Studies on the Origin of the Stabilizing Effects of Fluorinated Alcohols and Weakly Coordinated Fluorine-Containing Anions on Cationic Reaction Intermediates

The Journal of Organic Chemistry, Год журнала: 2022, Номер 87(3), С. 1814 - 1829

Опубликована: Янв. 12, 2022

Many synthetic methods that use fluorinated alcohols as solvents have been reported, and the found to be crucial success of these methods. In addition, there reports indicating adding a weakly coordinated fluorine-containing anion, such BF4-, PF6-, or SbF6-, can improve yields. The boosting effect is attributed mainly hydrogen bond activation. A few studies suggested very polar stabilize cationic reaction intermediates. However, how they do so why anions yields not studied in depth. Here, we used quaternary ammonium cations, phosphonium cation, triaryl-substituted carbocation models for short-lived intermediates possible interactions cations with SbF6-. On basis results, propose C-F dipoles E-F (where E B, P, Sb) stabilized by intermolecular charge-dipole interactions. We deduced same fashion thermodynamically

Язык: Английский

---

Intramolecular chaperone-assisted dual-anchoring activation (ICDA): a suitable preorganization for electrophilic halocyclization

Chemical Science, Год журнала: 2024, Номер 15(16), С. 6130 - 6140

Опубликована: Янв. 1, 2024

The halocyclization reaction represents one of the most common methodologies for synthesis heterocyclic molecules. Many efforts have been made to balance relationship between structure, reactivity and selectivity, including design new electrophilic halogenation reagents utilization activating strategies. However, discovering universal or strategies remains challenging due case-by-case practice different substrates cyclization models. Here we report an intramolecular chaperone-assisted dual-anchoring activation (ICDA) model halocyclization, taking advantage non-covalent orientation as driving force. This protocol allows a practical, catalyst-free rapid approach access seven types small-sized, medium-sized, large-sized units realize polyene-like domino halocyclizations, exemplified by nearly 90 examples, risk-reducing flow gram-scale synthesis. DFT studies verify crucial role ICDA in affording suitable preorganization transition state stabilization X

Язык: Английский

---

HFIP-catalyzed highly diastereoselective formal [4 + 2] cyclization to synthesize difluorinated multisubstituted chromans using difluoroenoxysilanes as C2 synthons

Chinese Chemical Letters, Год журнала: 2021, Номер 33(6), С. 3007 - 3011

Опубликована: Дек. 6, 2021

Язык: Английский

---

Cycloisomerization of Carbamoyl Chlorides in Hexafluoroisopropanol: Stereoselective Synthesis of Chlorinated Methylene Oxindoles and Quinolinones

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(34), С. 18478 - 18483

Опубликована: Июнь 22, 2021

Abstract Hexafluoroisopropanol (HFIP) was employed as an additive for the generation of 3‐(chloromethylene)oxindoles via chloroacylation alkyne‐tethered carbamoyl chlorides. This reaction avoids use a metal catalyst and accesses products in high yields stereoselectivities. Additionally, this is scalable proved amenable to series product derivatizations, including synthesis nintedanib. The reactivity alkene‐tethered chlorides with hexafluoroisopropanol harnessed towards 2‐quinolinones.

Язык: Английский

---

Transition-Metal-Free Regioselective Intermolecular Hydroamination of Conjugated 1,3-Dienes with Heterocyclic Amines

Organic Letters, Год журнала: 2022, Номер 24(12), С. 2452 - 2456

Опубликована: Март 17, 2022

The unique property of hexafluoroisopropanol (HFIP) enables the regioselective hydroamination 1,3-dienes with nitrogen heterocycles in a Markovnikov manner presence catalytic Brønsted acid. This transition-metal-free intermolecular protocol is achieved under mild reaction conditions. aggregation by HFIP and acid helps to activate terminal double bond regioselectively. Following protonation diene, C-N formation accomplished upon involvement heterocyclic amines.

Язык: Английский

---

Manganese‐Catalyzed Anti‐Markovnikov Hydroarylation of Enamides: Modular Synthesis of Arylethylamines

Chinese Journal of Chemistry, Год журнала: 2022, Номер 40(13), С. 1546 - 1552

Опубликована: Апрель 19, 2022

Comprehensive Summary The arylethylamine framework is a prevalent motif in great range of biologically important organic compounds. One intractable task for frontline drug discovery to find structurally new medicine candidates instead opioid, based on the construction rich chemical space motif. In this report, practical protocol synthesis functionality common pharmaceutical chemicals has been developed. It proceeds by Mn‐catalyzed anti‐Markovnikov hydroarylation electron‐rich enamides under mild conditions without use ligands. spite mismatched electronic effects during manganese‐mediated migratory insertion process, both terminal and internal can be regioselectively hydroarylated with various aryl boronic acids 15 min. Also, successful hydroalkenylation alkenyl air atmosphere affords an elegant route synthetically useful β ‐alkenylated amines satisfactory yields. synthetic robustness practicality reaction reveal its simple operation, short time, viability gram‐scale value late‐stage modification complex molecules.

Язык: Английский

---

Regio- and Stereoselective Allylation of Anilines with Aryl Allenes in Hexafluoroisopropanol Solvent

Organic Letters, Год журнала: 2023, Номер 25(27), С. 5073 - 5077

Опубликована: Июнь 30, 2023

A regio- and stereoselective allylation of N-unsubstituted anilines has been developed that explores aryl allenes as masked allyl synthons a combination Mg(OTf)2/HFIP an effective proton source. The protocol is operationally simple scalable offers high yields diverse p-allyl bearing olefin motif with exclusive E-geometry. methodology was also suitable for the regioselective indole can be advanced in three-component reaction mode using NIS activator. alteration catalytic system TfOH resulted difunctionalization allenes, which follows allylation/hydroarylation cascade.

Язык: Английский

---

HFIP-Promoted Aromatic Electrophilic Amidation of Indoles and Pyrroles with Isocyanates

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

A mild and practical method for synthesizing amidoindoles amidopyrroles was described via the direct amidation of indoles or pyrroles with isocyanates promoted by 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). In this reaction, HFIP acted as a strong hydrogen bond-donating solvent to activate isocyanates, enabling electron-rich nitrogen-containing heterocycles.

Язык: Английский

---

Chiral Bifunctional Selenide Catalysts for Asymmetric Iodolactonizations

Chemical and Pharmaceutical Bulletin, Год журнала: 2022, Номер 70(9), С. 599 - 604

Опубликована: Авг. 31, 2022

1,1′-Bi-2-naphthol (BINOL)-derived chiral bifunctional sulfide and selenide catalysts that possess a hydroxy group are known to be effective for enantioselective bromolactonizations. When applied asymmetric iodolactonizations of 4-pentenoic acids, these yield γ-butyrolactone products important compounds in medicinal chemistry. Although selenides have shown good catalytic performances iodolactonizations, reactions with BINOL-derived unexpectedly gave iodolactonization nearly racemic forms. The roles chalcogenide moieties groups on were investigated, the importance both moiety achieve was clarified. An optimized catalyst synthesis γ-butyrolactones phthalides. Furthermore, utility also demonstrated desymmetrizing α,α-diallyl carboxylic acids.

Язык: Английский

---

HFIP Mediates a Direct C−C Coupling between Michael Acceptors and Eschenmoser's salt

Angewandte Chemie International Edition, Год журнала: 2021, Номер 61(11)

Опубликована: Ноя. 23, 2021

Abstract A direct C−C coupling process that merges Michael acceptors and Eschenmoser's salt is presented. Although reminiscent of the Morita–Baylis–Hillman reaction, this requires no Lewis base catalyst. The underlying mechanism was unveiled by a combination kinetic, isotopic labelling experiments as well computational investigations, which showcased critical role HFIP superior mediator for proton‐transfer events decisive halide counterion.

Язык: Английский

---