the corresponding 6-deoxysugars by an intramolecular CH activation in high yields. Diethyl silane is attached to the 4-OH group followed by formation of a SiC bond; both transformations are catalyzed by iridium in a one-pot fashion. The subsequent Fleming–Tamao oxidation provided the L-sugars.

Three-component coupling, with a pair: The combination of Cu^II and Ti^IV catalyzes the first three-component coupling of unactivated ketones with a diverse range of amines and terminal alkynes. Tetrasubstituted propargylamines are formed under green, solvent-free conditions (see scheme). This dual metal system overcomes the barrier to ketimine formation and subsequent attack, opening a new path to multicomponent reactions of ketone electrophiles.

Rings, rings, rings: A Friedel–Crafts intramolecular arylation for the synthesis of polycyclic aromatic hydrocarbons from aryl triazenes has been achieved. Polycyclic aromatic compounds consisting of five-, six-, and seven-membered rings can be prepared using this method.

A small change with a big effect: Reaction of the titanium complex 1 with terminal alkynes gave the unusual acetylide–vinylhydrazide(1−) compounds 2 (R=4-C₆H₄X (X=Me, CF₃, OMe), C₆F₅, SiMe₃) as hydrohydrazination intermediates. In contrast, a complex similar to 1 with bulkier trimethylsilyl substituents in place of the isopropyl groups is known to catalyze the 1,2-diamination of alkynes with hydrazines.

A photo opportunity: A visible-light-excited iridium catalyst delivers electrons from an amine to an organohalide. The electron transfer then induces reductive scission of the carbon–halogen bond, generating the corresponding alkyl, alkenyl, and aryl radical that can undergo cyclization and hydrodehalogenation reactions.

Externally yours: 2,3-Dihydroquinolin-4(1H)-ones are obtained in moderate to good yields (40–84 %, see scheme) in a metal-free oxidation/C(sp³)H functionalization of unactivated aryl alkynes. 2,6-Dichloropyridine-N-oxide is used as an external oxidant. In the reaction, a Brønsted acid, not a metal, plays a key role in the triple CC bond activation.

Two nucleophiles, one triple bond: Under aerobic conditions, palladium-catalyzed direct coupling of o-alkynylanilines and terminal alkynes took place smoothly to afford the 2,3-disubstituted 3-alkynylindoles 3 in good to excellent yields. The intermediate A was characterized and a retro-aminopalladation of B was observed for the first time.

Ring the changes: Enyne acetals were easily converted into hydroazulene skeletons by a new and efficient metal-free route involving a Brønsted acid promoted carbocyclization and a subsequent stereospecific Nazarov cyclization (see scheme). The versatility of this transformation also allowed assembly of interesting heteroaromatic tricyclic systems.

The Sonogashira cross-coupling polymerization of a dibrominated cyclopenta[hi]aceanthrylene and a diethynylfluorene derivative produced a donor–acceptor copolymer composed solely of cyclopenta-fused polycyclic aromatic hydrocarbons. The resulting polymer displays low band gaps (<1.5 eV), dual absorption bands, and electron-accepting behavior as demonstrated through fluorescence quenching of poly(3-hexylthiophene).

Tiny reactors: By using a surfactant (see picture), domains of poly(ethylene glycol) (PEG) at the nanometer scale are dispersed within reverse micelles formed in supercritical CO₂. The size and properties of the PEG domains are tuneable by changing the PEG content. Furthermore, the PEG domains have been used as nanoreactors to synthesize highly dispersed gold nanocrystals.

An efficient enantioselective approach to form trans lactams and cis lactones in up to 98 % yield with greater than 99 % ee, and greater than 20:1 d.r. using simple aliphatic aldehydes has been developed. The process involves a new pathway to generate enolate intermediates from aliphatic aldehydes by oxidation and deprotonation. NHC=N-heterocyclic carbene, Ts=4-toluenesulfonyl.

Swapped: Commercially available quinolinone derivatives (1 or 2, see scheme) were reacted with arylboronic acids in the presence of a Rh^I complex to give aryl(quinolin-8-yl)methanone products 3 in medium to good yields. A mechanism that involves the in situ oxidation of Rh^I to Rh^III by O₂ in the presence of CuI was proposed.

Mod squad: Multiple small molecules appear to spontaneously self-assemble to form supramolecular amine catalysts that have high reactivity, good efficiency, and enhanced turnover numbers. These modular organocatalysts should be applicable to many iminium as well as hydrogen-bond catalytic reactions and provide new insights into asymmetric catalysis.

General solution: An efficient rhodium-catalyzed dual CH bond activation and cyclization of N-methoxybenzamides 1 with aryl boronic acids 2 (see scheme; Cp*=Me₅C₅) provides a straightforward and general approach to the phenanthridinone structure, which occurs widely in natural products and drugs. Highly regioselective CC and CN bond formation under mild conditions afforded a wide range of substituted phenanthridinones 3.

Olefinic CH activation of N-allyl sulfonamides in the presence of [{RhCp*Cl₂}₂] (Cp*=Me₅C₅) enabled their oxidative coupling with alkynes to generate 1,2-dihydropyridines, pyridines, and cyclopentenones (see scheme; Ts=p-toluenesulfonyl). The type of highly substituted product formed was controlled by the substitution of the allyl group and the reaction conditions.

Done with 'F'lair: Enantioselective fluorination was achieved by Rh^I-catalyzed ring opening of oxabicyclic alkenes using Et₃N⋅3 HF. The chiral fluorinated scaffolds were obtained under mild reaction conditions in standard glass vessels, and served as useful building blocks for various chiral fluorinated targets. cod=cycloocta-1,5-diene, ppf=phenylphosphinoferrocene, THF=tetrahydrofuran.

And palladium makes three: In contrast to the formation of cyclic dimers in the Cu-mediated reaction, Pd-catalyzed oxidative coupling of 2,18-diethynylporphyrins preferentially produced cyclic trimers (see scheme). A porphyrin hexamer with a doubly 1,3-butadiyne-bridged conjugated trimeric core and directly meso-appended peripheral porphyrin substituents was also synthesized.

Radicals and anions: The TEMPO-mediated oxidation of magnesiated iodoarenes A provides highly regioregular poly(m-phenylenes) by strictly alternating anionic/radical cross-over chain-growth polymerization. Poly(m-phenylenes) with mean molecular weight (M_n) of up to 20 000 g mol⁻¹ can be prepared under mild conditions by this method. The approach is a new concept for transition-metal-free polyarene synthesis. TEMPO=2,2,6,6-tetramethylpiperidine-N-oxyl radical.

The poorer, the better: A metal-free catalytic procedure for the reduction of electron-poor allenes and alkenes has been developed. The method employs a frustrated Lewis pair based catalyst. 1,4-Diazabicyclo[2.2.2]octane (DABCO)/B(C₆F₅)₃ was shown to be the best combination in optimization studies.

54 years later: Saturated imidazolidin-2-ylidenes react with aldehydes to smoothly produce the elusive 2,2-diamino enols A (“Breslow intermediates”, first postulated in 1958) of carbene-catalyzed umpolung reactions. The 2,2-diamino enols A react with additional aldehyde in a cross-benzoin reaction. The methylated Breslow intermediates B are accessible by deprotonation of methoxymethyl azolium salts.