Finn Moeller

Nature Communications, Published online: 12 August 2024; doi:10.1038/s41467-024-50945-2

Carbocations are useful synthetic intermediates which enable direct functionalization of carbon centers, but their generation in a manner that uses mild conditions and enables stereoselective interception remains a longstanding goal of organic chemists. Here, the authors use electrochemical enamine oxidation to synthesize chiral scaffolds from racemic α-branched aldehydes.

We developed an efficient strategy for meta- and C5-selective C−H sulfonylation of pyridines using transient enamine-type intermediates from N-amidopyridinium salts. This process utilizes EDA complexes, achieving high selectivity without external photocatalysts. Our method offers late-stage functionalization capabilities that expand the pyridine modification toolbox and provide access to challenging meta-sulfonylated pyridines.

Abstract

The functionalization of pyridines is crucial for the rapid construction and derivatization of agrochemicals, pharmaceuticals, and materials. Conventional functionalization approaches have primarily focused on the ortho- and para-positions, while achieving precise meta-selective functionalization, particularly at the C5 position in substituted pyridines, remains a formidable challenge due to the intrinsic electronic properties of pyridines. Herein, we present a new strategy for meta- and C5-selective C−H sulfonylation of N-amidopyridinium salts, which employs a transient enamine-type intermediate generated through a nucleophilic addition to N-amidopyridinium salts. This process harnesses the power of electron donor-acceptor complexes, enabling high selectivity and broad applicability, including the construction of complex pyridines bearing valuable sulfonyl functionalities under mild conditions without the need for an external photocatalyst. The remarkable C5 selectivity, combined with the broad applicability to late-stage functionalization, significantly expands the toolbox for pyridine functionalization, unlocking access to previously unattainable meta-sulfonylated pyridines.

We report the synthesis of cyclohexanone oxime via the electroreduction of phenol and hydroxylamine using in situ generated cyclohexanone species. Utilizing an optimal Cu catalyst, we achieved a Faradaic efficiency of 69.1 %, a formation rate of 82.0 g h⁻¹ g_cat ⁻¹, and a 97.5 % conversion rate of phenol to oxime. Additionally, a tandem catalytic route enabled the conversion of 4.0 g of lignin to 0.40 g of caprolactam.

Abstract

Coupling in situ generated intermediates with other substrates/intermediates is a viable approach for diversifying product outcomes of catalytic reactions involving two or multiple reactants. Cyclohexanone oxime is a key precursor for caprolactam synthesis (the monomer of Nylon-6), yet its current production uses unsustainable carbon sources, noble metal catalysts, and harsh conditions. Herein, we report the first work to synthesize cyclohexanone oxime through electroreduction of phenol and hydroxylamine. The Faradaic efficiency reached 69.1 % over Cu catalyst, accompanied by a corresponding cyclohexanone oxime formation rate of 82.0 g h⁻¹ g_cat ⁻¹. In addition, the conversion of phenol was up to 97.5 %. In situ characterizations, control experiments, and theoretical calculations suggested the importance of balanced activation of water, phenol, and hydroxylamine substrates on the optimal metallic Cu catalyst for achieving high-performance cyclohexanone oxime synthesis. Besides, a tandem catalytic route for the upgrading of lignin to caprolactam has been successfully developed through the integration of thermal catalysis, electrocatalysis, and Beckmann rearrangement, which achieved the synthesis of 0.40 g of caprolactam from 4.0 g of lignin raw material.

A most common cubic phase in lyotropic (surfactant-water) systems, the “plumber's nightmare” labyrinth, has never been found in thermotropic liquid crystals. Here the first example is reported. Intriguingly, removal of just a methyl branch from the fluorescent mesogen's six alkyls converts the double-network cubic into an array of counter-twisting helices.

Abstract

Gyroid, double diamond and the body-centred “Plumber's nightmare” are the three most common bicontinuous cubic phases in lyotropic liquid crystals and block copolymers. While the first two are also present in solvent-free thermotropics, the latter had never been found. Containing six-fold junctions, it was unlikely to form in the more common phases with rod-like cores normal to the network columns, where a maximum of four branches can join at a junction. The solution has therefore been sought in side-branched mesogens that lie in axial bundles joined at their ends by flexible “hinges”. But for the tightly packed double framework, geometric models predicted that the side-chains should be very short. The true Plumber's nightmare reported here, using fluorescent dithienofluorenone rod-like mesogen, has been achieved with, indeed, no side chains at all, but with 6 flexible end-chains. Such molecules normally form columnar phases, but the key to converting a complex helical column–forming mesogen into a framework-forming one was the addition of just one methyl group to each pendant chain. A geometry-based explanation is given.

Asymmetric Catalysis. The design and evolution of an enzyme for the asymmetric Michael addition of cyclic ketones to nitroolefins by enamine catalysis is reported by Zhi Zhou et al. in their Communication (e202404312).

Nature Chemistry, Published online: 05 August 2024; doi:10.1038/s41557-024-01594-x

Cross-coupling reactions are among the most important carbon–carbon bond-forming reactions. Now the nickel-catalysed cross-coupling of chiral sulfones with Grignard reagents has been achieved with up to 99% retention of chirality. The speed of the cross-coupling relative to sulfone deprotonation and racemization is critical to enabling this enantiospecific process.

The electrochemical parameters for the in situ generation of BH₃ from NaBH₄ at the anode utilising electrochemically generated I₂ were optimised. As model system 4-fluoroacetophenone was used in the asymmetric reduction with the CBS-catalyst to afford the desired secondary alcohol in excellent yield and enantioselectivity.

Abstract

The aim of this investigation was to explore the possibility to perform an asymmetric reduction, utilising a CBS-type catalyst, of prochiral aryl methyl ketones under electrochemical conditions to generate the needed BH₃ upon oxidation of NaBH₄ with in situ generated I₂ in the anode compartment. Therefore, various electrochemical parameters were optimised to conduct the desired formation of the chiral secondary alcohols in high to quantitative yields with a high stereochemical induction, although the catalyst loading had to be chosen relatively high to concur with the racemic reduction of the ketones by the electrogenerated BH₃.

Total synthesis of (+)-kalmanol was achieved by using a Rh-catalyzed [5+2+1] cycloaddition reaction to construct 5/5/8 tricyclic skeleton, aldol/elimination reaction to assemble the 5/5/8/5 tetracyclic skeleton, and a meticulously designed sequence of stereoselective oxidations.

Abstract

Kalmanol, the flagship member of the kalmane diterpene family, possesses a complex and highly oxidized 5/5/8/5 tetracyclic skeleton with nine contiguous stereocenters and exhibits significant analgesic effects and cardiotoxic properties. We have achieved the efficient total synthesis of (+)-kalmanol in 22 steps with 2.3 % yield. The synthesis featured a Rh-catalyzed [5+2+1] cycloaddition reaction to construct 5/5/8 tricyclic skeleton, and a meticulously designed sequence of stereoselective oxidations of the 5/5/8/5 tetracyclic skeleton.

An atom-efficient domino strategy maximizing the yield of non-phenolic dealkylated aromatics from the lignin β-O-4 motif by one-pot catalytic cascade, consisting of selective dehydrogenation of γ-carbinol group, retro-aldol to cleave C−C bonds, and decarbonylation of the generated aldehydes.

Abstract

Aromatic monomers obtained by selective depolymerization of the lignin β-O-4 motif are typically phenolic and contain (oxygenated) alkyl substitutions. This work reveals the potential of a one-pot catalytic lignin β-O-4 depolymerization cascade strategy that yields a uniform set of methoxylated aromatics without alkyl side-chains. This cascade consists of the selective acceptorless dehydrogenation of the γ-hydroxy group, a subsequent retro-aldol reaction that cleaves the C_α−C_β bond, followed by in situ acceptorless decarbonylation of the formed aldehydes. This three-step cascade reaction, catalyzed by an iridium(I)-BINAP complex, resulted in 75 % selectivity for 1,2-dimethoxybenzene from G-type lignin dimers, alongside syngas (CO : H₂≈1.4 : 1). Applying this method to a synthetic G-type polymer, 11 wt % 1,2-dimethoxybenzene was obtained. This versatile compound can be easily transformed into 3,4-dimethoxyphenol, a valuable precursor for pharmaceutical synthesis, through an enzymatic catalytic approach. Moreover, the hydrodeoxygenation potential of 1,2-dimethoxybenzene offers a pathway to produce valuable cyclohexane or benzene derivatives, presenting enticing opportunities for sustainable chemical transformations without the necessity for phenolic mixture upgrading via dealkylation.

Nature Communications, Published online: 01 August 2024; doi:10.1038/s41467-024-50683-5

Lactobacillus species do not produce 1-acetyl-β-carboline

Nature Communications, Published online: 01 August 2024; doi:10.1038/s41467-024-50684-4

Reply to: Lactobacillus species do not produce 1-acetyl-β-carboline

Nature Communications, Published online: 27 July 2024; doi:10.1038/s41467-024-50643-z

Electrochemistry offers tunable, cost effective and environmentally friendly alternatives to carry out redox reactions but the use of organoiodine compounds as electrocatalysts is largely underdeveloped. Here, the authors report an environmentally benign iodine(I/III) electrocatalytic platform for the in situ generation of dichloroiodoarenes for different reactions within a continuous flow setup.