Enantioselective Reductive Cross-Couplings of Olefins by Merging Electrochemistry with Nickel Catalysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(44), С. 23910 - 23917

Опубликована: Окт. 26, 2023

The merger of electrochemistry and transition metal catalysis has emerged as a powerful tool to join two electrophiles in an enantioselective manner. However, the development electroreductive cross-couplings olefins remains challenge. Inspired by advantages synergistic use with nickel catalysis, we present here Ni-catalyzed cross-coupling acrylates aryl halides alkyl bromides, which affords chiral α-aryl carbonyls good excellent enantioselectivity. Additionally, this catalytic reaction can be applied (hetero)aryl chlorides, is difficult achieve other methods. combination cyclic voltammetry analysis electrode potential studies suggests that NiI species activates oxidative addition bromides single-electron transfer.

Язык: Английский

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Ligand-Controlled, Nickel-Catalyzed Stereodivergent Construction of 1,3-Nonadjacent Stereocenters

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(22), С. 15453 - 15463

Опубликована: Май 25, 2024

In contrast to the asymmetric synthesis of molecules with a single stereocenter or 1,2-adjacent stereocenters, simultaneous construction acyclic 1,3-nonadjacent stereocenters via catalyst in an enantioselective and diastereoselective manner remains formidable challenge. Here, we demonstrate diastereodivergent through Ni-catalyzed reductive cyclization/cross-coupling alkene-tethered aryl bromides α-bromoamides, which represents major remaining stereochemical challenge cyclization/difunctionalization alkenes. Using Ming-Phos as ligand, diverse set oxindoles containing were obtained high levels enantio- diastereoselectivity. Mechanistic experiments density functional theory calculations indicate that magnesium salt plays key role controlling Furthermore, another complementary stereoisomeric products constructed from same starting materials using Ph-Phox ligand.

Язык: Английский

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Enantioselective Directed Nickel-Catalyzed Three-Component Reductive Arylalkylation of Alkenes via the Carbometalation/Radical Cross-Coupling Sequence

ACS Catalysis, Год журнала: 2024, Номер 14(7), С. 4395 - 4406

Опубликована: Март 8, 2024

Asymmetric reductive three-component arylalkylation of alkenes via the radical relay method has been well established, while asymmetric migratory insertion strategy remains unexplored. We report enantioselective nickel-catalyzed cross-electrophile with aryl- and alkyl halides an integrated Heck carbometalation/radical cross-coupling sequence. This protocol employing a chiral Ni/PHOX catalytic system allows terminal internal to successfully engage exquisite control regio-, chemo-, stereoselectivity. More importantly, this undergoes regio- arylnickelation followed by Csp3–Csp3 elimination, thus exhibiting reverse regioselectivity method. Mild reaction conditions exceptional functional group tolerance facilitate method's compatibility bioactive motifs modular synthesis biologically active compounds. The experiments density theory calculations provide insights into mechanism origin stereoselectivity, hemilabile nature PHOX ligand is critical for achieving arylalkylation.

Язык: Английский

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Palladium-Catalyzed Enantioselective Multicomponent Cross-Coupling of Trisubstituted Olefins

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(24), С. 16892 - 16901

Опубликована: Июнь 6, 2024

The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as straightforward and efficient tool stereoselectively forging C–C bond. Nevertheless, the creation acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within domain chemistry despite their prominence various bioactive small molecules. Herein, we describe palladium-catalyzed asymmetric multicomponent trisubstituted alkene with aryl diazonium salts arylboronic acids to realize tertiary-quaternary centers high regio-, distereo-, enantioselectivity. Specifically, precise manipulation stereoconfiguration alkenes enables divergent stereoselective reaction, thus allowing facile construction all four enantiomers. Harnessing ligand-swap strategy involving chiral bisoxazoline an achiral fumarate individually accelerates enantioselective migratory insertion reductive elimination step process, supported by density functional theory (DFT) calculations, obviating requirement neighboring directing group internal olefin skeleton.

Язык: Английский

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Three-component dicarbofunctionalization of allylamines via nucleopalladation pathway: unlocking vicinal and geminal selectivity

Chemical Science, Год журнала: 2024, Номер 15(13), С. 4890 - 4896

Опубликована: Янв. 1, 2024

A palladium( ii )-catalyzed vicinal and geminal selective dicarbofunctionalization of allylamine embedded in a removable picolinamide auxiliary is developed by exploiting nucleopalladation-triggered intermolecular three-component coupling reaction.

Язык: Английский

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Enantioselective Synthesis of P-Chiral Phosphine Oxides Bearing an All-Carbon Quaternary Stereogenic Center via Palladium-Catalyzed Domino Heck–Suzuki Reaction

ACS Catalysis, Год журнала: 2024, Номер unknown, С. 14762 - 14768

Опубликована: Сен. 20, 2024

Язык: Английский

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Pd/Cu-Cocatalyzed Enantio- and Diastereodivergent Wacker-Type Dicarbofunctionalization of Unactivated Alkenes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(38), С. 26121 - 26130

Опубликована: Авг. 5, 2024

The Wacker and Wacker-type reactions are some of the most fundamental powerful transformations in organic chemistry for their ability to efficiently produce valuable chemicals. Remarkable progress has been achieved asymmetric oxy/aza-Wacker-type reactions; however, dicarbofunctionalization remains underdeveloped, especially concurrent construction two stereocenters. Herein, we report a Pd/Cu-cocatalyzed enantio- diastereodivergent alkene-tethered aryl triflates with imino esters. A series 2-indanyl motifs bearing adjacent carbon stereocenters could be easily synthesized moderate excellent yields good diastereo- enantioselectivities (up >20:1 dr >99% ee). Density functional theory calculations revealed that origin diastereoselectivity this Pd/Cu synergistic catalytic system is jointly determined by both intermolecular anti-carbopalladation alkenes reductive elimination processes, accordance Curtin–Hammett principle.

Язык: Английский

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Photocatalyzed Azidofunctionalization of Alkenes via Radical‐Polar Crossover

Angewandte Chemie International Edition, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

The azidofunctionalization of alkenes under mild conditions using commercially available starting materials and easily accessible reagents is reported based on a radical-polar crossover strategy. A broad range alkenes, including vinyl arenes, enamides, enol ethers, sulfides, dehydroamino esters, were regioselectively functionalized with an azide nucleophiles such as azoles, carboxylic acids, alcohols, phosphoric oximes, phenols. method led to more efficient synthesis 1,2-azidofunctionalized pharmaceutical intermediates when compared previous approaches, resulting in both reduction step count increase overall yield. scope limitations these transformations further investigated through standard unbiased selection 15 substrate combinations out 1,175,658 possible clustering technique.

Язык: Английский

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Photocatalyzed Azidofunctionalization of Alkenes via Radical‐Polar Crossover

Angewandte Chemie, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Abstract The azidofunctionalization of alkenes under mild conditions using commercially available starting materials and easily accessible reagents is reported based on a radical‐polar crossover strategy. A broad range alkenes, including vinyl arenes, enamides, enol ethers, sulfides, dehydroamino esters, were regioselectively functionalized with an azide nucleophiles such as azoles, carboxylic acids, alcohols, phosphoric oximes, phenols. method led to more efficient synthesis 1,2‐azidofunctionalized pharmaceutical intermediates when compared previous approaches, resulting in both reduction step count increase overall yield. scope limitations these transformations further investigated through standard unbiased selection 15 substrate combinations out 1,175,658 possible clustering technique.

Язык: Английский

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Copper-Catalyzed Enantioselective Three-Component Fluoroalkylalkynylation of Unactivated Alkenes

ACS Catalysis, Год журнала: 2025, Номер 15(3), С. 1693 - 1703

Опубликована: Янв. 16, 2025

The enantioselective three-component dicarbonfunctionalization of electronically unactivated alkenes continues to pose a significant challenge. In this work, copper-catalyzed highly regio- and fluoroalkylalkynylation with diverse terminal alkynes fluoroalkyl halides under mild conditions is developed. addition halides, Togni's reagent can also participate in the reaction, delivering chiral β-trifluoromethyl high enantioselectivities. This method exhibits good functional group tolerance, facilitating late-stage derivatization variety biologically active molecules. success chemistry was achieved by using bulky indene-substituted BOPA ligand. DFT calculations indicate that radical through fluorine-directed outer-sphere pathway. Mechanistic studies reveal amide crucial for achieving stereoselectivities because exclusive F···H hydrogen bonding between Mes on be formed stabilize Si-radical coupling transition state.

Язык: Английский

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