Research articles

Atroposelective synthesis of C–N axially chiral anilides typically requires preformed aromatic ring systems. Now, a cobalt-catalysed atroposelective C–H activation and annulation method to construct isoquinolinones from benzamides, with C–N axially chirality, is reported. Using a chiral salicyl-oxazoline ligand and O₂ as an oxidant, the method yields isoquinolines in excellent yields and enantioselectivities.

The Mizoroki–Heck reaction forms C−C bonds between aryl halides and alkenes. For electron-deficient alkenes, β-coupled products are typically formed and synthesizing α-arylated products is challenging. Now, a triple catalysis system (nickel, photoredox catalysis and sulfinate) enables regioirregular formal Mizoroki–Heck reactions for electron-deficient alkenes and styrenes to give α-arylated alkenes.

Enantioselective C–H amination is an attractive strategy for the synthesis of chiral amines. Now, a combined radical and ionic approach has been developed for 1,2-difunctionalization of alcohols by merging enantioselective radical C–H amination with stereospecific nucleophilic ring-opening, enabling synthesis of β-functionalized chiral amines.

The high stability of THF and rapid cleavage of α-anionic THF make the direct generation and use of α-anionic THF challenging. Now, a flow synthetic method is used to control the metallation of unstable α-anionic THF, allowing a range of functionalization reactions to be carried out directly on THF.

Nature evolves diverse pathways for production of acetyl-CoA, a principal biosynthetic building block. Now, through in silico thermodynamic and kinetic analyses, this study proposes an acetyl-CoA biosynthetic route from C1 compounds and implements it in gas-fermenting bacteria for effective production of C2 metabolites.

Interlocking between non-trivial molecular knots provides a route to topologically complex mechanically interlocked molecules. Now, a topologically chiral prime link with 14 crossings is synthesized in a stereoselective manner through the quadruple interlocking of two homochiral trefoil knots.

Ketyl radicals can be used in a range of reactions, but their generation often requires harsh conditions and a large excess of reductants. Now, a multicomponent, palladium-photocatalysed reaction between aldehydes, 1,3-butadiene and N, S, O and C nucleophiles to build architecturally complex homoallylic alcohols is reported wherein ketyl-type radicals are generated under mild conditions.

The selective functionalization of C=C bonds of alkenes is well studied, however, regio- and enantioselective transformations of the allylic C–H bond of unactivated alkenes are relatively underexplored. Now, a palladium-catalysed branch-selective and enantioselective allylic C−H alkylation of α-alkenes is reported. The process tolerates a wide range of α-alkenes, from chemical feedstocks to bioactive α-alkenes

Methods for the hydrofluoroalkylation of alkenes often require expensive reagents and have limited reaction scope. Now, a photoinduced manganese-catalysed hydrofluoroalkylation is reported, providing an array of fluoroalkyl-containing products from fluoroalkyl halides. Mechanistic studies reveal that the bidentate phosphine ligand plays a key role in atom transfer processes and increases the stability and lifetime of the metalloradical intermediate.

Synthetic routes to aminoglycosides are often long and rely upon the coupling of semisynthetically produced fragments. Now, an enantioselective, copper-catalysed hydroamination of benzene has been developed to enable access to the aminoglycoside antibiotic ribostamycin. This bottom-up strategy provides modular and expedient entry into the aminocyclitol class.

Strategies for the creation of topological carbon nanostructures have greatly advanced synthetic organic chemistry and materials science. Now, the synthesis of a Möbius carbon nanobelt, a molecule with a twist on belt-shaped aromatic hydrocarbons, is reported.

Making many stereogenic centres in a single step remains a challenge. Now, a combined nickel and copper-catalysed stereodivergent propargylic substitution process has been developed to access four stereoisomers of amathaspiramide D. The scope of the reaction is shown across a range of propargylic carbonate and aldimine ester substrates to generate a number of chiral propargylated α-amino ester products.

Enantioselective dearomatization of substituted non-activated benzene derivatives is a challenge due to their inherent stability. Now, a chiral samarium complex-mediated enantioselective dearomatization of substituted benzene derivatives is realized via intramolecular reductive coupling with ketyl radicals. The method has been used to synthesize a range of dearomatized bicycles with three stereogenic centres.

Making highly crystalline covalent organic frameworks (COFs) is challenging and existing linkages used for constructing COFs are limited in terms of variety and functionality. Now, crystalline COFs with imidazopyridinium linkages, which serve as precursors to N-heterocyclic carbenes, have been synthesized, expanding the reactivity of COFs by incorporating chemical ambivalence (electrophilicity and nucleophilicity) into the linkages. The COFs are also used as cathode materials in lithium–sulfur batteries.

The synthesis of graphynes has often been limited to using irreversible coupling reactions that are likely to result in materials that lack long-range order. Now, a periodically sp–sp²-hybridized carbon allotrope, γ-graphyne, is prepared using a reversible dynamic alkyne metathesis and managing the balance between kinetic and thermodynamic control. This material’s interlayer stacking and folding behaviour are also revealed.

The coupling of sulfonimidoyl fluorides and alkynes using sulfur(VI) fluoride exchange (SuFEx) reactions has not been available because of the intrinsic reactivity of the π component. Now, a divergent SuFEx process between sulfonimidoyl fluorides and alkynes to produce vinylic or acetylenic sulfoximines is reported. Mechanistic studies reveal the origins of the vinylic sulfoximines, and several synthetic transformations of the products demonstrate the utility of the process.

Cross-coupling reactions between aryl halides and alcohols using copper are challenging due to the energetically demanding oxidative addition of copper into aryl halides. Now, this high-barrier step is bypassed using an energy transfer or direct excitation strategy for copper-mediated cross-coupling reactions. This process enables the use of aryl chlorides as electrophiles and alcohols, amines and fluoride as nucleophilic coupling partners.

In nature, terpenes are made by forming isoprene chains and then folding the chains into carbocycles, followed by oxidation and rearrangement reactions. Now, inspired by nature, a range of polycyclic terpene structures are synthesized from phenols through a three-step sequence of prenylation, dearomatization and/or prenyl migration, and then epoxidation and/or radical cyclization. Several total syntheses of natural products are carried out using this approach.

The synthesis of all possible stereoisomers of drug candidates is essential for pharmaceutical development. However, only a few catalytic enantioselective methods provide access to all stereoisomers of molecules with contiguous stereocentres. Now, a strategy combining nickel and squaramide catalysis enables the stereodivergent α-propargylation of oxindoles and subsequently the synthesis of three natural products.

The [2+2+2] cyclotrimerization of two distinct alkynes and alkenes to form six-membered carbocycles is typically constrained by competing β-hydride elimination, low stereocontrol and the need to add reagents slowly. Now, a rhodium-catalysed three-component [2+2+2] cyclotrimerization with excellent chemo-, regio- and stereocontrol is reported that does not require any special operations. The utility of the process is shown and mechanistic studies probe the origins of the selectivity.