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Suzuki-type cross-coupling for C(sp2)–C(sp3) bond formation with aliphatic halides remains challenging with tertiary aliphatic halides and under transition-metal-free conditions. Now, a transition-metal-free C(sp2)–C(sp3) cross-coupling of α-(pseudo)halo aliphatic ketones with boronic acids via a 1,4-metallate shift is reported which is compatible with tertiary aliphatic halides, allowing for 1,3-disubstituted products.
Developing reaction conditions for radical–radical cross-dehydrogenative amination reactions is challenging. Now a nickel-catalysed asymmetric electrochemical cross-dehydrogenative amination reaction between acylimidazoles and nitrogen nucleophiles is developed to access structurally diverse α-amino carbonyls that can be used to synthesize (+)-γ-secretase inhibitor, (+)-flamprop-methyl and (+)-flamprop-isopropyl.
N-Alkyl amines are prevalent compounds in organic synthesis and medicinal chemistry; however, their synthesis can be impeded by the availability of key reaction components and low selectivity. Now, a metallaphotocatalytic chemo- and regioselective synthesis of N-alkyl anilines is reported that uses readily available tertiary alkylamines, nitroarenes and carboxylic acids.
C(sp3)–H fluoroalkylation of bioactive molecules is a challenge. Now, a scalable and site-selective allylic fluoroalkylation of terpenes and olefins has been developed using a cobaloxime catalyst. Mechanistic studies reveal the process probably proceeds through halogen-atom transfer and hydrogen-atom transfer steps.
Multiple-component cross-coupling reactions can often be unselective and inefficient, making them difficult to develop. Now a chemoselective chromium-catalysed process is reported, forming tertiary alkane centres from benzylic ethers, a Grignard reagent and a silyl chloride, alkyl tosylate or trifluoromethyl-substituted alkene.
The combination of nickel-catalysis and sensitized electron transfer is underdeveloped. Now, a nickel-catalysed sensitized electron transfer method for the synthesis of methyl thioesters from carboxylic acids is reported. Mechanistic investigations reveal that the merger of photocatalytic electron transfer, energy transfer and nickel catalysis plays an essential role in this thioesterification reaction.
Macrocyclization with chirality induction is challenging owing to the entropic penalty associated with ring closure while maintaining chiral conformation. Now, a confinement strategy is reported to achieve chiral macrocyclization and yield an enantiopure product. The chirality of the capsule can be switched to the opposite form by sonication.
The most popular reactions used by medicinal chemists are often incompatible with nanoscale ultrahigh-throughput experimentation (ultraHTE). Now, ultraHTE-amenable reaction conditions are developed through miniaturization of four of the most important drug discovery transformations, and their generality and scalability are tested on a range of natural products and drug candidates.
The synthesis of allenes through 1,4-difunctionalization of 1,3-enynes typically requires preformed organometallic species, high temperature or specific alkyl radical precursors. Now an electrochemical multicomponent protocol for the chemo- and regioselective 1,4-difunctionalization of 1,3-enynes is reported, which uses alkyl bromides with aryl bromides, alkyl bromides or H2O/D2O as reagents for 1,4-difunctionalization.
Piperidine heterocycles are widely prevalent in drug molecules; however, their synthesis remains challenging. Now, a general approach for N-(hetero)aryl piperidine synthesis using isolable iminium salts is reported. A variety of substituents are installed at the C2 and C3 positions, giving access to densely functionalized piperidines that are challenging to obtain using other methods.
Atomically precise graphene fragments are synthesized by using a radical-mediated coupling approach. One open-shell doublet graphene fragment forms a persistent bilayer assembly with highly delocalized 32-centre-2-electron pancake bonding.
Visible-light-driven dual photoredox catalysis often uses expensive metals, such as iridium. Now, a photocatalytic approach using a Ni single-atom carbon nitride catalyst is reported for the C–O cross-coupling of carboxylic acids and alkyl halides, demonstrating broad functional group tolerance, short reaction times, facile recovery and excellent stability.
The synthesis of phosphorous compounds in the 5+ oxidation state typically relies on energy-consuming processes using white phosphorus (P4). Now, a simple approach that cleaves P–O bonds in ubiquitous PV sources to form a PO2+ phosphorylation agent enables the redox-neutral synthesis of various PV chemicals.
Nature uses complex supramolecular reaction networks to regulate structure formation. Now, by creating a photolytic reaction cascade with competing redox pathways, different hierarchical assemblies can be tailored based on a single molecular identity.
By combining coordination, cluster and colloidal chemistry, precision synthesis is realized in cation-exchange reactions of nanoclusters (Cu2Se to CdSe). The precise transformation unveils the origin of chirality and polarity in semiconductor nanomaterials and enables atomic visualization of complex reaction mechanisms.
Cross-coupling reactions are among the most widely used synthetic methods in medicinal chemistry; however, they typically form bonds with C(sp2)-hybridized atoms. The resulting molecules often have suboptimal physicochemical and topological properties. Here virtual and experimental libraries of products from benzylic C(sp3)–H cross-coupling are shown to access underpopulated 3D chemical space.
Carbon-negative biomanufacturing is typically hampered by narrow product scope and light-induced decomposition. Now, an integrated photosynthetic carbon sequestration and cellular catalysis strategy for CO2 valorization are reported. Multiple gene editing and a high-throughput workflow have facilitated its application to the biocatalytic production of styrene, intracellular unstable aldehydes and photosensitive molecules from CO2.
trans-Bis-silylation of alkynes is underdeveloped compared with cis-bis-silylation. Now, a Pd-catalysed method for the trans-bis-silylation of terminal alkynes is reported using disilane reagent 8-(2-substituted 1,1,2,2-tetramethyldisilanyl)quinoline to selectively form trans-bis-silylated alkenes. Mechanistic studies reveal that the reaction probably proceeds through a combined cis-bis-silylation and Z/E isomerization process.
The synthesis of topological molecular carbons with persistent chirality is challenging. Here, a triply twisted Möbius carbon nanobelt was synthesized and its two enantiomers were isolated, showing a large absorption dissymmetry factor.
