Nickel-Catalyzed Enantioselective C(sp³)–C(sp³) Cross-Electrophile Coupling of N-Sulfonyl Styrenyl Aziridines with Alkyl Bromides

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(37), P. 25426 - 25432

Published: Sept. 4, 2024

Herein, we report the first example of a highly enantioselective alkylative aziridine ring opening. Under catalysis chiral nickel/pyridine-imidazoline complex, asymmetric C(sp

Language: Английский

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Dynamic Kinetic Activation of Aziridines Enables Radical-Polar Crossover (4 + 3) Cycloaddition with 1,3-Dienes

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

Published: Jan. 10, 2025

The cycloaddition of aziridines with unsaturated compounds is a valuable method for synthesizing nitrogen heterocycles. However, this process predominantly substrate-controlled, posing significant challenges in regulating the regioselectivity C–N bond cleavage. In study, we report nickel-catalyzed dynamic kinetic activation strategy that enables catalyst-controlled aziridines. Various types aziridines, including 2-phenyl, 2-carbonyl, 2-alkyl, and disubstituted consistently cleave their more sterically hindered bonds to generate 1,3-radical anion intermediates. These intermediates participate highly regioselective 1,4-Heck/allylic substitution cascade aromatic branched 1,3-dienes, resulting radical-polar crossover (4 + 3) produces seven-membered azepine products. This approach not only complements traditional dipolar cycloaddition, which typically act as zwitterionic 1,3-dipoles, but also introduces an unusual mode 1,3-dienes. Experimental investigations density functional theory (DFT) calculations provide insight into reaction mechanism.

Language: Английский

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Nickel-Catalyzed Rearranged Alkenylation of 2-Arylaziridines with Aryl Alkenes to Access Allylamines

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

The transition-metal-catalyzed ring-opening functionalization of aziridines presents a promising approach for synthesizing structurally complex amines. However, the rearranged poses significant challenges. Herein, we report first alkenylation with aryl alkenes via Ni-Brønsted acid co-catalysis, leading to rapid synthesis diverse array allylamines yields reaching up 91%. Mechanistic studies suggest that reaction occurs through rearrangement aziridine generate an imine intermediate. This intermediate is subsequently captured by alkene under nickel catalysis, ultimately formation allylamines.

Language: Английский

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From Quaternary Carbon to Tertiary C(sp³)–Si and C(sp³)–Ge Bonds: Decyanative Coupling of Malononitriles with Chlorosilanes and Chlorogermanes Enabled by Ni/Ti Dual Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(21), P. 14445 - 14452

Published: May 13, 2024

Transition-metal-catalyzed C–Si/Ge cross-coupling offers promising avenues for the synthesis of organosilanes/organogermanes, yet it is fraught with long-standing challenges. A Ni/Ti-catalyzed strategy reported here, allowing use disubstituted malononitriles as tertiary C(sp3) coupling partners to couple chlorosilanes and chlorogermanes, respectively. This method enables catalytic cleavage C(sp3)–CN bond quaternary carbon followed by formation C(sp3)–Si/C(sp3)–Ge bonds from ubiquitously available starting materials. The efficiency generality are showcased a broad scope both partners, therefore holding potential synthesize structurally diverse organosilanes organogermanes that were difficult access previously.

Language: Английский

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Selective C–N Bond Cleavage in Unstrained Pyrrolidines Enabled by Lewis Acid and Photoredox Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 23, 2024

Cleavage of inert C-N bonds in unstrained azacycles such as pyrrolidine remains a formidable challenge synthetic chemistry. To address this, we introduce an effective strategy for the reductive cleavage bond

Language: Английский

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Nickel-catalysed chelation-assisted reductive defluorinative sulfenylation of trifluoropropionic acid derivatives

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(17), P. 2405 - 2408

Published: Jan. 1, 2024

Nickel-catalysed chelation-assisted reductive cross-coupling of trifluoropropanamides/esters with disulfides to afford thioacrylamides/esters high E selectivity, involving triple C–F bond cleavage.

Language: Английский

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Photocatalyzed Azidofunctionalization of Alkenes via Radical‐Polar Crossover

Angewandte Chemie International Edition, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

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Photocatalyzed Azidofunctionalization of Alkenes via Radical‐Polar Crossover

Angewandte Chemie, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

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Recent Advances in Single-Electron Reduction-Induced Ring Opening of N-Acyl Cyclic Amines

Synthesis, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Abstract Cyclic amines represent ubiquitous structural motifs in organic chemistry, prominently featured natural products and pharmaceuticals. The development of synthetic methodologies targeting cyclic has attracted considerable interest, given their significance medicinal chemistry. These transformations can be broadly categorized into two main types: (1) peripheral modification (2) skeletal remodeling. Recent advancements late-stage C–H functionalization have showcased the potential strategies. Conversely, remodeling, particularly through ring opening amines, emerged as a powerful approach to access structurally diverse amines. Ring initiated by C–N bond cleavage, predominantly relies on two-electron mechanisms. Strained readily undergo such transformations, while those with larger-membered ring, like pyrrolidines, present greater challenges. Oxidative von Braun-type approaches facilitated heterolytic offering broad applicability across various In contrast, reductive approaches, which enable homolytic provide unique radical-mediated transformations. This short review highlights recent progress single electron reduction induced ring-opening methodologies, focusing α-aminoketyl radical generation for selective amide cleavage. Advances aziridines, azetidines, other are discussed, along implications future prospects. 1 Introduction 2 Opening Aziridines 2.1 Hydrogenation Alkylation 2.2 Isomerization 2.3 Arylation 3 Azetidines 4 Pyrrolidines Other Amines 5 Conclusion Outlook

Language: Английский

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Revealing the Relationship between Publication Bias and Chemical Reactivity with Contrastive Learning

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

Published: March 2, 2025

A synthetic method's substrate tolerance and generality are often showcased in a "substrate scope" table. However, selection exhibits frequently discussed publication bias: unsuccessful experiments or low-yielding results rarely reported. In this work, we explore more deeply the relationship between such bias chemical reactivity beyond simple analysis of yield distributions using novel neural network training strategy, scope contrastive learning. By treating reported substrates as positive samples nonreported negative samples, our learning strategy teaches model to group molecules within numerical embedding space, based on historical trends published tables. Training 20,798 aryl halides CAS Content CollectionTM, spanning thousands publications from 2010 2015, demonstrate that learned embeddings exhibit correlation with physical organic descriptors through both intuitive visualizations quantitative regression analyses. Additionally, these applicable various reaction modeling tasks like prediction regioselectivity prediction, underscoring potential use data pretraining task. This work not only presents chemistry-specific machine learn literature new way but also represents unique approach uncover reflected by publications.

Language: Английский

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