Research Briefing in 2023

A β-lactone compound — globilactone A — has been discovered through genome mining and heterologous expression of a biosynthetic gene cluster. Biosynthetic investigations unveiled the mechanism of the formation of the cyclopentane-β-lactone core.

Design principles are established for the colloidal synthesis of core–shell nanoparticles, which serve as precursors for the general and predictable synthesis of high-entropy alloy nanoparticles as monodisperse samples.

A chemoenzymatic strategy is introduced whereby a glycan backbone is assembled enzymatically to give a core oligosaccharide that is subjected to chemical manipulations to install terminal epitopes. A library of oligosaccharides containing the human natural killer-1 epitope was synthesized, enabling evaluation of the binding specificities of serum antibodies of patients with anti-myelin-associated glycoprotein neuropathy.

A strategy for the transition-metal-free C(sp²)−C(sp³) cross-coupling of α-(pseudo)halo aliphatic ketones and arylboronic acids via a 1,4-metallate shift is demonstrated. The reaction proceeds under mild conditions in the presence of base, and offers an operationally simple method for the construction of C(sp²)−C(sp³) bonds.

A strategy for the cobalt-catalysed allylic fluoroalkylation of terpenes can provide site-selective access to various fluorine-containing motifs under mild conditions. The extension of the protocol to a 2-mol-scale synthesis indicates the scalability of this method.

Chiral macrocycles are of interest for various applications, including drug discovery, but are challenging to synthesize. Now, a method for enantiocontrolled macrocyclization is demonstrated, involving the confinement of a linear substrate within a self-assembled chiral capsule. This method shows good substrate scope and affords chiral macrocycles with high enantioselectivities and conversions.

The most popular reactions used by medicinal chemists are often incompatible with nanoscale ultrahigh-throughput experimentation (ultraHTE). Now, a set of ultraHTE-amenable reaction conditions is reported for four of the most important transformations in drug discovery, and their generality and scalability tested on a range of complex natural products and drug candidates.

A mild and efficient electrochemical strategy has been developed for the multicomponent 1,4-arylalkylation, unsymmetrical dialkylation and hydro(deutero)alkylation of 1,3-enynes with aryl and alkyl bromides as cross-coupling partners. This protocol can be used to synthesize diverse allenes bearing various functionalities, including allenes found in natural products and drugs.

Cyclic iminium salts are used as versatile intermediates in the synthesis of diverse N-(hetero)aryl piperidines. This method facilitates the C2 and/or C3 functionalization of the piperidine backbone with motifs relevant to medicinal chemistry, enabling the exploration of previously inaccessible chemical space for the discovery of medicines.

A strategy to synthesize well-defined main-chain fluoropolymers from gaseous fluoroalkenes under ambient conditions is developed. This general approach allows for the facile tailoring of the sequence and topology of fluoropolymers comprising various comonomers.

Solar-driven photosynthesis offers a sustainable approach to directly producing hydrogen peroxide from oxygen and water but remains inefficient owing to the low photocatalytic efficiency of reported photocatalysts. Now, a Ga–N₅ atomic site on macroporous inverse-opal-type carbon nitride is introduced for the visible-light-driven photosynthesis of hydrogen peroxide with a solar-to-chemical conversion efficiency of 0.4%.

Discrete chiral nanotubes have been synthesized with high efficiency by connecting rim-desymmetrized macrocycles through dynamic covalent linkages. These 2-nm long and 4.7-Å wide helical covalent organic pillars, resolved by chromatography and characterized by X-ray crystallography, show strong binding affinities for linear guest molecules with complementary lengths and electronic densities.

A strategy for the Ni-catalysed hydrodimerization of two unactivated terminal alkenes to selectively afford linear or methyl-branched alkyl–alkyl products is demonstrated. This method offers a solution to the long-standing challenge of connecting alkenes head-to-head and provides a facile approach to constructing C(sp³)–C(sp³) bonds from readily accessible alkenes.

A modular and general method to make unprotected aryl C-glycosides with high stereoselectivity from simple starting materials has been developed based on photoredox, Ni-catalysed cross-coupling. Key to success is the use of an allyl glycosyl sulfone in combination with tolyl sulfinate as the synthetic equivalent of a glycosyl anion.

Conventional synthesis of noble/non-noble metal alloy nanocrystals lacks control over metal co-reduction. An interfacial co-reduction strategy involving active hydrogen is developed that overcomes the difference in the reduction potential of the metals to enable the controlled synthesis of alloy nanostructures with precise and broadly tunable compositions.

Preventing metal deposition by cathodic reduction is a formidable challenge during transition-metal-catalysed electrosynthesis under direct current (d.c.) electrolysis. Now, an asymmetric-waveform alternating current (a.c.) electrolysis protocol is developed for Ag-catalysed C–H phosphorylation. The a.c.-based approach regenerates the Ag catalyst and maintains a dynamic balance of catalyst loading.

Reductive anti-1,2-dimetallation of alkynes proceeds through the use of sodium dispersion as a reducing agent and an organomagnesium or organoaluminum halide as a reduction-resistant electrophile. The reaction stereoselectively generates trans-1,2-dimagnesio- or 1,2-dialuminoalkenes, which show useful reactivity.