Nickel-Catalyzed Regio- and Enantioselective Borylative Coupling of Terminal Alkenes with Alkyl Halides Enabled by an Anionic Bisoxazoline Ligand

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(25), P. 13603 - 13614

Published: June 6, 2023

Chiral boronic esters are a class of versatile building blocks. We describe herein an asymmetric nickel-catalyzed borylative coupling terminal alkenes with nonactivated alkyl halides. The success this reaction is ascribed to the application chiral anionic bisoxazoline ligand. This study provides three-component strategy access α- and β-stereogenic from easily accessible starting materials. protocol characterized by mild conditions, wide substrate scope high regio- enantioselectivity. also showcase value method in simplifying synthesis several drug molecules. Mechanistic studies suggest that generation enantioenriched bearing α-stereogenic center results stereoconvergent process, while enantioselectivity-controlling step β-stereocenter switched olefin migratory insertion due coordination ester group.

Language: Английский

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Coordination Assistance: A Powerful Strategy for Metal-Catalyzed Regio- and Enantioselective Hydroalkynylation of Internal Alkenes

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(3), P. 308 - 321

Published: Jan. 11, 2023

ConspectusAlkenes are versatile compounds that readily available on a large scale from industry or through organic synthesis. The widespread occurrence of alkenes provides the continuous impetus for development catalytic asymmetric alkene hydrofunctionalizations, which enables expeditious construction complex chiral molecules starting materials. Catalytic hydrofunctionalization internal presents notable challenge, due to their low reactivity, many potential side reactions, and simultaneous control regio-, diastereo-, enantioselectivities.Dehydroamino acids enamides among first substrates provide enantioselectivities in hydrogenation. crucial importance an amide coordinating group is established by series classical mechanistic studies. This initial success greatly stimulated further hydrogenation hydrofunctionalization. Building these pioneering works as well related we have adopted coordination assistance powerful tool address challenges associated with alkenes. Using functional substrate native group, two-point binding mode metal center effectively enhances reactivity facilitates diastereo- enantioselectivities. Through this strategy, developed number methods excellent enantiocontrols.In Account, summarize recent advance our lab using key element achieve regio- enantioselective hydroalkynylation First, describe early work aimed at controlling enantioselectivity disubstituted enamide substrate. Both α- β-alkynylation were achieved channeling reaction pathway into Chalk-Harrod modified mechanism. Next, discuss catalysts regiodivergent trisubstituted access vicinal stereocenters quaternary carbon stereocenters. We also α,β-unsaturated amides unconventional site-selectivity combination isomerization regioselective hydroalkynylation. basis remote stereocenter β,γ-unsaturated amides. show principle applicable terminal well. A ligand-controlled mechanism shift discussed alkynylation position 1,1,-disubstituted Finally, briefly mention application other hydrofunctionalizations such hydroboration hydrosilylation, where previously inaccessible selectivity achieved. Collectively, demonstrate power hydrofunctionalizations. anticipate strategy will create platform enable diverse transformations.

Language: Английский

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Diversified Synthesis of Chiral Fluorinated Cyclobutane Derivatives Enabled by Regio‐ and Enantioselective Hydroboration

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(23)

Published: April 2, 2024

The diversified synthesis of chiral fluorinated cyclobutane derivatives has remained a difficult task in synthetic chemistry. Herein, we present an approach for asymmetric hydroboration and formal hydrodefluorination gem-difluorinated cyclobutenes through rhodium catalysis, providing α-boryl cyclobutanes monofluorinated with excellent regio- enantioselectivity, respectively. key to the success two transformations relies on efficient, mild highly selective rhodium-catalyzed HBPin (pinacolborane), which subsequent addition base, catalytic amount palladium some cases, results formation products four-membered ring retained. obtained are versatile building blocks that provide platform enantioenriched great diversity.

Language: Английский

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Directing Group Repositioning Strategy Enabled Site- and Enantioselective Addition of Heteroaromatic C–H Bonds to Acyclic Internal Alkenes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(12), P. 6861 - 6870

Published: March 14, 2023

Despite the notable advances achieved in Murai-type hydroarylations, highly enantioselective catalytic addition of native (hetero)arenes to internal alkenes remains a prominent challenge. Herein, we report directing group repositioning strategy, which enables iridium-catalyzed heteroarenes including furan, benzofuran, and thiophene enamides. The C-H bond at C2 position heteroarene is site-selectively cleaved added regioselectively β-position an enamide, affording valuable β-heteroaryl amide with high enantioselectivity. Mechanistic studies indicate that rate enantioselectivity are determined by separate elementary steps.

Language: Английский

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The current utility and future potential of multiborylated alkanes

Nature Reviews Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Language: Английский

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Amide-Directed, Rhodium-Catalyzed Enantioselective Hydrosilylation of Unactivated Internal Alkenes

Organic Letters, Journal Year: 2023, Volume and Issue: 25(10), P. 1667 - 1672

Published: March 9, 2023

Despite the recent advances made in area of asymmetric hydrosilylation, metal-catalyzed enantioselective hydrosilylation unactivated internal alkenes remains a challenge. Here, we report rhodium-catalyzed bearing polar group. The coordination assistance by an amide group enables to occur with high regio- and enantioselectivity.

Language: Английский

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Rhodium-Catalyzed Double Hydroboration of Quinolines

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(10), P. 7067 - 7078

Published: May 9, 2023

Selective double hydroelementation of N-heteroarenes can be one the most straightforward and atom-economic routes toward dearomatized N-heterocycles bearing a (chiral) sp3 C–E bond (E = B, Si, etc.) at specific site. Herein, we describe development one-pot, site- stereoselective borylative reduction quinolines leading to series tetrahydroquinolines that possess an (enantioenriched) C(sp3)–B in 4-position. A cationic Rh precatalyst [Rh(cod)2]OTf with phosphine ligand DPEPhos enabled range HBpin provide C4-borylated (THQ) good high yields under mild conditions. Mechanistic studies elucidated Rh-mediated stepwise dearomative cascade: (i) moderately regioselective hydroboration quinoline resulting mixture 1,2- 1,4-dihydroquinolines (DHQ), (ii) 1,2-DHQ intermediate give THQ, (iii) slow isomerization 1,4-DHQ 1,2-DHQ, (iv) formation Rh-quinoline adduct as catalytic resting species. The C4-selective asymmetric within Rh/(S)-BINAP system was accomplished albeit moderate enantioselectivity on average yields. installed C(sp3)–Bpin unit 4-position transformed various functional groups through simple organic reactions.

Language: Английский

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Fe-Catalyzed C(sp³)–H Diversification toward γ-Functionalized Amides via Iron Nitrenoid: Mechanistic Insights and Applications

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(21), P. 14023 - 14030

Published: Oct. 18, 2023

Access to γ-functionalized amides represents a challenge in organic synthesis. The recent upsurge of biomimetic metal nitrenoid-mediated C–H functionalization offers method for producing N-containing molecules. Here, we describe an iron-catalyzed γ-C(sp3)–H diversification dioxazolones access amides. activation step proceeds via the formation iron nitrenoid species, followed by 1,5-hydrogen atom transfer (1,5-HAT). A crucial dihydrofuranimine species is isolated and characterized. This intermediate undergoes nucleophilic substitution furnish desired product through SN2 mechanism. reaction obviates need external chemical oxidants exhibits compatibility with electron-rich substrates various nitrogen, oxygen, carbon nucleophiles. catalyst also up 9500 turnovers on complex natural products, emphasizing its utility synthesis drug development.

Language: Английский

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Direct Synthesis of β-Amino Boronates via Amide α-C–H Bond Activation and C(sp³)–C(sp³) Coupling under Dual Ni/Photoredox Catalysis

ACS Catalysis, Journal Year: 2023, Volume and Issue: 14(1), P. 547 - 553

Published: Dec. 26, 2023

Direct transformations of readily available amines or amides via C–H bond functionalization could provide a fast route for accessing complex molecules. While various groups have been successfully incorporated into the α position nitrogen atom with photoredox system activation, couplings functionalized alkyl halides are still very challenging. Herein, we report direct and convenient protocol β-amino boronates through C(sp3)–C(sp3) coupling α-bromoboronates. The mild conditions allow good functional group tolerance broad scope. application method in late-stage modification molecules further demonstrates its great potential organic synthesis. Mechanistic studies were also conducted, catalytic cycle is proposed.

Language: Английский

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Ligand-Controlled Enantioselective Copper-Catalyzed Hydroboration and Ring-Opening Dihydroboration of Arylidenecyclobutanes

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Arylidenecyclobutanes are readily accessible and versatile reagents in synthetic chemistry due to the multifaceted reactivity exhibited by their alkene strained cyclobutane moieties. However, metal-catalyzed enantioselective functionalization of arylidenecyclobutanes, particularly controllable ring-retaining ring-opening reactions, is rarely explored. Considering utility enantioenriched organoboronate compounds, herein we report ligand-controlled copper-catalyzed hydroboration dihydroboration reactions arylidenecyclobutanes that afford chiral α-cyclobutyl benzylboronate 1,5-diboronate compounds with high enantioselectivity when (S)-DTBM-Segphos (S,S)-Ph-BPE employed, respectively. Mechanistic studies reveal process via β-C elimination significantly slower than arylidenecyclopropanes presence CuOAc (S,S)-Ph-BPE. The these two protocols further demonstrated through conducting various stereospecific site-selective transformations organoboron products, including concise synthesis bioactive molecules.

Language: Английский

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