Search

N-Glycosylated heterocycles play important roles in biological systems and drug development, but the synthesis heavily relies on ionic N-glycosylation. Herein, the authors report a dehydroxylative radical method for synthesizing N-glycosides by leveraging copper metallaphotoredox catalysis.

Phenols and their derivatives are ubiquitous in nature and important within the chemical industry. Their properties are linked to their substitution patterns, but meta-isomers are underrepresented due to the difficulty of their synthesis. Now we address this challenge by describing a 1,2-transposition of phenols that enables a formal para- to meta-isomerization.

Exploitation of noncovalent interactions has received much attention for the design of metal catalysts. However, because of the weak nature, CH-π interactions have been less utilized for the control of organic reactions. Here, the authors report that the CH-π interaction can be used to kinetically accelerate catalytic C-H activation of arenes.

Enantioconvergent reactions convert both enantiomers of a racemic starting material into a single enantioenriched product. All currently known enantioconvergent processes necessitate the loss or partial loss of the racemic substrate’s stereochemical information. Now, an alternative approach has been developed that proceeds with full retention of the racemic substrate’s configuration.

Chiral 1,2-benzazaborines are promising isosteres of naphthalene, but rarely explored due to the lack of efficient synthetic methods. Now, the copper-catalysed enantioselective hydroboration of alkenes with 1,2-benzazaborines has been developed, providing a general platform for the atom-economic and efficient construction of diverse chiral 1,2-benzazaborine compounds bearing a 2-carbon-stereogenic centre or allene skeleton.

Developing facile and direct synthesis routes for enantioselective construction of cyclic π-conjugated molecules is crucial but the chirality orginiating from the distorted structure around heptagon-containing polyarenes is largely overlooked. Herein the authors present a highly enantioselective synthesis for fabrication of all carbon heptagon-containing polyarenes via palladium-catalyzed carbene-based cross–coupling of benzyl bromides and N-arylsulfonylhydrazones.

The synthesis of sequence-regulated oligosulfates has not yet been established due to the difficulties in precise reactivity control. Here, the authors report a multi-directional divergent iterative method to furnish oligosulfates based on a chain homologation approach, in which the fluorosulfate unit is regenerated.

α-Amino acids possessing β-stereocentres are difficult to synthesize. Now, an iridium-catalysed protocol allows the direct upconversion of simple alkenes and glycine derivatives to give β-substituted α-amino acids with exceptional levels of regio- and stereocontrol. The reaction design is based on exploiting the native directing ability of a glycine-derived N–H unit to facilitate enolization of the adjacent carbonyl.

Planar chiral [2.2]paracyclophanes have a wide range of applications in asymmetric synthesis and materials science. However, they are accessed via time-consuming chiral separations or kinetic resolution approaches. Here, the authors report a simple, metal-free protocol for organocatalytic desymmetrization of prochiral diformyl[2.2]paracyclophanes.

Phenols and anilines are of extreme importance for medicinal chemistry and material science but the selective preparation of meta-substituted phenols and anilines remains challenging. Here the authors report an efficient copper-catalyzed dehydrogenation strategy to exclusively synthesize meta-carbonyl phenols and anilines from carbonyl substituted cyclohexanes.

Cross-dehydrogenative coupling (CDC) of C-H bonds is an ideal approach for C-C bond construction but suffers from low selectivity of similar C-H bonds. Here, the authors describe a highly selective paired electrocatalysis strategy towards CDC combining hydrogen evolution reaction catalysis with hydride transfer catalysis.

Umpolung reactions typically focus on carbonyls or imine derivatives. Here, the authors report the umpolung reaction of C–C σ-bonds in bicyclo[1.1.0]butanes (BCBs) with electrophilic alkenes, yielding various cyclobutenes or conjugated dienes.

O-Sulfation is a vital post-translational modification in bioactive molecules, yet there are significant challenges for the synthesis. Here, the authors report a general and robust approach to O-sulfation by harnessing the tunable reactivity of dimethyl sulfate or diisopropyl sulfate under tetrabutylammonium bisulfate activation.

Prostaglandins are of interest to synthetic chemists due to their biological activities. Here, the authors present a concise chemoenzymatic synthesis method for several representative prostaglandins, achieved in 5 to 7 steps, via the common intermediate bromohydrin, a radical equivalent of Corey lactone.

Planar-chiral cyclophanes are important for drug discovery but the enantioselective synthesis of planar-chiral cyclophanes remains challenging. Here the authors describe an N-heterocyclic carbene-catalyzed asymmetric construction of planar-chiral cyclophanes.

Chemical reduction of alkali cations to their metals is extremely challenging. Here, the authors synthesized a series of redox-active borate anions stabilized by bipyridine ligands which can reduce lithium ions generating elemental lithium metal and borate radicals.

Medium-sized-ring compounds are challenging synthetic targets in organic chemistry. Here the authors report an intramolecular dearomative [5 + 4] cycloaddition of naphthalene-derived vinylcyclopropanes to construct these molecules under visible-light irradiation and a proper triplet photosensitizer.

Stoichiometric amounts of metal reductant and the requirement of a directing group limit the application of transition metal-catalyzed reductive difunctionalization of alkenes with alkyl halides. Here, the authors report a reductive difunctionalization of alkenes via a radical-anion relay with Na₂S₂O₄ as both reductant and sulfone-source.

A couple-close approach used to build semisaturated ring systems from dual radical precursors allows sampling of regions of underexplored chemical space, leading to an annulation that can be used for late-stage functionalization of pharmaceutical scaffolds.

Unstrained aryl–aryl bonds are among the most inert bonds in organic chemistry. Now the development of a split cross-coupling strategy enables the direct functionalization of such bonds through Rh-catalysed C–C cleavage and cross-coupling with aryl halides, providing a method for biaryl synthesis.

Despite the widespread utility of ruthenium catalysts, many protocols for their use require high temperatures or light irradiation. Now, the synthesis of an air- and moisture-stable ruthenium precatalyst has been reported. This versatile catalyst drives an array of transformations and enables rapid screening and optimization of reactions, revealing previously unknown in situ generated ruthenium complexes.

We introduce a method for the direct 1,3-difunctionalization of alkenes, based on a concept termed ‘charge relocation’, which enables stereodivergent access to 1,3-difunctionalized products of either syn- or anti-configuration from unactivated alkenes.

Nature generates the stereoisomeric yohimbine alkaloids using bioavailable monoterpene secolaganin as the building block. Here, the authors reset the stage by the development of a bioinspired coupling, in which the pentacyclic skeleton is constructed through enantioselective kinetic resolution of an achiral, easily accessible synthetic surrogate.

The photochemical properties of Electron Donor-Acceptor (EDA) complexes present exciting opportunities, but often require an inert atmosphere to maintain high efficiency. Here, the authors develop a photocatalytic system through rational design, which overcomes the oxygen-sensitive limitation of traditional EDA photocatalytic systems.

Despite their intriguing photochemical activities, natural photoenzymes have not yet been repurposed for new-to-nature activities. Now, by leveraging the strongly oxidizing excited-state flavoquinone cofactor, fatty acid photodecarboxylases were engineered to catalyse unnatural decarboxylative radical cyclization with excellent chemo-, enantio- and diastereoselectivities.

While the homo N-N coupling of two NH moieties to form the hydrazide N-N bond is well developed, the crossdehydrogenative hetero N-N coupling remains unevolved. Here the authors present an efficient, PhI(OAc)2-mediated intermolecular N-N cross-coupling of primary benzamides with primary and secondary amines.

The oxidative intermolecular amination of C-H bonds represents a straightforward method to construct aliphatic allylic amines. However, the utilization of widely available internal alkenes remains a synthetic challenge. Here, the authors present a regioselective Cu-catalyzed oxidative allylic C-H amination of internal olefins with azodiformates.

Hydroxylamine plays a critical role in the chemical industry, but its production currently has unfavourable environmental footprint. Now a plasma-electrochemical cascade pathway powered by electricity enables efficient hydroxylamine synthesis from ambient air and water at mild conditions.

Aminated heteroaromatics are usually synthesized from heteroaromatic substrates. Now, a general photochemical approach that exploits non-aromatic N-heterocyclic ketones as starting materials for the coupling with amines under desaturative catalysis is reported as an alternative.

The development of divergent reaction pathways controlled by different ligands is a critical goal. Here the authors describe a cobalt-catalyzed strategy for cascade coupling of 1,3-enynes with two molecules of acrylates through three reaction modes.

Vitamin B3 derivatives display a range of biological activities. Here, the authors report the synthesis of meta-aminoaryl nicotinates, derivatives of vitamin B3, and their late-stage conjugation with (hetero)arylamines, ultimately expanding the chemical space for biomedical research.

Carbon isotope labelling of bioactive molecules is essential for accessing the pharmacokinetic and pharmacodynamic properties of new drug entities. Here, the authors propose an electrochemical isotope-labelling protocol which enables the use of near-stoichiometric ¹⁴CO₂, facilitating late-stage and single-step carbon-14 labelling of pharmaceuticals and representative precursors.

The selective synthesis of ultrahigh-molar-mass (UHMM) cyclic polymers from direct polymerization is elusive. Using a chemically recyclable polythioester as a model, it has now been shown that a common superbase mediates living linear-chain growth, followed by proton-triggered linear-to-cyclic topological transformation, producing UHMM cyclic polymers with a narrow dispersity.

We use bimolecular homolytic substitution catalysis to sort an electrophilic radical and a nucleophilic radical across an unactivated alkene, accelerating access to pharmaceutically relevant C(sp³)-rich molecules and defining a mechanistic approach for alkene dialkylation.

Enantioenriched α-disubstituted α-ethynylamines are valuable synthons to chiral α-tertiary amines and azacycles, but their facile access remains challenging. Now, sterically confined pyridinebisoxazoline ligands have been developed to facilitate highly enantioselective Cu(I)-catalysed propargylic amination of both aliphatic and aryl ketone-derived propargylic carbonates to give α-tertiary ethynylamines. Related tandem sequences are reported to synthesize quaternary azacycles.

Alkane carbonylation through photocatalytic alkyl radical addition to CO is a challenge. Now, an equilibrium-leveraging strategy which combines the direct carbonylation of alkanes with CO with onwards enantioselective transformations is reported, providing an enantioselective method for the synthesis of β-amino and α-amino ketones.

Enantioselective triple [2 + 2 + 2] cycloadditions are reported that enable the synthesis of 3D π-extended carbo[11] and [13]helicenes, which show excellent circularly polarized luminescence brightness (up to 513 M⁻¹ cm⁻¹), the highest value among helicene derivatives.

Direct and site-selective C–H functionalization of alkenes under environmentally benign conditions represents a useful and attractive yet challenging transformation to access value-added molecules. Here, the authors report a protocol for a variety of intermolecular Heck-type functionalization of C(sp2)–H bond of alkenes by thianthrenation.

Combining data science and organic synthesis to achieve the rapid and precise creation of complex molecules while controlling multiple selectivities is an emerging trend, but few successful examples are reported. Here, the authors develop an artificial neural network regression model using bond orbital data to predict chemical reactivities.

Macrolactones exhibit distinct conformational and configurational properties and are widely found in natural products but catalysts to govern both macrolactone formation and stereochemical control remain largely unexplored. Here, the authors disclose an N-heterocyclic carbene (NHC)-catalyzed enantioselective synthesis of chiral macrolactones varying in ring size from sixteen to twenty members that feature distinct configurationally stable planar stereogenicity.

Molecular editing has been used for the late-stage functionalization of chemical scaffolds at the atomic level, however, chemically editing carbohydrates by inserting a foreign glycan remains underexplored. Here, the authors develop a cut-insert-stitch editing reaction sequence to insert various carbohydrates and activated hydroxyacids into oligosaccharides.

Sulfur fluoride exchange (SuFEx), a new type of linkage reaction, has great potential for application in functional molecule linkage to prepare pharmaceuticals, biomolecules, and polymers. Herein, the authors report the synthesis of a range of sulfoximines through SuFEx reaction between sulfonimidoyl fluorides and aryl/alkyl organotrifluoroborates.

The rapid generation of molecular complexity from a given molecular scaffold is crucial to drug discovery and development. Now the chemodivergent molecular editing of indoles using fluoroalkyl carbenes has been developed to modularly access four different types of fluorine-containing N-heterocyclic compound with high molecular complexity.

All-carbon quaternary stereocenters are an important synthetic motif but are especially difficult to synthesize enantioselectively. Here, the authors demonstrate the organocatalytic regio- and enantioselective synthesis of valuable acyclic 1,4-dicarbonyl products with vinylated and arylated quaternary centers.

Developing efficient methods for the formation and cleavage of amide species is a primary research goal, but the amide C–N bond cleavage is exceptionally challenging. Here, the authors report the development of an organocatalyst that can effectively catalyze the atroposelective ring-opening of biaryl lactams via amide C–N bond cleavage.

The generation of Fischer-type carbene complexes for organic synthesis usually requires stoichiometric amounts of metal. Now the palladium-catalysed formation of a Fischer-type carbene intermediate for the synthesis of β-lactam derivatives is described and its crystal structure is solved.

Characterizing highly-reactive glycosyl cation intermediates and understanding their glycosylation mechanisms are essential to the stereoselective synthesis of complex carbohydrates. Here the authors report a workflow that is utilized to characterize rhamnosyl 1,3-bridged dioxanium ions derived from C-3 p-anisoyl esterified donors.

Merging photoredox and biocatalysis provides opportunities to address challenges in synthetic chemistry. Now the combination of a ruthenium photocatalyst for oxidative radical formation and ‘ene’-reductases for radical interception enables an enantiodivergent decarboxylative alkylation reaction.