Nickel-Catalyzed Hydrofluorination in Unactivated Alkenes: Regio- and Enantioselective C–F Bond Formation

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(13), С. 9375 - 9384

Опубликована: Март 21, 2024

Catalytic formation of a regio- and enantioselective C–F bond chiral center from readily available alkenes is crucial goal, yet it continues to pose significant challenges in organic synthesis. Here, we report the regioselective bonds facilitated by NiH catalysis coordination directing strategy that enables precise hydrofluorination both terminal internal alkenes. Notably, have optimized this methodology achieve high enantioselectivity creating aliphatic stereogenic centers especially with β,γ-alkenyl substrates, using tailored Bn-BOx ligand. Another pivotal finding our research identification (+)-nonlinear effect under conditions, allowing for even moderately enantiomerically enriched ligands. Given role fluorine pharmaceuticals synthetic materials, offers essential insights into centers, paving way efficient production valuable fluorinated compounds.

Язык: Английский

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Silanes as a versatile hydride source for Ni–H catalysis: a promising tool for π-hydro functionalization

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(15), С. 4290 - 4317

Опубликована: Янв. 1, 2024

Nickel-catalyzed hydrofunctionalization of π-substrates is a possibly effective method to synthesize several value-added molecular architectures. This review covers the NiH catalyzed reactions alkenes, alkynes and allenes.

Язык: Английский

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NiH-catalyzed C–N bond formation: insights and advancements in hydroamination of unsaturated hydrocarbons

Chemical Science, Год журнала: 2023, Номер 15(2), С. 442 - 457

Опубликована: Дек. 6, 2023

The formation of C-N bonds is a fundamental aspect organic synthesis, and hydroamination has emerged as pivotal strategy for the synthesis essential amine derivatives. In recent years, there been surge interest in metal hydride-catalyzed reactions common alkenes alkynes. This method avoids need stoichiometric organometallic reagents overcomes problems associated with specific compounds that may impact functional group compatibility. Notably, developments have brought to forefront olefinic hydroamidation facilitated by nickel hydride (NiH) catalysis. inclusion suitable chiral ligands paved way realization asymmetric realm olefins. review aims provide an in-depth exploration latest achievements bond through intermolecular catalyzed hydrides. Leveraging this innovative approach, diverse range alkene alkyne substrates can be efficiently transformed into value-added enriched bonds. intricacies are succinctly elucidated, offering concise overview underlying reaction mechanisms. It our aspiration comprehensive will stimulate further progress NiH-catalytic techniques, fine-tune systems, drive innovation catalyst design, foster deeper understanding

Язык: Английский

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Iridium‐Catalyzed Remote Site‐Switchable Hydroarylation of Alkenes Controlled by Ligands

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(41)

Опубликована: Авг. 23, 2023

An iridium-catalyzed remote site-switchable hydroarylation of alkenes was reported, delivering the products functionalized at subterminal methylene and terminal methyl positions on an alkyl chain controlled by two different ligands, respectively, in good yields with to excellent site-selectivities. The catalytic system showed functional group tolerance a broad substrate scope, including unactivated activated alkenes. More importantly, regioconvergent transformations mixtures isomeric were also successfully realized. results mechanistic studies demonstrate that reaction undergoes chain-walking process give [Ar-Ir-H] complex alkene. subsequent processes proceed through modified Chalk-Harrod-type mechanism via migratory insertion alkene into Ir-C bond followed C-H reductive elimination afford hydrofunctionalization site-selectively.

Язык: Английский

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An Engineered Imine Reductase for Highly Diastereo‐ and Enantioselective Synthesis of β‐Branched Amines with Contiguous Stereocenters

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(47)

Опубликована: Авг. 9, 2024

Abstract β‐Branched chiral amines with contiguous stereocenters are valuable building blocks for preparing various biologically active molecules. However, their asymmetric synthesis remains challenging. Herein, we report a highly diastereo‐ and enantioselective biocatalytic approach broad range of β‐branched starting from corresponding racemic ketones. This involves dynamic kinetic resolution‐asymmetric reductive amination process catalyzed using only an imine reductase. Four rounds protein engineering endowed wild‐type Poc IRED higher reactivity, better stereoselectivity, broader substrate scope. Using the engineered enzyme, amine products were synthesized up to >99.9 % ee , >99 : 1 dr conversion. The practicability developed method was confirmed by producing key intermediate tofacitinib in 74 yield, 98 2 at challenging loading 110 g L −1 . Our study provides capable reductase protocol developing efficient reaction system.

Язык: Английский

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Nickel Catalyzed Enantioselective 1,4-Hydroamination of 1,3-Dienes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(27), С. 18440 - 18450

Опубликована: Июль 1, 2024

Transition metal-catalyzed enantioselective hydroamination of 1,3-dienes provides a direct methodology for the construction chiral allylamines. So far, all reported examples used nucleophilic amines and proceeded with 3,4-regioselectivity. Herein, we describe first example nickel-catalyzed 1,4-hydroamination using trimethoxysilane hydroxylamines structurally adaptable aromatic spiroketal based diphosphine (SKP) as ligand, affording wide array α-substituted allylamines in high yields excellent regio- enantioselectivities. This operationally simple protocol demonstrated broad substrate scope functional group compatibility, significantly expanding chemical space Experimental DFT studies were performed to elucidate mechanism rationalize enantioselectivities reaction.

Язык: Английский

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Regiodivergent Hydroamidation of Alkenes via Cobalt-Hydride Catalysis

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

Опубликована: Апрель 10, 2025

Regiodivergent hydroamin(d)ation of alkenes presents a valuable strategy for the synthesis diverse amines or amides from common set starting materials, yet achieving controlled regioselectivity remains significant challenge. In this work, we present cobalt-catalyzed regiodivergent hydroamidation alkenes, enabling enantioselective ipso- and migratory heterocyclic alkenes. The ability to finely tune various reaction parameters allows seamless switch in regioselectivity. Notably, selectivity are governed by choice cobalt catalyst anions. Mechanistic studies reveal neutral Co-H species mediating ipso-hydroamidation cationic intermediate promoting hydroamidation. This protocol exhibits broad substrate scope, high functional group tolerance, provides an efficient pathway synthetizing structurally amides.

Язык: Английский

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Iridium‐Catalyzed Remote Site‐Switchable Hydroarylation of Alkenes Controlled by Ligands

Angewandte Chemie, Год журнала: 2023, Номер 135(41)

Опубликована: Авг. 23, 2023

Abstract An iridium‐catalyzed remote site‐switchable hydroarylation of alkenes was reported, delivering the products functionalized at subterminal methylene and terminal methyl positions on an alkyl chain controlled by two different ligands, respectively, in good yields with to excellent site‐selectivities. The catalytic system showed functional group tolerance a broad substrate scope, including unactivated activated alkenes. More importantly, regioconvergent transformations mixtures isomeric were also successfully realized. results mechanistic studies demonstrate that reaction undergoes chain‐walking process give [Ar−Ir−H] complex alkene. subsequent processes proceed through modified Chalk–Harrod‐type mechanism via migratory insertion alkene into Ir−C bond followed C−H reductive elimination afford hydrofunctionalization site‐selectively.

Язык: Английский

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Nickel/SKP-Catalyzed Markovnikov Regio- and Enantioselective Hydroamination of Vinylarenes with Hydroxylamines

Organic Letters, Год журнала: 2023, Номер 25(35), С. 6577 - 6581

Опубликована: Авг. 30, 2023

A Ni-catalyzed enantioselective hydroamination of vinylarenes has been developed, affording a wide variety α-branched chiral alkylamines in good yields with exclusive Markovnikov regioselectivity and excellent enantioselectivity. The SKP ligand was found to be crucial both the reactivity enhancement enantiocontrol reaction. synthetic utility protocol exemplified gram-scale reaction late-stage modification medicinally relevant molecules. deuterium-labeling experiment revealed that irreversible hydronickelation is most likely enantioselectivity-determining step.

Язык: Английский

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Enhanced Enantioselective Discrimination Regulated by Achiral Ligands in Chiral Metal–Organic Frameworks

ACS Sensors, Год журнала: 2024, Номер 9(8), С. 4069 - 4078

Опубликована: Авг. 13, 2024

Enantioselective recognition is a fundamental property of chiral linkers in metal-organic frameworks (CMOFs). However, clarifying the efficient enantioselective discrimination tailored by achiral remains challenging to explain mechanism and efficiency. Here, two CMOFs ([Zn

Язык: Английский

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