A biomimetic S _H 2 cross-coupling mechanism for quaternary sp ³ -carbon formation

Science, Год журнала: 2021, Номер 374(6572), С. 1258 - 1263

Опубликована: Дек. 2, 2021

Bimolecular homolytic substitution (S

Язык: Английский

---

Transition Metal Catalysis Controlled by Hydrogen Bonding in the Second Coordination Sphere

Chemical Reviews, Год журнала: 2022, Номер 122(14), С. 12308 - 12369

Опубликована: Май 20, 2022

Transition metal catalysis is of utmost importance for the development sustainable processes in academia and industry. The activity selectivity complexes are typically result interplay between ligand properties. As can be chemically altered, a large research focus has been on development. More recently, it recognized that further control over achieved by using “second coordination sphere”, which seen as region beyond direct sphere center. Hydrogen bonds appear to very useful interactions this context they have sufficient strength directionality exert second sphere, yet hydrogen dynamic, allowing fast turnover. In review we highlighted several key features bonding summarized use program sphere. Such bridging two ligands coordinated center effectively lead supramolecular bidentate ligands. addition, used preorganize substrate Both strategies catalysts with superior properties variety catalyzed transformations, including (asymmetric) hydrogenation, hydroformylation, C–H activation, oxidation, radical-type photochemical reactions.

Язык: Английский

---

Palladium-Catalyzed Siloxycyclopropanation of Alkenes Using Acylsilanes

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(3), С. 1099 - 1105

Опубликована: Янв. 12, 2022

Currently, catalytically transferable carbenes are limited to electron-deficient and neutral derivatives, electron-rich bearing an alkoxy group (i.e., Fischer-type carbenes) cannot be used in catalytic cyclopropanation because of the lack appropriate carbene precursors. We report herein that acylsilanes can serve as a source under palladium catalysis, enabling range alkenes. This reactivity profile is sharp contrast metal-free siloxycarbenes, which unreactive toward normal The resulting siloxycyclopropanes valuable homoenolate equivalents, allowing rapid access elaborate β-functionalized ketones.

Язык: Английский

---

Diastereoselective Transfer of Tri(di)fluoroacetylsilanes‐Derived Carbenes to Alkenes

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(25)

Опубликована: Апрель 13, 2022

Stereoselective cyclopropanation reaction of alkenes is usually achieved by metal complexes via singlet-metal-carbene intermediates. However, previous transition-metal-catalyzed with acylsilanes afforded low diastereoselectivity. Herein, we report the first visible-light-induced transition-metal-free terminal trifluoroacetylsilanes and difluoroacetylsilanes. Both aromatic aliphatic as well electron-deficient are suitable substrates for highly cis-selective [2+1] cyclization reaction. A combination experimental computational studies identified triplet carbenes being key intermediates in this transformation. The gram scale late-stage functionalization demonstrated synthetic potential strategy.

Язык: Английский

---

Late-Stage C(sp³)–H Methylation of Drug Molecules

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(5), С. 2787 - 2793

Опубликована: Янв. 25, 2023

Methyl groups are well understood to play a critical role in pharmaceutical molecules, especially those bearing saturated heterocyclic cores. Accordingly, methods that install methyl onto complex molecules highly coveted. Late-stage C-H functionalization is particularly attractive approach, allowing chemists bypass lengthy syntheses and facilitating the expedited synthesis of drug analogues. Herein, we disclose direct introduction via C(sp3)-H broad array heterocycles, enabled by merger decatungstate photocatalysis unique nickel-mediated SH2 bond formation. To further demonstrate its synthetic utility as tool for late-stage functionalization, this method was applied range en route an methylated

Язык: Английский

---

Metalloradical Catalysis: General Approach for Controlling Reactivity and Selectivity of Homolytic Radical Reactions

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(20)

Опубликована: Март 13, 2024

Abstract Since Friedrich Wöhler's groundbreaking synthesis of urea in 1828, organic over the past two centuries has predominantly relied on exploration and utilization chemical reactions rooted two‐electron heterolytic ionic chemistry. While one‐electron homolytic radical chemistry is both rich fundamental reactivities attractive with practical advantages, synthetic application been long hampered by formidable challenges associated control reactivity selectivity high‐energy intermediates. To fully harness untapped potential for synthesis, there a pressing need to formulate radically different concepts broadly applicable strategies address these outstanding issues. In pursuit this objective, researchers have actively developing metalloradical catalysis (MRC) as comprehensive framework guide design general approaches controlling stereoselectivity reactions. Essentially, MRC exploits metal‐centered radicals present open‐shell metal complexes catalysts activation substrates generate metal‐entangled key intermediates govern reaction pathway stereochemical course subsequent catalytic processes. Different from conventional transition complexes, operates through utilizing stepwise mechanisms.

Язык: Английский

---

Alkene Hydrobenzylation by a Single Catalyst That Mediates Iterative Outer-Sphere Steps

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(4), С. 2351 - 2357

Опубликована: Янв. 17, 2024

Cross-coupling catalysts typically react and unite functionally distinct partners via sequential inner-sphere elementary steps: coordination, migratory insertion, reductive elimination, etc. Here, we report a single catalyst that cross-couples styrenes benzyl bromides iterative outer-sphere metal–ligand-carbon interactions. Each partner forms stabilized radical intermediate, yet heterocoupled products predominate. The system is redox-neutral and, thus, avoids exogenous oxidants, resulting in simple scalable conditions. Numerous variations of alkene hydrobenzylation are made possible, including access to the privileged heterodibenzyl (1,2-diarylethane) motif challenging quaternary carbon variants.

Язык: Английский

---

The Carbene Chemistry of N-Sulfonyl Hydrazones: The Past, Present, and Future

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

N-Sulfonyl hydrazones have been extensively used as operationally safe carbene precursors in modern organic synthesis due to their ready availability, facile functionalization, and environmental benignity. Over the past two decades, there has tremendous progress chemistry of N-sulfonyl presence transition metal catalysts, under metal-free conditions, or using photocatalysts photoirradiation conditions. Many transfer reactions are unique cannot be achieved by any alternative methods. The discovery novel development highly enantioselective new skeletal editing represent notable recent achievements hydrazones. This review describes overall made hydrazones, organized based on reaction types, spotlighting current state-of-the-art remaining challenges addressed future. Special emphasis is devoted identifying, describing, comparing scope limitations methodologies, key mechanistic scenarios, potential applications complex molecules.

Язык: Английский

---

Asymmetric Radical Cyclopropanation of α,β-Unsaturated Amides with α-Boryl and α-Silyl Dibromomethanes via Cr(II)-Based Metalloradical Catalysis

Journal of the American Chemical Society, Год журнала: 2025, Номер 147(9), С. 7282 - 7292

Опубликована: Фев. 20, 2025

Transition-metal-catalyzed asymmetric carbene-transfer reactions represent a powerful strategy for synthesizing chiral cyclopropanes. However, current methods predominantly rely on stabilized carbene-bearing α-π-conjugated groups, restricting access to less carbenes, such as α-silyl and α-boryl carbenes. Herein, we present an unprecedented Cr(II)-based metalloradical system the cyclopropanation of α,β-unsaturated amides with dibromomethanes in presence Mn reducing agent. Employing chromium complex, reaction proceeds under mild conditions, yielding cyclopropanes three contiguous stereocenters high diastereo- enantioselectivities. This method features Cr-catalyzed radical-based stepwise mechanism. The broad substrate scope, encompassing various amides, demonstrates protocol's versatility robustness. Mechanistic insights, supported by experimental computational studies, suggest formation α-Cr(III)-alkyl radical intermediates, delineating pathway distinct from that classical concerted cyclopropanations. approach provides tool highly functionalized cyclopropanes, offering potential applications drug discovery development.

Язык: Английский

---

Metalloradical Activation of In Situ-Generated α-Alkynyldiazomethanes for Asymmetric Radical Cyclopropanation of Alkenes

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(5), С. 2368 - 2378

Опубликована: Янв. 31, 2022

α-Alkynyldiazomethanes, generated in situ from the corresponding sulfonyl hydrazones presence of a base, can serve as effective metalloradicophiles Co(II)-based metalloradical catalysis (MRC) for asymmetric cyclopropanation alkenes. With D2-symmetric chiral amidoporphyrin 2,6-DiMeO-QingPhyrin optimal supporting ligand, system efficiently activate different α-alkynyldiazomethanes at room temperature highly broad range This catalytic radical process provides general synthetic tool stereoselective construction alkynyl cyclopropanes high yields with both diastereoselectivity and enantioselectivity. Combined computational experimental studies offer several lines evidence support underlying stepwise mechanism Co(II)-catalyzed olefin involving unique α-metalloradical intermediate that is associated two resonance forms α-Co(III)-propargyl γ-Co(III)-allenyl radical. The resulting enantioenriched cyclopropanes, showcased stereospecific transformations, may valuable building blocks organic synthesis.

Язык: Английский

---