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

Photocatalytic Functionalization of Dehydroalanine‐Derived Peptides in Batch and Flow DOI Creative Commons
Nikolaos Kaplaneris, Merve Akdeniz, Méritxell Fillols

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(19)

Published: March 18, 2024

Abstract Unnatural amino acids, and their synthesis by the late‐stage functionalization (LSF) of peptides, play a crucial role in areas such as drug design discovery. Historically, LSF biomolecules has predominantly utilized traditional synthetic methodologies that exploit nucleophilic residues, cysteine, lysine or tyrosine. Herein, we present photocatalytic hydroarylation process targeting electrophilic residue dehydroalanine (Dha). This possesses an α , β ‐unsaturated moiety can be combined with various arylthianthrenium salts, both batch flow reactors. Notably, setup proved instrumental for efficient scale‐up, paving way unnatural acids peptides substantial quantities. Our approach, being inherently mild, permits diversification even when they contain sensitive functional groups. The readily available salts facilitate seamless integration Dha‐containing wide range arenes, blueprints, natural products, culminating creation unconventional phenylalanine derivatives. synergistic effect high group tolerance modular characteristic aryl electrophile enables peptide conjugation ligation conditions.

Language: Английский

Citations

15
Alkene Thianthrenation Unlocks Diverse Cation Synthons: Recent Progress and New Opportunities DOI Creative Commons
Min Ji Kim, Karina Targos, Dylan E. Holst

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(16)

Published: Feb. 8, 2024

Oxidative alkene functionalization reactions are a fundamental class of complexity-building organic transformations. However, the majority established approaches rely on electrophilic reagents that limit diversity groups can be installed. Recent advances have new approach instead relies transformation alkenes into thianthrene-derived cationic electrophiles. These linchpin intermediates generated selectively and undergo diverse array mechanistically distinct with abundant nucleophiles. Taken together, this unlocks suite net oxidative transformations been elusive using conventional strategies. This Minireview describes these is organized around three synthons formally accessible from via thianthrenation: 1) alkenyl cations; 2) vicinal dications; 3) allyl cations. Throughout Minireview, we illustrate how thianthrenium salts address key limitations endemic to classic alkene-derived electrophiles highlight mechanistic origins distinctions wherever possible.

Language: Английский

Citations

9
Oxetane Synthesis via Alcohol C–H Functionalization DOI Creative Commons

Subhasis Paul,

Dario Filippini, Filippo Ficarra

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(29), P. 15688 - 15694

Published: July 18, 2023

Oxetanes are strained heterocycles with unique properties that have triggered significant advances in medicinal chemistry. However, their synthesis still presents challenges limit the use of this class compounds practical applications. In Letter, we present a methodology introduces new synthetic disconnection to access oxetanes from native alcohol substrates. The generality approach is demonstrated by application late-stage functionalization chemistry, which further exploited develop single-step known bioactive steroid derivative previously required at least four steps available precursors.

Language: Английский

Citations

22
Modular and Practical 1,2‐Aryl(Alkenyl) Heteroatom Functionalization of Alkenes through Iron/Photoredox Dual Catalysis** DOI Creative Commons
Weigang Zhang, Tao Liu, Hwee Ting Ang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(44)

Published: Sept. 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.

Language: Английский

Citations

17
Mechanism of Z-Selective Allylic Functionalization via Thianthrenium Salts DOI
Karina Targos, Achyut Ranjan Gogoi, Ángel Rentería‐Gómez

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(20), P. 13689 - 13696

Published: May 13, 2024

A detailed mechanistic study of the Z-selective allylic functionalization via thianthrenium salts is presented. Kinetic analyses, deuterium labeling experiments, and computational methods are used to rationalize observed reactivity selectivity. We find that reaction proceeds a rate-determining stereodetermining deprotonation an alkenylthianthrenium species. The Z-configuration resultant ylide translated into Z-allylic amine product through sequence subsequent fast irreversible steps: protonation form electrophile then regioselective substitution by nucleophile. In step, studies identified series stabilizing nonbonding interactions in Z-alkene-forming transition state contribute stereoselectivity.

Language: Английский

Citations

6
Highly Regioselective Dichalcogenation of Alkenyl Sulfonium Salts to Access 1,1-Dichalcogenalkenes DOI
Jie Zhu, Yun Ye,

Yifei Yan

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(28), P. 5324 - 5328

Published: July 7, 2023

An unprecedented geminal olefinic dichalcogenation of alkenyl sulfonium salts with dichalcogenides ArYYAr (Y = S, Se, Te) is reported, providing various trisubstituted 1,1-dichalcogenalkenes [Ar1CH C(YAr2)2] in a highly selective manner under mild and catalyst-free conditions. The key process involves the formation two C-Y bonds via sequential cross-coupling C-H chalcogenation. A mechanistic rationale further supported by control experiments density functional theory calculations.

Language: Английский

Citations

15
Ring-Opening Sulfonylation of Cyclic Sulfonium Salts with Sodium Sulfinates under Transition-Metal- and Additive-Free Conditions DOI
Lihua Yang,

Xiangda Liu Xiangda Liu,

Chu Liu

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(17), P. 12668 - 12680

Published: Aug. 9, 2024

Incorporating a sulfonyl group into parent molecules has been shown to effectively improve their synthetic applications and bioactivities. In this study, we present straightforward practical approach for the ring-opening reaction of alkenyl–aryl sulfonium salts with sodium sulfinates produce range sulfur-containing alkyl sulfones. This method offers benefits mild conditions, easily accessible raw materials, wide substrate applicability, good functional compatibility, operational simplicity. Importantly, resulting products can be readily converted sulfoxides, sulfones, sulfoximines, some heterocyclic compounds.

Language: Английский

Citations

5
Arylthianthrenium Salts for Triplet Energy Transfer Catalysis DOI Creative Commons
Yuan Cai,

Triptesh Kumar Roy,

Till J. B. Zähringer

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(44), P. 30474 - 30482

Published: Oct. 28, 2024

Sigma bond cleavage through electronically excited states allows synthetically useful transformations with two radical species. Direct excitation of simple aryl halides to form both and halogen radicals necessitates UV-C light, so undesired side reactions are often observed specific equipment is required. Moreover, only extended π systems comparatively low triplet energy applicable transfer catalysis. Here we show the conceptual advantages arylthianthrenium salts (ArTTs) for catalysis high efficiency compared conventional (pseudo)halides their utility in arylation ethylene. The fundamental advance enabled by ArTTs that may originate large part from electronic interplay between distinct sulfur atoms tricyclic thianthrene scaffold, which not accessible either or other sulfonium salts.

Language: Английский

Citations

5
Photoinduced Regioselective Fluorination and Vinylation of Remote C(sp3)–H Bonds Using Thianthrenium Salts DOI

Mengqi Luo,

Shibo Zhu,

Chao Yang

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(20), P. 4388 - 4393

Published: May 16, 2024

Herein, a photoredox-driven practical protocol for fluorinated alkene synthesis using easily accessible and modular thianthrenium salts with electron-withdrawing alkynes or propargyl alcohols is reported. Vinyl radical intermediates, formed by the reaction between alkyl trifluoromethyl electronically diverse alkynes, can mediate key 1,5-HAT process of regioselective C(sp3)–H fluorination vinylation. This provides straightforward access to structurally trifluoromethyl- distally fluoro-functionalized products in 21–79% yields broad substrate range under mild photocatalytic conditions.

Language: Английский

Citations

4
Synthesis of S-alkyl phosphorothioates/phosphorodithioates via ring-opening reaction of sulfonium salts with S8, H-phosphonates or P4S10, and alcohols DOI
Lihua Yang, Lin Chen,

Bei Li

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(20), P. 5731 - 5740

Published: Jan. 1, 2024

A simple and practical method for the synthesis of S -alkyl phosphorothioates/phosphorodithioates through three-component reaction cyclic sulfonium salts with 8 , H -phosphonates, or P 4 10 alcohols was readily developed.

Language: Английский

Citations

4