Volume 2 Issue 12, December 2023

Enantioselective electrocatalysis is emerging as an increasingly versatile tool in organic synthesis. Now, by applying asymmetric Lewis acid catalysis with an elaborated ligand design, radical electrochemical amination is accomplished with full selectivity control.

A hybrid carbon nanotube/molecular catalyst achieves highly selective electrochemical conversion of CO to methanol via mechanistic-guided optimizations.

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.

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.

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.

Enantioselective synthesis of medium-sized rings by organocatalytic cycloadditions offers opportunities that are complementary to metal-catalysed cycloadditions. This Review discusses the ability of organocatalytic cycloadditions to synthesize stereodefined medium-sized ring architectures, critically evaluates current synthetic strategies, and highlights avenues for further development.

The synthesis of polycyclic conjugated hydrocarbons with antiaromatic moieties is realized by the thermal rearrangement of dibromomethylene-functionalized molecular precursors on a hot Au(111) metal surface.

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.

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.

The electroreduction of CO to methanol catalysed by supported cobalt phthalocyanine molecules is hindered by low selectivity and poor mechanistic understanding. Here a mechanism-guided reaction based on systematic kinetic studies is used to achieve an improved methanol Faradaic efficiency of roughly 85%.

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.

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.

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 reversible deactivation process in polymerization using chain-end hydrogen atoms remains underexplored and difficult to control. Now, deprotonation–protonation equilibrium-driven C(sp³)–H alkylation polymerization of cyclopropanes is reported using the cooperative catalysis of an organic base and a metal salt to control the polymerization.