Electrocatalytic Access to Azetidines via Intramolecular Allylic Hydroamination: Scrutinizing Key Oxidation Steps through Electrochemical Kinetic Analysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(28), С. 15360 - 15369

Опубликована: Июль 10, 2023

Azetidines are prominent structural scaffolds in bioactive molecules, medicinal chemistry, and ligand design for transition metals. However, state-of-the-art methods cannot be applied to intramolecular hydroamination of allylic amine derivatives despite their underlying potential as one the most prevalent synthetic precursors azetidines. Herein, we report an electrocatalytic method sulfonamides access azetidines first time. The merger cobalt catalysis electricity enables regioselective generation key carbocationic intermediates, which could directly undergo C-N bond formation. mechanistic investigations including electrochemical kinetic analysis suggest that either catalyst regeneration by nucleophilic cyclization or second oxidation intermediate is involved rate-determining step (RDS) our protocol highlight ability electrochemistry providing ideal means mediate oxidation.

Язык: Английский

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Mechanism of Alkene Hydrofunctionalization by Oxidative Cobalt(salen) Catalyzed Hydrogen Atom Transfer

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(4), С. 2685 - 2700

Опубликована: Янв. 16, 2024

Oxidative MHAT hydrofunctionalization of alkenes provides a mild cobalt-catalyzed route to forming C–N and C–O bonds. Here, we characterize relevant salen-supported cobalt complexes their reactions with alkenes, silanes, oxidant, solvent. These stoichiometric investigations are complemented by kinetic studies the catalytic reaction catalyst speciation. We describe solution characterization an elusive cobalt(III) fluoride complex, which surprisingly is not species that reacts silane under conditions; rather, aquo complex more active. Accordingly, addition water (0.15 M) speeds reaction, show enables product formation in 2 h at −50 °C acetone. Under these conditions, resting states can be observed UV–vis spectrophotometry, including cobalt(III)-alkyl complex. It comes from transient hydride formed turnover-limiting step cycle. This readily degrades but H2; it releases H+ through bimetallic pathway explains [Co]2 dependence off-cycle reaction. In contrast, rate follows power law kobs[Co]1[silane]1. Because different [Co] degradation lower loading improves yield reducing relative unproductive silane/oxidant consumption. illuminate mechanistic details oxidative lay groundwork for understanding other mediated alkyl complexes.

Язык: Английский

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Cobalt‐Catalyzed Enantioselective Hydroamination of Arylalkenes with Secondary Amines

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(2)

Опубликована: Ноя. 7, 2022

Abstract Catalytic asymmetric hydroamination of alkenes with Lewis basic amines is great interest but remains a challenge in synthetic chemistry. Here, we developed Co‐catalyzed arylalkenes directly using commercially accessible secondary amines. This process enables the efficient access to valuable α ‐chiral tertiary good excellent yields and enantioselectivities. Mechanistic studies suggest that reaction includes CoH‐mediated hydrogen atom transfer (MHAT) arylalkenes, followed by pivotal catalyst controlled S N 2‐like pathway between situ generated electrophilic cationic alkylcobalt(IV) species free radical‐polar crossover strategy not only provides straightforward alternative approach for synthesis enantioenriched ‐tertiary amines, also underpins substantial opportunities developing radical functionalization various nucleophiles oxidative MHAT catalysis.

Язык: Английский

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Constructing Four-Membered Heterocycles by Cycloisomerization

ACS Catalysis, Год журнала: 2023, Номер 13(7), С. 4101 - 4110

Опубликована: Март 10, 2023

Four-membered heterocycles are highly sought after in modern drug discovery as they provide beneficial properties to the target molecules. Despite tremendous efforts by synthetic research community, there is a need for simple and new method incorporate these motifs into design Herein, we reveal cycloisomerization strategy construction of oxetane azetidine rings via metal hydride hydrogen atom transfer/radical polar crossover, which challenging both enthalpically entropically. This suitable synthesizing polysubstituted four-membered heterocycles. mild functional-group tolerant reaction has broad substrate scope, including spiro structure, an important motif research. Various heterocyclic building blocks can be synthesized product derivatization. We also discuss mechanism, focusing on ring formation, deuterium experiments DFT studies.

Язык: Английский

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Cobalt-catalyzed HAT reaction for asymmetric hydrofunctionalization of alkenes and nucleophiles

Chem Catalysis, Год журнала: 2023, Номер 3(3), С. 100526 - 100526

Опубликована: Фев. 13, 2023

Язык: Английский

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Cobalt-Catalyzed Carbon–Heteroatom Transfer Enables Regioselective Tricomponent 1,4-Carboamination

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(12), С. 8508 - 8519

Опубликована: Фев. 21, 2024

Tricomponent cobalt(salen)-catalyzed carbofunctionalization of unsaturated substrates by radical-polar crossover has the potential to streamline access broad classes heteroatom-functionalized synthetic targets, yet reaction platform remained elusive, despite well-developed analogous hydrofunctionalizations mediated high-valent alkylcobalt intermediates. We report herein development a cobalt(salen) catalytic system that enables carbofunctionalization. The entails tricomponent decarboxylative 1,4-carboamination dienes and provides direct route aromatic allylic amines obviating preformed allylation reagents protection oxidation-sensitive amines. merges acridine photocatalysis with regioselective 1,4-carbofunctionalization facilitates radical polar phases coupling process, revealing critical roles reactants, as well ligand effects nature formal species on chemo- regioselectivity.

Язык: Английский

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Remote Hydroamination of Disubstituted Alkenes by a Combination of Isomerization and Regioselective N–H Addition

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(7), С. 3875 - 3881

Опубликована: Фев. 13, 2023

Remote hydrofunctionalizations of alkenes incorporate functional groups distal to existing carbon–carbon double bonds. While remote carbonylations are well-known, most common for addition relatively nonpolar B–H, Si–H, and C–H bonds with alkenes. We report a system the hydroamination disubstituted functionalize an alkyl chain selectively at subterminal, unactivated, methylene position. Critical high regioselectivity reaction rates electronic properties substituent on amine development ligand DIP-Ad-SEGPHOS by evaluating steric effects modules reactivity selectivity. The is compatible broad scope aminopyridines enables regioconvergent synthesis amines from isomeric mixture products can be derivatized nucleophilic aromatic substitution amino variety nucleophiles.

Язык: Английский

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Aldehydes as O-Nucleophiles in Cobalt Hydride Hydrogen Atom Transfer Catalysis: Overriding the Innate Somophilicity

Organic Letters, Год журнала: 2023, Номер 25(5), С. 889 - 894

Опубликована: Фев. 1, 2023

In metal hydride-catalyzed alkene hydrofunctionalization reactions via hydrogen atom transfer, simple carbonyl groups have been well-recognized as good somophiles at the carbon for C-C bond formation. Here we report an alternative pathway exploring O-nucleophile to make new C-O bonds during CoH-catalyzed oxidative cyclization of alkenyl aldehydes. This reaction provides a rapid, mild, modular, and stereoselective (up >20:1) entry saturated O-heterocycles nucleophilic trapping in situ-formed oxocarbenium intermediate. The key overriding carbonyl's innate somophilicity was found be promoting formation organocobalt species suppressing radical exchange.

Язык: Английский

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γ-Amino C(sp³)–H Functionalization of Aliphatic Amines through a Light-Driven Triple Catalysis

ACS Catalysis, Год журнала: 2024, Номер 14(10), С. 8005 - 8012

Опубликована: Май 9, 2024

We report intra- and intermolecular γ-amino C(sp3)–H functionalization of aliphatic amines using a vinylsulfone-based HAT (hydrogen atom transfer) auxiliary triple catalysis, which is composed photoredox, cobalt, Brønsted acid catalysts under visible light irradiation. The process accomplishes four elementary steps: (i) electrophilic carbon-centered radical formation on the via MHAT (metal hydride hydrogen reaction, (ii) generation through 1,6-HAT (iii) single-electron oxidation to carbocation equivalents, (iv) nucleophilic substitution with internal or external nucleophiles. As result, this afforded γ-amino-functionalized products, such as azetidines, 1,3-diamine, 1,3-aminoalcohol derivatives.

Язык: Английский

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Cobalt Hydride-Catalyzed Hydroalkynylation of Alkenes with Alkynyl Trifluoroborates

ACS Catalysis, Год журнала: 2024, Номер 14(12), С. 9294 - 9301

Опубликована: Июнь 4, 2024

A cobalt-catalyzed hydroalkynylation of alkenes with alkynyl trifluoroborates is described, proceeding through a cobalt hydride-mediated radical-polar crossover metal hydrogen-atom-transfer process. This method affords structurally diverse alkynyl-containing compounds in high yields under mild conditions and features wide substrate scope, good functional group tolerance, suitability for late-stage functionalization relatively complex natural products bioactive molecules. Expanding the scope to alkenyltrifluoroborate salts further increases utility developed methodology. approach paves an alternative route radical-involved alkynylation alkenylation reactions nucleophilic alkynyl/alkenyl reagents.

Язык: Английский

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