Metal-Free Amino(hetero)arylation and Aminosulfonylation of Alkenes Enabled by Photoinduced Energy Transfer

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(30), С. 16630 - 16641

Опубликована: Июль 24, 2023

β-(Hetero)arylethylamines are privileged structural motifs found in many high-value organic molecules, including pharmaceuticals and natural products. To construct these important molecular skeletons, previous methods mainly achieved by amino(hetero)arylation reaction with the aid of transition metals preactivated substrates. Herein, we report a metal-free photoinduced intermolecular for single-step installation both (hetero)aryl iminyl groups across alkenes an efficient regioselective manner. This method shows broad scope (up to 124 examples) excellent tolerance various olefins─from simplest ethylene complex multisubstituted can all participate reaction. Furthermore, aminosulfonylation be also conducted presence sodium bisulfite as SO2 source.

Язык: Английский

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Difunctionalization Processes Enabled by Hexafluoroisopropanol

ACS Organic & Inorganic Au, Год журнала: 2024, Номер 4(3), С. 287 - 300

Опубликована: Март 4, 2024

In the past 5 years, hexafluoroisopropanol (HFIP) has been used as a unique solvent or additive to enable challenging transformations through substrate activation and stabilization of reactive intermediates. this Review, we aim at describing difunctionalization processes which were unlocked when HFIP was involved. Specifically, focus on cyclizations additions alkenes, alkynes, epoxides, carbonyls that introduce wide range functional groups interest.

Язык: Английский

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Modular and Practical 1,2‐Aryl(Alkenyl) Heteroatom Functionalization of Alkenes through Iron/Photoredox Dual Catalysis**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(44)

Опубликована: Сен. 13, 2023

Abstract Efficient methods for synthesizing 1,2‐aryl(alkenyl) heteroatomic cores, encompassing heteroatoms such as nitrogen, oxygen, sulfur, and halogens, are of significant importance in medicinal chemistry pharmaceutical research. In this study, we present a mild, versatile practical photoredox/iron dual catalytic system that enables access to highly privileged pharmacophores with exceptional efficiency site selectivity. Our approach exhibits an extensive scope, allowing the direct utilization wide range commodity or commercially available (hetero)arenes well activated unactivated alkenes diverse functional groups, drug scaffolds, natural product motifs substrates. By merging iron catalysis photoredox cycle, vast array alkene functionalization products incorporate neighboring azido, amino, halo, thiocyano nitrooxy group were secured. The scalability ability rapid synthesize numerous bioactive small molecules from readily starting materials highlight utility protocol.

Язык: Английский

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Stereospecific Synthesis of Unprotected, α,β-Disubstituted Tryptamines and Phenethylamines from 1,2-Disubstituted Alkenes via a One-Pot Reaction Sequence

Organic Letters, Год журнала: 2023, Номер 25(20), С. 3654 - 3658

Опубликована: Май 12, 2023

Unprotected, α,β-disubstituted tryptamines and phenethylamines are obtained by a one-pot, metal-free sequence that proceeds the in situ formation of aziridinium salts followed Friedel–Crafts reaction with electron-rich (hetero)arenes. Both steps facilitated hexafluoroisopropanol as solvent. The one-pot was effective for diversely substituted indoles 1,3,5-trimethoxybenzene, cyclic acyclic alkenes, proceeded stereospecific fashion both (E)- (Z)-1,2-disubstituted alkenes. Moreover, morpholine addition to an salt provided diamine.

Язык: Английский

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Catalytic Synthesis of β‐(Hetero)arylethylamines: Modern Strategies and Advances

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

Опубликована: Авг. 21, 2023

Abstract β‐(Hetero)arylethylamines appear in a myriad of pharmaceuticals due to their broad spectrum biological properties, making them prime candidates for drug discovery. Conventional methods preparation often require engineered substrates that limit the flexibility synthetic routes and diversity compounds can be accessed. Consequently, provide rapid versatile access those scaffolds remain limited. To overcome these challenges, chemists have designed innovative modular strategies β‐(hetero)arylethylamine motif, paving way more extensive use future pharmaceuticals. This review outlines recent progresses synthesis (hetero)arylethylamines emphasizes how innovations enabled new levels molecular complexity, selectivity, practicality.

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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Rh(III)-Catalyzed Diastereo- and Enantioselective Regiodivergent (Hetero)Arylamidation of (Homo)Allylic Sulfides

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(14), С. 9768 - 9778

Опубликована: Март 28, 2024

A rhodium-catalyzed 3-component conjunctive diastereo- and regioselective arylamidation of (homo)allylic sulfides, organon boronic acids, dioxazolones is reported. These reactions deliver the 1,2-insertion 2,1-insertion products, respectively, for allylic sulfides homoallylic sulfides. The enantioselective terminal internal achieved, furnishing various 1,3-N,S compounds featuring one or two contiguous stereocenters in high yields with enantioselectivities. Mechanistic studies suggest a change turnover-limiting selectivity-determining steps induced by native easily removable sulfide group.

Язык: Английский

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Electrochemically‐Driven 1,4‐Aryl Migration via Radical Fluoromethylation of N‐Allylbenzamides: a Straightforward Access to Functionalized β‐Arylethylamines

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(29)

Опубликована: Апрель 30, 2024

An electrochemical radical Truce Smiles rearrangement of N-allylbenzamides is documented herein. The selective 1,4-aryl migration was triggered by the fluoromethylation alkene providing a direct route to fluoro derivatives highly privileged β-arylethylamine pharmacophore. This practical transformation utilizes readily available starting materials and employs an electrical current drive oxidative process under mild reaction conditions. It accommodates variety migratory aryl groups with different electronic properties substitution patterns. Careful selection protecting group on nitrogen atom N-allylbenzamide crucial outcompete undesired 6-endo cyclization achieve high level selectivity towards migration. DFT calculations support mechanism unveil origin between two competitive pathways.

Язык: Английский

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Harnessing Bromo/Acyloxy Transposition (BrAcT) and Excited-State Copper Catalysis for Styrene Difunctionalization

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(31), С. 21271 - 21279

Опубликована: Июль 23, 2024

1,2-Difunctionalization of styrenes, adding two distinct functional groups across the C═C double bond, has emerged as a powerful tool for enhancing molecular complexity. Herein, we report development regioconvergent β-acyloxylation-α-ketonylation styrenes through bromo/acyloxy transposition (BrAcT) and excited-state copper catalysis. This approach is amenable to gram-scale synthesis tolerates wide range complex frameworks, including derivatives natural products marketed drugs. Our experimental computational studies suggest unique mechanism featuring dynamic, ionic BrAcT process copper-catalyzed redox reactions. We anticipate that this could serve broadly applicable versatile strategy β-acyloxylation-α-functionalization creating valuable intermediates preparing new pharmaceuticals, agrochemicals, materials.

Язык: Английский

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