Finn Moeller

A class of bidentate organotellurium dication catalysts are rationally designed to strengthen the weak chalcogen bonding interactions. The enhanced reactivity enables the first catalytic application of chalcogen bonding in the activation of azetidines via a bidentate activation mode, thereby initiating [4 + 2] cycloaddition reactions with non-activated alkenes and alkynes to access various piperidine and tetrahydropyridine architectures.

Abstract

The application of chalcogen bonding catalysis has been largely confined to benchmark reactions due to the limited structural diversity and activating ability of the catalysts, especially those derived from tellurium. Herein, we present a group of rationally designed bis-telluronium catalysts and realize the first application of chalcogen bonding donor in catalyzing the [4 + 2] cycloaddition reaction between azetidines and non-activated alkenes or alkynes. This chemistry demonstrates excellent functional group tolerance and offers an efficient avenue to access the piperidine and tetrahydropyridine architectures in generally moderate-to-good efficiency. A wide array of mechanistic experiments and DFT calculations have been performed to verify the high activity of the organotellurium catalysts with strong electron-deficient aromatic substituents and to suggest a novel bidentate activation mode between catalyst and azetidine via Te⋯O interaction.

We report a practical, scalable, and stereoselective synthesis of chiral oxazaphosphoramides using an L-serine derivative as a chiral auxiliary. The reaction proceeds through an unusual stereoconvergent nucleophilic substitution at the P(V) center. Electrochemical decarboxylative transformations further diversify the products into three types of chiral oxazaphosphoramides.

Abstract

We report a simple, scalable, and stereoselective synthesis of chiral oxazaphosphoramides using phosphoryl chloride, an L-serine derivative, and various primary and secondary amines. Excellent stereoselectivities (typically >99:1 dr) were achieved via an unexpected, stereoconvergent nucleophilic substitution process, wherein two diastereomers of an oxazaphosphorochloridate intermediate were converted to a single diastereomer of an oxazaphosphoramide via distinct pathways. Electrochemical decarboxylative transformations allowed the products to be further diversified to afford three types of chiral oxazaphosphoramides with different ring substitutions.

Electrochemical dehydration reactions are a fascinating and underexplored field of research in the domain of electrosynthesis. They offer a sustainable alternative to hazardous and harsh dehydration reagents. In this review, the recent progress that has been made in this emerging research topic is surveyed.

Electrochemical dehydration reaction is a fascinating and underexplored field of research, which has started to attract significant attention in recent years. Dehydration reactions are characterized by the formal removal of water in the course of the transformation, and they are among the most fundamental types of reactions found throughout chemistry. Examples are esterification reactions, amidation reactions, and the synthesis of carbon-heteroatom multiple bonds. In general, dehydration reactions are not considered to be redox reactions, because no oxidation states change in the substrate from which water is eliminated or in the dehydration reagent that is utilized. At first glance, there does not seem to be a link between dehydration reactions and redox chemistry. In recent years, however, it has been demonstrated that dehydration reactions can be carried out by electrolysis. Given the enormous importance of dehydration reactions from academic to technical scale, electrochemical dehydration reactions offer a more sustainable approach to such transformations. In this review, the recent progress is surveyed and the opportunities of this new and evolving field are highlighted. Electrochemical dehydration reactions are an interesting new discipline in the emerging domain of electroorganic chemistry, which is currently experiencing a remarkable renaissance to establish itself as a 21st-century technique.

Nature Communications, Published online: 05 September 2025; doi:10.1038/s41467-025-63737-z

Sustainable Nickelaelectro-catalysis provided access β-arylated pyrroles via an efficient anodic dehydrogenative C─H activation.

Abstract

Nickel electrocatalysis has emerged as a powerful strategy for sustainable C─H activation, offering an environmentally benign alternative to traditional methods based on stoichiometric oxidants. We, herein, report a nickela-electrocatalyzed approach for the expedient synthesis of β-arylated pyrroles via a unique multiple dehydrogenative C─H activation approach. Hence, direct C─C bond formation between pyrroles and arenes was enabled, obviating the need for prefunctionalized substrates. The reaction proceeded under electrochemical conditions in a user-friendly undivided cell, utilizing electricity as a traceless oxidant. Mechanistic studies, including cyclic voltammetry, provided support for a nickel(II/III/IV) regime, wherein anodic oxidation facilitates the dehydrogenation and C─H activation paired with the valuable hydrogen evolution reaction (HER). Our findings highlight the potential of electrocatalysis to unlock distinct reaction manifolds and provides a sustainable platform for accessing complex heteroaryl frameworks.

Nature, Published online: 05 September 2025; doi:10.1038/d41586-025-02800-7

The first organocatalytic enantioselective [4 + 4] cycloaddition of furan ortho-quinodimethanes is presented. The reaction proceeds in good yields and with high enantioselectivities allowing for the formation of novel classes of cyclooctanoids. DFT calculations point to an intriguing mechanism, where the stereochemical outcome is attributed to protonation of the catalyst-bound intermediate in the stereo-determining step.

Abstract

The enantioselective [4 + 4] cycloaddition for the construction of cyclooctanoids is a challenging transformation in organic chemistry. Herein, we present the first organocatalytic enantioselective [4 + 4] cycloaddition of furan ortho-quinodimethanes, activated by dearomatization of the heteroaromatic compound, which thereby allows for the cycloaddition with dienes. The [4 + 4] cycloaddition is catalyzed by a quinine-derived primary amine in combination with a chiral phosphoric acid and a carboxylic acid affording cyclooctanoids isolated as a single diastereoisomer in good yields and with up to 94% ee. This reaction concept allows for the formation of cyclooctanoids without benzofusion, as demonstrated by oxidative opening of the furan ring. Computational studies of the reaction mechanism for the [4 + 4] cycloaddition point to a stepwise process. Surprisingly, the stereochemical outcome of the reaction is attributed to protonation of the two organocatalyst-bound cyclooctanoid intermediates leading to a preferred set-up for catalyst elimination to account for the absolute configuration of the cyclooctanoid.

Electrochemical decarboxylative acetoxylation of Fmoc-protected peptides via anodic oxidation of the carboxylic acid is challenging under conventional conditions, due to the lability of the Fmoc protecting group. Using selected cosolvents which can be oxidized at higher potentials than the target carboxylic acid but lower than the protecting group, the electrochemical acetoxylation is enabled under constant current conditions.

The synthesis of peptide-based linkers for antibody-drug conjugates involves an oxidative decarboxylation step. Traditional Hofer–Moest electrolysis conditions are not suitable to achieve this transformation due to the presence of an oxidatively labile Fmoc-protecting group. Herein, a solvent-enabled electrochemical procedure has been established, whereby the solvent electrochemical window prevents degradation of the protecting group. The method has been demonstrated for several relevant peptides in good to very good yields (64–92%).

Nature, Published online: 26 August 2025; doi:10.1038/s41586-025-09551-5

Under Ir-catalyzed conditions, N-2°-alkyl or N-3°-alkyl substituents of diverse tertiary aryl amides can be exchanged with the ortho-aryl C─H bond of the aromatic unit. Related processes allow the intermolecular transfer of N-2°-alkyl substituents, providing a convenient means of introducing difficult-to-install ortho-alkyl units.

Abstract

Under Ir-catalyzed conditions, N-2°-alkyl or N-3°-alkyl substituents of diverse tertiary aryl amides can be exchanged with the ortho-aryl C─H bond of the aromatic unit. These alkyl transfer processes employ a homochiral diphosphonite ligand, and this enforces notable levels of enantioconvergency for non-stereodefined 2°-alkyl substituents. Related processes allow the intermolecular transfer of N-2°-alkyl substituents, providing a convenient means of introducing difficult-to-install ortho-alkyl units.