Enantioselective C(sp²)–C(sp³) Bond Construction by Ni Catalysis

Accounts of Chemical Research, Год журнала: 2024, Номер 57(5), С. 751 - 762

Опубликована: Фев. 12, 2024

ConspectusAfter decades of palladium dominating the realm transition-metal-catalyzed cross-coupling, recent years have witnessed exciting advances in development new nickel-catalyzed cross-coupling reactions to form C(sp3) centers. Nickel possesses distinct properties compared with palladium, such as facile single-electron transfer electrophiles and rapid C–C reductive elimination from NiIII. These properties, among others, make nickel particularly well-suited for (RCC) which two are coupled an exogenous reductant is used turn over metal catalyst. Ni-catalyzed RCCs use readily available stable starting materials exhibit good functional group tolerance, makes them appealing applications synthesis complex molecules. Building upon foundational work by groups Kumada, Durandetti, Weix, well advancements enantioselective redox-neutral cross-couplings led Fu co-workers, we initiated a program explore feasibility developing highly RCCs. Our research has also been driven keen interest unraveling factors contributing enantioinduction electrophile activation seek avenues advancing our understanding further these reactions.In first part this Account, organize reported methods on basis identity electrophiles, including benzylic chlorides, N-hydroxyphthalimide (NHP) esters, α-chloro esters nitriles. We highlight how selection specific chiral ligands plays pivotal role achieving high cross-selectivity enantioselectivity. In addition, show that reduction can be accomplished not only heterogeneous reductants, Mn0, but soluble organic tetrakis(dimethylamino)ethylene (TDAE), electrochemically. The homogeneous TDAE, suited studying mechanism transformation. Although Account primarily focuses RCCs, using trifluoroborate (BF3K) salts radical precursors dual-Ni/photoredox systems.At end summarize relevant mechanistic studies closely related asymmetric alkenylation developed laboratory provide context between others. discuss ligand influence rates mechanisms mode generation optimize yield RCC. endeavors offer insights intricate at play goal rate improve substrate scope anticipate share guidance field.

Язык: Английский

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Stereoselective amino alcohol synthesis via chemoselective electrocatalytic radical cross-couplings

Nature Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Язык: Английский

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A decarbonylative approach to alkylnickel intermediates and C(sp ³ )-C(sp ³ ) bond formation

Science, Год журнала: 2024, Номер 385(6715), С. 1331 - 1337

Опубликована: Сен. 19, 2024

The myriad nickel-catalyzed cross-coupling reactions rely on the formation of an organonickel intermediate, but limitations in forming monoalkylnickel species have limited options for C(sp 3 ) cross-coupling. monoalkylnickel(II) from abundant carboxylic acid esters would be valuable, derivatives are primarily decarboxylated to form alkyl radicals that lack correct reactivity. In this work, we disclose a facile oxidative addition and decarbonylation sequence forms intermediates through nonradical process. key ligand, bis(4-methylpyrazole)pyridine, accelerates decarbonylation, stabilizes alkylnickel(II) destabilizes off-cycle nickel(0) carbonyl species. utility new reactivity )-C(sp bond is demonstrated reaction challenging by purely radical methods—the selective primary with iodides.

Язык: Английский

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Ni-catalyzed enantioselective three-component reductive alkylacylation of alkenes: modular access to structurally complex α-amino ketones

Chemical Science, Год журнала: 2024, Номер 15(37), С. 15489 - 15495

Опубликована: Янв. 1, 2024

Nickel-catalyzed three-component reductive dicarbofunctionalization of activated olefins (enamides) is presented.

Язык: Английский

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Enantioselective Alkyl–Acyl Radical Cross-Coupling Enabled by Metallaphotoredox Catalysis

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Radical-radical cross-coupling (RCC) offers a promising approach for carbon-carbon bond formation in organic synthesis, particularly creating complex, three-dimensional molecules. However, achieving both cross- and enantioselectivity RCC reactions has remained significant challenge. Here, we report novel metallaphotoredox platform that enables highly enantioselective decarboxylative coupling of carboxylic acid derivatives with aldehydes. Our strategy leverages independent control over radical generation subsequent through fine-tuning common photocatalyst simple chiral bis(oxazoline) nickel catalyst. This redox-neutral protocol requires no exogenous oxidants or reductants demonstrates broad substrate scope functional group compatibility the synthesis enantioenriched α-aryl α-amino ketones. The ketone products can be readily transformed into valuable β-amino alcohols, streamlining access to these important motifs. Furthermore, showcase potential this more challenging C(sp3)-C(sp3) alkyl-alkyl reactions. unified alkyl-acyl represents advance asymmetric catalysis underscores exploit new mechanisms solve long-standing synthetic problems.

Язык: Английский

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A General Direct Aldehyde C–H Alkylation via TBADT-Nickel Synergistic Catalysis

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Herein, we present a nickel/tetrabutylammonium decatungstate (TBADT)-catalyzed protocol for general C-H alkylation of aldehydes, enabling the efficient synthesis aliphatic ketones through ligand-controlled cross-coupling. This mild and cost-effective methodology demonstrates broad substrate compatibility with various commercially available aldehydes both activated unactivated alkyl bromides, delivering target products in high yields. Notably, practical utility this catalytic system has been highlighted concise two-step valuable musk odorant Aurelione from readily starting materials.

Язык: Английский

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Total syntheses of (–)-macrocalyxoformins A and B and (–)-ludongnin C

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 18, 2024

Abstract The complex and diverse molecular architectures along with broad biological activities of ent -kauranoids natural products make them an excellent testing ground for the invention synthetic methods strategies. Recent efforts notwithstanding, access to highly oxidized enmein-type still presents considerable challenges chemists. Here, we report enantioselective total syntheses C-19 oxygenated -kauranoids, including (–)-macrocalyxoformins A B (–)-ludongnin C, discussion study enabling feature in our synthesis is a devised Ni-catalyzed decarboxylative cyclization/radical-polar crossover/ C -acylation cascade that forges THF ring concomitantly β- keto ester group. Mechanistic studies reveal process this reaction achieved through carboxylation followed by situ esterification. Biological evaluation these reveals indispensable role ketone on D their anti-tumor efficacy.

Язык: Английский

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Versatile, Modular, and General Strategy for the Synthesis of α-Amino Carbonyls

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(35), С. 24699 - 24707

Опубликована: Авг. 24, 2024

Modulating the basicity of alkylamines is a crucial factor in drug design. Consequently, with proximal amide, ester, or ketone have become privileged features many pharmaceutical candidates. The impact α-amino carbonyls has made development new methods for their preparation continuous challenge synthesis. Here, we describe practical strategy that provides modular and programmable synthesis wide range carbonyls. generality this process possible by an extremely mild method to generate carbamoyl radicals, proceeding via Lewis acid-visible-light-mediated Norrish type-I fragmentation tailored carboxamide reagent intercepted through addition situ generated unbiased imines. Aside from reaction's broad scope each component, its capacity draw on plentiful diversely populated amine carbonyl feedstocks showcased two-dimensional array used construct library novel, assay-ready, amides.

Язык: Английский

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Highly Enantioselective Decarboxylative Difluoromethylation

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(43), С. 29297 - 29304

Опубликована: Окт. 15, 2024

Organofluorine molecules that contain difluoromethyl groups (CF2H) at stereogenic centers have gained importance in pharmaceuticals due to the unique ability of CF2H act as lipophilic hydrogen bond donors. Despite their potential, enantioselective installation into readily available starting materials remains a challenging and underdeveloped area. In this study, we report nickel-catalyzed decarboxylative difluoromethylation reaction converts alkyl carboxylic acids difluoromethylated products with exceptional enantioselectivity. This Ni-catalyzed protocol exhibits broad functional group tolerance is applicable for synthesizing fluorinated bioisosteres biologically relevant molecules.

Язык: Английский

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Amide-Directed, Rhodium-Catalyzed Regio- and Enantioselective Hydroacylation of Internal Alkenes with Unfunctionalized Aldehydes

Journal of the American Chemical Society, Год журнала: 2023, Номер 146(1), С. 723 - 732

Опубликована: Дек. 20, 2023

Despite the current progress achieved in asymmetric hydroacylations, highly enantioselective catalytic addition of unfunctionalized aldehydes to internal alkenes remains an unsolved challenge. Here, using a coordination-assisted strategy, we developed rhodium-catalyzed regio- and such as enamides β,γ-unsaturated amides. Valuable α-amino ketones 1,4-dicarbonyl compounds were directly obtained with high enantioselectivity from readily available materials.

Язык: Английский

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