Finn Moeller

Regio- and enantioconvergent hydroallylation of acylates under Cu/Pd synergistic catalysis is reported. The incorporation of a silyl group into allyl acetates precisely controls regio- and enantioselectivity through steric hindrance. Subsequent transformation of the silyl group in the product enables the regioselective synthesis of allylated products bearing two distinct yet structurally similar aryl groups.

Abstract

Transition-metal-catalyzed asymmetric allylic substitution provides an efficient route to chiral organic molecules featuring an allyl moiety, key intermediates in the synthesis of biologically active compounds. However, the use of unsymmetrical 1,3-disubstituted allyl electrophiles has been severely constrained by the challenges of achieving both regio- and stereoselectivity simultaneously. Herein, we present γ-silyl-substituted allyl acetates as highly effective electrophiles for a regio- and enantioconvergent hydroallylation, enabling the construction of vicinal stereogenic centers. This method delivers allylated products in 44%–93% yield with 79:21 to >95:5 dr and 88% to >99% ee. Additionally, the silyl group in the products can be readily converted into other functional groups, such as acyl and aryl groups, enhancing their synthetic utility.

A mild, photoinduced radical hydroarylation of unactivated N-allylamine derivatives is reported for the synthesis of β-arylethylamines with simple alkyl chains. DFT studies reveal that ipso attack is more favourable than ortho attack when one of the ortho positions at the aromatic group attached to sulfur was blocked.

Abstract

Arylethylamines are crucial elements in pharmaceutical molecules, making methods for their synthesis highly significant. The Truce–Smiles rearrangement is a well-developed strategy to synthesize arylethylamine motifs via aryl migration. However, most examples require amide substrates to activate the alkene to attack by a radical precursor. This strategy both limits the product scope to amide-containing compounds as well as necessitating the incorporation of specific functional groups arising from the initial radical addition. In this work, we overcome these limitations, delivering a hydrogen-atom transfer from a cobalt catalyst to unactivated alkenes to yield β-arylethylamines with simple alkyl chains. DFT studies reveal that increasing the steric hindrance in at least one of the ortho positions on the migrating aromatic group promotes ipso over ortho addition, a selectivity that contrasts with previous methods.

“My favorite principle is the Hofstadter's Law, which states that a project always takes longer than expected, even when accounting for the law… My group has fun by breaking molecules…”

Find out more about Guillaume De Bo in his Introducing… Profile.

A photoredox/nickel dual-catalyzed enantioselective decarboxylative acylation of α-hydroxy acid derivatives with carboxylic acids has been developed, enabling efficient access to enantioenriched α-oxygenated ketones. This method exhibits a broad substrate scope, good functional group tolerance, high chemoselectivity, and excellent enantioselectivity.

Abstract

Light-driven decarboxylative cross-coupling has emerged as a pivotal platform for constructing C(sp³)–C(sp²) bonds in organic synthesis and medicinal chemistry. However, using two structurally dissimilar carboxylic acids as a feedstock to form chiral α-oxygenated ketones remains a considerable challenge due to side reactions such as decarboxylative reduction and homocoupling. Herein, we report for the first time a photoredox/nickel dual-catalyzed enantioselective decarboxylative acylation of α-hydroxy acid derivatives and aliphatic carboxylic acids, enabling efficient access to enantioenriched α-oxygenated ketones. This method exhibits a broad substrate scope, good functional group tolerance, high chemoselectivity, and excellent enantioselectivity (up to 99% e.e.). The advantage of this reaction is that it eliminates the need for metal reductants and the use of precious metal photocatalysts and utilizes renewable feedstocks. The use of a coiled-tube continuous-flow photoreactor can shorten the illumination time by half and obtain results comparable to those of a batch reaction. Furthermore, preliminary mechanistic experiments support a pathway in which photocatalytic decarboxylation generates α-oxy alkyl radical species, and the Ni(I)–alkyl intermediate activates the in situ–formed mixed anhydride followed by reductive elimination to give the product in enantiomerically pure form.

Nature, Published online: 05 May 2025; doi:10.1038/d41586-025-01359-7

Nature Communications, Published online: 06 May 2025; doi:10.1038/s41467-025-59410-0

We present a one-step deaminative Suzuki–Miyaura-type coupling of anilines via fleeting diazonium intermediate with nitrate and bisulfite as the reagents. This represents the first application of the nitrate reduction strategy in transition metal catalysis of diazonium chemistry. The reaction utilizes low-hazard, readily available starting materials and reagents. Our method demonstrates a simpler and safer procedure, together with the advantage of functional group tolerance and potential application in the arylation of various aniline-containing complex molecules.

Abstract

We present a deaminative Suzuki–Miyaura-type coupling (SMC) of anilines with nitrate as a diazotization reagent, which integrates transition-metal catalysis with nitrate-based diazonium chemistry for the first time. The synergistic reduction of nitrate by bisulfite and boronic acids allows for both oxidative diazotization with low-valent transition metal redox transformations simultaneously. The reaction utilizes low-hazard, readily available starting materials and reagents. In comparison to previous diazonium-based Suzuki–Miyaura-couplings, the in situ oxidation of anilines by reduction of nitrate allows larger functional group tolerance.

We present the first general synthetic strategy for accessing N(CF₃)(CF₂H) amines, which display a 2000-fold increase in stability over N-CF₃ amines. The compounds are synthesized through a desulfurization–fluorination of N-CF₃ thioformamides.

Abstract

With poor metabolic stability being a major cause of failure in drug development, there is a pressing need for strategic molecular modifications to optimize for desired properties and function. N-substitution has emerged as a powerful approach, with N-CF₃ amines previously demonstrating enhanced lipophilicity and reduced susceptibility to oxidation, albeit inherent instability to hydrolysis. This report discloses the further evolution of this motif—the introduction of an additional N-difluoromethyl unit, resulting in an extraordinary 2000-fold increase in stability. We present the first general synthetic strategy for accessing N(CF₃)(CF₂H) amines. The method relies on an operationally simple desulfurization–fluorination strategy of N-CF₃ thioformamides and is characterized by broad functional group tolerance.

The first general synthetic access to N-CH₂F and N-CHRF carbamates, thiocarbamates, formamides, alkynamides, and related compounds is disclosed. The method involves the direct synthesis of carbamoyl fluoride building blocks from readily available amines, followed by their derivatization.

Abstract

This work presents the first general synthetic access to N-CH₂F and N-CHRF carbamates, thiocarbamates, formamides, alkynamides, and related compounds. The synthetic approach employs N-CH₂F and N-CHRF carbamoyl fluorides as versatile strategic building blocks, which can be efficiently synthesized in a single step directly from readily available amines or imines.

A strategy to directly synthesize closo-carboranyl analogs of medicinal chemically important β-arylethylamines from alkenes is reported. This reaction is enabled by the first formation of closo-carboranyl radicals by energy transfer (EnT) catalysis and its unique mechanistic features. Several analogs of known bioactive compounds were obtained after downstream modifications.

Abstract

closo-Carboranes are icosahedral carbon–boron clusters with unique properties and broad applicability. They particularly stand out in the context of drug development as privileged structural motifs for boron neutron capture therapy (BNCT) and as highly hydrophobic bioisosteres for the rotational volume of phenyl rings. Herein, we unveil the synthesis of N-protected carboranyl analogs of β-arylethylamines—widely found structural motifs in biologically active molecules—via a one-step alkene difunctionalization approach. Key for our success were the enabling mechanistic characteristics of energy transfer catalysis which we have used for the first time to generate closo-carboranyl radicals. Downstream modifications gave a series of analogs of amino acids and known N-methyl-d-aspartate receptor (NMDAR) antagonists.

The first total syntheses of rearranged ent-trachylobane diterpenoids (-)-Wallichanol A, (-)-Sanguinolane, and (-)-Wallichanol B were accomplished via a concise sequence featuring an intramolecular [2 + 2] cycloaddition to forge a unique tricyclo[3.3.1.0^{2 ,}⁷]nonane core. Key steps include a selective hydrogen atom transfer (HAT) reduction, Robinson annulation, and aerobic oxidations to α-hydroxy ketones.

Abstract

Herein, we report the first enantioselective total syntheses of three rearranged ent-trachylobane diterpenoids, (–)-Wallichanol A (1), (–)-Wallichanol B (2), and (–)-Sanguinolane (3), using a 13, 17, and 14 step longest-linear sequences respectively, featuring a novel intramolecular [2 + 2] cycloaddition to construct the unique pentacyclic framework containing an unprecedented tricyclo[3.3.1.0^2,7]nonane motif. Other key steps in the synthetic route include a highly challenging, selective alkene reduction via hydrogen atom transfer (HAT), leveraging the thermodynamic preference for a tertiary carbon-centered radical; a Robinson-type annulation to construct the tricyclic terpenoid building block; and applying aerobic oxidation at two distinct points to form α-hydroxy ketones, facilitating the enantioselective syntheses of these diterpenoids.

Nature, Published online: 22 April 2025; doi:10.1038/s41586-025-09011-0

A novel catalytic enantioselective α-ethynylation of oxindoles is realized by virtue of spiropyrrolidine amide (SPA)-triazolium organocation catalysis. Taking advantage of this methodology and development of 1,6-aza-Michael additions with and without an aminolysis process, the collective total synthesis of two types of indole alkaloids was also accomplished.

Abstract

The all-carbon quaternary stereogenic center of oxindoles is a crucial structural element of a broad spectrum of indole alkaloids, imparting these molecules with rigid three-dimensional configurations essential for their biological activities. Here, we present a catalytic asymmetric α-ethynylation reaction of oxindoles taking advantage of the catalysis of a spiropyrrolidine amide (SPA) triazolium. This transformation enables the enantioselective construction of the C3 quaternary carbon stereocenter of oxindoles while introducing a versatile ethynyl functionality. Employment of this methodology has been demonstrated in the divergent total synthesis of indole alkaloids (-)-corynoxine, (-)-isorhynchophylline, (-)-aspidospermidine, and (-)-limaspermidine, featuring a protecting group-dependent 1,6-Michael addition or an aminolysis/1,6-Michael addition sequence to generate two distinct types of spiro-indoles, tailored for different late-stage synthetic purposes.

In this scientific perspective, we intend to provide a coherent framework for the field of magnetocatalysis by highlighting opportunities associated with the use of magnetic fields to activate catalysts. A particular focus will be placed on magnetically induced catalysis , providing an overview on current advances and identifying scientific and technical challenges on the path toward a widespread use of this technology in research and industry.

Abstract

The rapidly growing importance of electrification in the chemical industry opens room for disruptive innovations regarding energy input into catalytic processes. Energy efficiency and dynamics of renewable energy supplies represent important challenges, but the design of catalytic systems to cope with such new frameworks may also stimulate the discovery of new catalyst materials and reaction pathways. In this context, many opportunities arise when catalysts are activated in a rapid, localized, and energy-efficient manner. Among the various concepts to achieve adaptivity in catalysis, magnetic induction heating applied directly at the catalyst or in vicinity of the active site has gained increasing attention recently. In this Scientific Perspective, we provide a coherent framework to the emerging field of catalysis using magnetic fields—and in particular alternating current magnetic fields—to activate catalytic materials and define it as magnetically induced catalysis . Promising approaches and selected examples are described to illustrate the scientific concept and to highlight its broad potential for innovation in catalysis from laboratory to industrial scale.