Unraveling Alcohol Additive Effects on Hypervalent Iodine(III)-Catalyzed Asymmetric Phenolic Dearomatization: Ligand Substitution and Low-Barrier Hydrogen Bonds DOI
Hanliang Zheng, Cai Liu,

Xiaoyu Lai

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 15(1), P. 370 - 380

Published: Dec. 18, 2024

Despite the widespread use of hexafluoropropanol (HFIP) as a "magic" solvent or additive in organic synthesis, its fundamental mechanisms lag far behind. This study presents mechanistic insights into puzzling alcohol effects observed Ishihara's conformationally flexible C2-symmetric iodoarene-catalyzed asymmetric phenolic dearomatization through density functional theory calculations. The results reveal that due to "booster effect" fluorinated alcohols, HFIP assembles trimeric hydrogen bond cluster displaces ligand from active iodine(III) catalyst and forms low-barrier with substrate, which significantly enhances oxidizing power center, thus facilitating electron-deficient phenols. Conversely, methanol is found promote electron-rich phenols via formally similar yet distinct mechanism, highlighting unique role an additive. gained this investigation advance our molecular-level understanding synergistic interactions between catalysts additives, potentially guiding design catalytic systems exploit these for broader applications.

Language: Английский

Access to N-α-deuterated amino acids and DNA conjugates via Ca(II)-HFIP-mediated reductive deutero-amination of α-oxo-carbonyl compounds DOI Creative Commons
Haoran Li,

Yuwei Liu,

Silin Zhang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 20, 2025

The development of practical and selective strategies for deuterium incorporation to construct deuterated molecules, particularly deuterium-labeled amino acids, has become as a growing focus basic research, yet it remains formidable challenge. Herein, we present bioinspired calcium-HFIP-mediated site-selective reductive deutero-amination α-oxo-carbonyl compounds with amines. Utilizing d2-Hantzsch ester the source, this reaction attains remarkable deuteration efficiency (> 99% deuteration). It enables synthesis N-α-deuterated acid motifs wide range functionality, evidenced by over 130 examples. method exhibits compatibility diverse substrates, such peptides, drug natural products bearing different substituents. Moreover, application strategy in DNA-tagged acids/peptides been demonstrated. This work offers an efficient innovative solution chemistry holds substantial potential organic synthesis, medicinal chemistry, chemical biology.

Language: Английский

Citations

1
Controlling the regioselectivity of the bromolactonization reaction in HFIP DOI Creative Commons
Tuong Anh To, Nhu T. A. Phan, Binh Khanh

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(19), P. 7187 - 7197

Published: Jan. 1, 2024

The halolactonization reaction provides rapid access to densely functionalized lactones from unsaturated carboxylic acids. endo/exo regioselectivity of this cyclization is primarily determined by the electronic stabilization alkene substituents, thus making it inherently dependent on substrate structures. Therefore method often affords one type halolactone regioisomer only. Herein, we introduce a simple and efficient for regioselectivity-switchable bromolactonization reactions mediated HFIP solvent. Two sets conditions were developed, each forming endo-products or exo-products in excellent regioselectivity. A combination computational experimental mechanistic studies not only confirmed crucial role HFIP, but also revealed formation under kinetic control thermodynamic control. This study paves way future work use perfluorinated solvents dictate outcomes organic synthesis.

Language: Английский

Citations

7
Triflic Acid‐Catalyzed Dehydrative Amination of 2‐Arylethanols with Weak N‐Nucleophiles in Hexafluoroisopropanol DOI Creative Commons
Max Van Hoof, Robert J. Mayer, Joseph Moran

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Abstract The catalytic deoxyamination of readily available 2‐arylethanols offers an appealing, simple, and straightforward means accessing β‐(hetero)arylethylamines biological interest. Yet, it currently represents a great challenge to synthetic chemistry. In most cases, the alcohol has be either pre‐activated in situ or converted into reactive carbonyl intermediate, limiting substrate scope for some methods. Examples direct dehydrative amination are thus still scarce. Here, we describe protocol based on synergy triflic acid hexafluoroisopropanol, which enables stereospecific broad array 2‐arylethanols, does not require any pre‐activation alcohol. This approach yields high value‐added products incorporating sulfonamide, amide, urea, aniline functionalities. addition, this was applied sulfidation 2‐arylethanols. Mechanistic experiments DFT computations indicate formation phenonium ions as key intermediates reaction.

Language: Английский

Citations

5
EDA complexation of two donor molecules initiating radical cation cyclizations DOI

Julian C. G. Kürschner,

Martin Utikal,

Line Næsborg

et al.

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

Published: Jan. 16, 2025

Abstract In this study, a catalyst-free EDA complexation of two donor molecules using an acidic solvent is presented. The electron-rich aromatic compound (E)-anethole slowly protonated by the hexafluoroisopropanol (HFIP), leading to rapid formation photoactive complex between and another molecule. This resulting initiates radical chain cyclization reactions under green light irradiation.

Language: Английский

Citations

0
Iron N‐Doped Carbon Nanoarchitectonics for C─H Bond Activation of Methylarenes and Esterification Reactions DOI Creative Commons
Arun D. Kute, Hanumant B. Kale, Manoj B. Gawande

et al.

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

Published: March 16, 2025

Abstract Nowadays, selective oxidation of sp 3 C−H bond in methylarene to benzaldehyde under eco‐friendly conditions is a promising way produce aldehyde derivatives. In this work, scalable iron nanoparticles adorned on surface engineered nitrogen‐doped carbon (Fe NP @NC‐BA) fabricated via wet chemistry followed by high‐temperature pyrolysis. It observed that nitrogen‐coordinated Fe play crucial role as active sites facilitating both the toluene and esterification reaction due its nitrogen‐rich NPs contain low C/N ratio @NC‐BA catalyst. The @NC−BA catalyst N‐hydroxyphthalimide cooperatively converted methylarenes corresponding aryl aldehydes with 99% conversion selectivity, without over‐oxidation benzoic acid at room temperature. Further, EPR analysis used probe free radical pathway activation. Additionally, employed for microwave‐assisted acids alcohols leads selectivity. compatibility nanoarchitectonics highly efficient synthesis 24 derivatives 42 ester products. Furthermore, gram‐scale reusability study proved wide applicability Thus, decorated N‐doped catalysts provide durable, easily recoverable, environmentally friendly metal‐based reactions.

Language: Английский

Citations

0
Total synthesis of breviscapin B via intramolecular dehydrative etherification DOI
Kosho Makino,

Chiharu Nogami,

Shunsuke Sueki

et al.

Organic & Biomolecular Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The total synthesis of breviscapin B, a norlignan natural product having an unusual 2,2-diaryltetrahydrofuran skeleton, has been achieved via intramolecular dehydrative Williamson ether as key step.

Language: Английский

Citations

0
Syntheses of Unsymmetric (Sulfoxylidene)ureas from NH-Sulfoximines and Dioxazolones Assisted by 2,2,2-Trifluoroethanol DOI
Yijie Hu, Peng Wu, Chandan Chittapriya Sahu

et al.

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

Published: March 27, 2025

Ureas and sulfoximines are relevant as natural products pharmaceuticals. The fusion of these two frameworks results in (sulfoxylidene)ureas. Herein, we present a convenient method to access such compounds from NH-sulfoximines dioxazolones. reactions assisted by 2,2,2-trifluoroethanol (TFE), yielding the desired moderate good yields under mild reaction conditions. process, which involves Curtius rearrangement, is characterized its simplicity absence any additional activator rendering it appealing for applications medicinal chemistry.

Language: Английский

Citations

0
A Povarov-Type Reaction to Access Tetrahydroquinolines from N-Benzylhydroxylamines and Alkenes in HFIP DOI Creative Commons
Valentyn Pozhydaiev,

Daniella Al-Othman,

Joseph Moran

et al.

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(76), P. 10504 - 10507

Published: Jan. 1, 2024

Here, we report the synthesis of tetrahydroquinolines between newly developed

Language: Английский

Citations

2
Iron(II)‐Catalyzed 1,2‐Diamination of Styrenes Installing a Terminal NH2 Group Alongside Unprotected Amines DOI Creative Commons
Valentyn Pozhydaiev,

Antonio Paparesta,

Joseph Moran

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(45)

Published: July 17, 2024

1,2-Diamination of alkenes represents an attractive way to generate differentiated vicinal diamines, which are prevalent motifs in biologically active compounds and catalysts. However, existing methods usually limited scope produce diamines where one or both nitrogens protected, adding synthetic steps for deprotection further N-functionalization reach a desired target. Furthermore, the range amino groups that can be introduced at internal position is fairly limited. Here we describe 1,2-diamination styrenes directly installs free group terminal wide variety unprotected nitrogen nucleophiles (primary secondary alkyl aromatic amines, sulfoximines, N-heterocycles, ammonia surrogate) position. Two complementary sets conditions encompass electronically activated deactivated with diverse substitution patterns functional groups. Moreover, this strategy extended 1,2-aminothiolation styrenes.

Language: Английский

Citations

2
Regioselective fluorination of allenes enabled by I(I)/I(III) catalysis DOI Creative Commons
Zixuan Wang,

Yameng Xu,

Ryan Gilmour

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 9, 2024

Abstract The prominence and versatility of propargylic fluorides in medicinal chemistry, coupled with the potency F/H F/OH bioisosterism, has created a powerful impetus to develop efficient methods facilitate their construction. Motivated by well-established conversion alcohols allenes, an operationally simple, organocatalysis-based strategy process these abundant unsaturated precursors would be highly enabling: this consolidate bioisosteric relationship that connects fluorides. Herein, we describe regioselective fluorination unactivated allenes based on I(I)/I(III) catalysis presence inexpensive HF source serves dual role as both nucleophile Brønsted acid activator. This enables variety secondary tertiary prepared: motifs are prevalent across bioactive small molecule spectrum. Facile product derivatisation, concise synthesis multi-vicinal fluorinated products together preliminary validation enantioselective disclosed. expansive potential platform is also demonstrated through organocatalytic oxidation, chlorination arylation allenes. It envisaged transformation will find application molecular design accelerate exploration organofluorine chemical space.

Language: Английский

Citations

1