Glycosylations promoted by triflate-generating reagents are widespread synthetic methods for the construction of glycosidic scaffolds and glycoconjugates of biological and chemical interest. These processes are thought to proceed with the participation of a plethora of activated high energy intermediates such as the and glycosyl triflates, or even increasingly unstable glycosyl oxocarbenium-like species, among which only -glycosyl triflates have been well characterized under representative reaction conditions. Interestingly, the remaining less accessible intermediates, yet to be experimentally described, seem to be particularly relevant in -selective processes, involving weak acceptors. Herein, we report a detailed analysis of several paradigmatic and illustrative examples of such reactions, employing a combination of chemical, NMR, kinetic and theoretical approaches, culminating in the unprecedented detection and quantification of the true -glycosyl triflate intermediates within activated donor mixtures. This achievement was further employed as a stepping-stone for the characterization of the triflate anomerization dynamics, which along with the acceptor substitutions, govern the stereochemical outcome of the reaction. The obtained data conclusively show that, even for highly dissociative reactions involving -close ion pair (-CIP) species, the formation of the -glycoside is necessarily preceded by a bimolecular → triflate interconversion, which under certain circumstances does become the rate-limiting step. Overall, our results rule out the prevalence of the Curtin-Hammett fast-exchange assumption for most glycosylations and highlight the distinct reactivity properties of and glycosyl triflates against neutral and anionic acceptors.

N‐BODIPYs (diaminoboron dipyrromethenes) are unveiled as a new family of BODIPY dyes with huge technological potential. Synthetic access to these systems has been gained through a judicious design focused on stabilizing the involved diaminoboron chelate. Once stabilized, the obtained N‐BODIPYs retain the effective photophysical behavior exhibited by other boron‐substituted BODIPYs, such as O‐BODIPYs. However, key bonding features of nitrogen compared to those of oxygen (enhanced bond valence and different bond directionality) open up new possibilities for functionalizing BODIPYs, allowing an increase in the number of pendant moieties (from two in O‐BODIPYs, up to four in N‐BODIPYs) near the chromophore and, therefore, greater control of the photophysics. As a proof of concept, the following findings are discussed: (1) the low‐cost and straightforward synthesis of a selected series of N‐BODIPYs; (2) their outstanding photophysical properties compared to those of related effective dyes (excellent emission signatures, including fluorescence in the solid state; notable lasing capacities in the liquid phase and when doped into polymers; improved laser performance compared to the parent F‐BODIPYs); (3) the versatility of the diaminoboron moiety in allowing the generation of multifunctionalized BODIPYs, permitting access to both symmetric and asymmetric dyes; (4) the capability of such versatility to finely modulate the dye photophysics towards different photonic applications, from lasing to chemosensing.

Targeting the interface between DNA quadruplex and duplex regions by small molecules holds significant promise in both therapeutics and nanotechnology. Herein, a new pharmacophore is reported, which selectively binds with high affinity to quadruplex–duplex junctions, while presenting a poorer affinity for G‐quadruplex or duplex DNA alone. Ligands complying with the reported pharmacophore exhibit a significant affinity and selectivity for quadruplex–duplex junctions, including the one observed in the HIV‐1 LTR‐III sequence. The structure of the complex between a quadruplex–duplex junction with a ligand of this family has been determined by NMR methods. According to these data, the remarkable selectivity of this structural motif for quadruplex–duplex junctions is achieved through an unprecedented interaction mode so far unexploited in medicinal and biological chemistry: the insertion of a benzylic ammonium moiety into the centre of the partially exposed G‐tetrad at the interface with the duplex. Further decoration of the described scaffolds with additional fragments opens up the road to the development of selective ligands for G‐quadruplex‐forming regions of the genome.

Glycosyl sulfoxides have gained recognition in the total synthesis of complex oligosaccharides and as model substrates for dissecting the mechanisms involved. Reactions of these donors are usually performed under pre‐activation conditions, but an experimentally more convenient single‐step protocol has also been reported, whereby activation is performed in the presence of the acceptor alcohol; yet, the nature and prevalence of the reaction intermediates formed in this more complex scenario have comparatively received minimal attention. Herein, a systematic NMR‐based study employing both 13C‐labelled and unlabelled glycosyl sulfoxide donors for the detection and monitoring of marginally populated intermediates is reported. The results conclusively show that glycosyl triflates play a key role in these glycosylations despite the presence of the acceptor alcohol. Importantly, the formation of covalent donor/acceptor sulfonium adducts was identified as the main competing reaction, and thus a non‐productive consumption of the acceptor that could limit the reaction yield was revealed.

Invited for the cover of this issue are Andrés G. Santana, Carlos González, Juan Luis Asensio and co‐workers at Instituto de Química Orgánica General, Instituto de Química‐Física Rocasolano and Universidad de La Rioja. The image depicts drug selectivity using a metaphor of an arrow hitting a target. Read the full text of the article at 10.1002/chem.202005026.

: Aromatic platforms are ubiquitous recognition motifs occurring in protein carbohydrate binding domains (CBDs), RNA receptors and enzymes. They stabilize the glycoside/receptor complexes by participating in stacking CH/ interactions with either the - or - face of the corresponding pyranose units. In addition, the role played by aromatic units in the stabilization of glycoside cationic transition states has started being recognized in recent years. Extensive studies carried out during the last decade have allowed to dissect the main contributing forces that stabilize the carbohydrate/aromatic complexes, while helping delineate not only the standing relationship between the glycoside/aromatic chemical structures and the strength of this interaction, but also their potential influence on glycoside reactivity.

The structural motif defined by a G‐quadruplex DNA juxtaposed to duplex regions has been identified as a hot‐spot for molecular recognition, and selectively targeted by a family of benzylamine‐containing derivatives. The understanding of this new mode of interaction was uncovered by the structural dissection of both ligand and receptor contributions. More information can be found in the Full Paper by A. G. Santana, C. González, J. L. Asensio, et al. on page 6204.

The mechanistic study of one‐step sulfoxide glycosylations enabled by the employment of 13C‐labelled glycosyl‐donors and low‐temperature NMR revealed the internal dynamics between all reaction intermediates involved in this process, which are represented in the accompanying image as a molecular rollercoaster. The formation and stability of donor/acceptor sulfonium adducts, inherent to this particular experimental protocol, defines the scope of this synthetic methodology. More information can be found in the Full Paper by A. G. Santana, J. L. Asensio, et al. on page 2030.