Organic Letters, Journal Year: 2024, Volume and Issue: 26(45), P. 9676 - 9681
Published: Nov. 6, 2024
A facile palladium-catalyzed synthesis of thiaphenanthridinones from sulfinate esters and 2-borylanilines is disclosed. Various sulfur analogs phenanthridinones were synthesized by bromide-selective cross-coupling cyclization in one step. Further transformations the obtained allowed preparing a broad range thiaphenanthridinone derivatives involving bioactive compounds.
Language: Английский
Chemical Communications, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Recent sulfinate esters chemistry is summarized in this feature article. Efficient methods to synthesize diverse from readily available starting materials and various modern transformations of are introduced.
Language: Английский
Citations
0
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: March 15, 2025
The study of the stereochemistry organic sulfur compounds has been ongoing for over a century, with S-chirogenic pharmacophores playing an essential role in drug discovery within bioscience and medicinal chemistry. Traditionally, synthesis sulfinamides featuring stereogenic sulfur(IV) centers involves complex, multistep process that often depends on chiral auxiliaries or kinetic resolution. Here, we introduce effective versatile method synthesizing diverse classes through selective aryl alkenyl addition to sulfinylamines. This is catalysed by nickel cobalt complex under reductive conditions, eliminating need preformed organometallic reagents. facilitates incorporation array halides at position, enabling their integration into various biologically significant pharmacophores. Our detailed mechanistic investigations density functional theory calculations provide insights reaction pathway, particularly highlighting enantiocontrol mode during process. play authors report methodology asymmetric sulfinylamines via common-Earth-metal catalysis.
Language: Английский
Citations
0
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: March 28, 2025
Heteroatom-doped polyaromatic hydrocarbons show great potential for advancing photoelectric materials. SVI=N doping, characterized by soft-hard atom binding, donor-acceptor transmission, and chiroptical tuning, provides a powerful approach further optimizing the performance functionality of these However, introduction chiral sulfur(VI) has been formidable challenge due to intricate enantioselective discrimination embedded linkages with heteroatoms in systems. Herein, we establish an Pd-catalyzed desymmetrization diaryl sulfoximines sulfondiimines access SVI=N-doped heterocycles high yields enantioselectivities. The flexibility rigidity molecule distinct effect on enantioselectivity. split aromatic compounds exhibit C-H···π interactions involving additive TMCPA ligand S-aryl motif, producing (R)-configuration, while combined opposite (S)-configuration restricted bond rotation. photophysical study demonstrates carbazole-based heterocycle intense double absorption peaks favorable luminescence dissymmetry factor.
Language: Английский
Citations
0
Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown
Published: April 28, 2025
Sulfoximines are increasingly utilized in pharmaceuticals and agrochemicals with all sulfoximine clinical candidates incorporating either an S-methyl or S-cyclopropyl substituent. Here, we report on a general efficient sequence for the asymmetric synthesis of both these substitution patterns. The sulfilimine intermediates by first Ru-catalyzed enantioselective alkylation sulfenamides enables examples S-alkylation monosubstituted diazo compounds. reaction proceeds at ≤1 mol % Ru-catalyst loading, tert-butyl diazoacetate, high yields ≥98:2 er achieved exceedingly broad range sulfenamides, including S-(hetero)aryl, -alkenyl, -methyl, -benzyl, -branched alkyl, -tert-butyl substituents sterically electronically diverse N-acyl groups. Sulfenamides derived from densely functionalized advanced drug also alkylated 99:1 er. After oxidation N-pivaloyl S-tert-butyl acetate substituted to corresponding sulfoximine, treatment trifluoracetic acid aprotic solvent resulted decarboxylation while aqueous HCl cleavage group give NH sulfoximine. Alternatively, dibromoethane followed acid-mediated provided preclinical candidate LTGO-33 formal phase II ART0380 demonstrate utility disclosed approach.
Language: Английский
Citations
0
Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(36), P. 25350 - 25360
Published: Sept. 2, 2024
Stereoselective synthesis utilizing small-molecule catalysts, particularly N-heterocyclic carbene (NHC), has facilitated swift access to enantioenriched molecules through diverse activation modes and NHC-bound reactive intermediates. While carbonyl derivatives, imines, "activated" alkenes have been extensively investigated, the exploration of heteroatom-centered analogues intermediates long neglected, despite significant potential for novel chemical transformations they offer once recognized. Herein, we disclose a carbene-catalyzed new mode by generating unique sulfinyl azolium from nucleophilic addition in situ-generated mixed sulfinic anhydride Combined experimental computational mechanistic investigations pinpoint chiral NHC-catalyzed formation intermediate as enantio-determining step. The "S"-based imparts high efficiency catalytic construction sulfur-stereogenic compounds, giving rise sulfinate esters with yields enantioselectivities under mild conditions. Notably, distinct most enantioselective focusing on "C" central products, our study realizes carbene-catalyst control over "S" stereocenters via direct asymmetric S-O bond first time. Furthermore, these sulfinyl-containing products could serve versatile synthetic platforms
Language: Английский
Citations
3
Chem, Journal Year: 2024, Volume and Issue: 10(5), P. 1332 - 1334
Published: April 24, 2024
Language: Английский
Citations
2
Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 5, 2024
Abstract Sulfur‐centered electrophilic ‘warheads’ have emerged as key components for chemical proteomic probes through sulfur‐exchange chemistry (SuFEx) with protein nucleophiles. Among these functional groups, sulfonimidoyl fluorides (SIFs) stand out their modifiable sites, tunable electrophilicities, and chiral sulfur‐center, presenting exciting possibilities new covalent probes. However, the synthetic access to SIFs has been a challenge, limiting exploration applications. In this study, we describe convenient route obtain from readily available sulfenamides via series of one‐pot tandem reactions high enantiomeric excess (ees). The resulting were further converted into diverse array S(VI) derivatives under mild conditions or in buffer solutions. Most significantly, specificity ligation experiments underscored critical role sulfur‐center chirality design screening more‐selective therapeutics.
Language: Английский
Citations
2
Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(42)
Published: July 26, 2024
Abstract A general phase‐transfer catalyst (PTC) mediated enantioselective alkylation of N ‐acylsulfenamides is reported. Essential to achieving high selectivity was the use triethylacetyl sulfenamide protecting group along with aqueous KOH as base under biphasic conditions enable reaction be performed at −40 °C. With these key parameters, enantiomeric ratios up 97.5 : 2.5 newly generated chiral sulfur center were achieved an inexpensive cinchona alkaloid derived PTC. Broad scope and excellent functional compatibility observed for a variety S ‐(hetero)aryl branched unbranched ‐alkyl sulfenamides. Moreover, achieve opposite enantiomer, pseudoenantiomeric designed synthesized from cinchonidine. Given that sulfoximines are bioactive pharmacophore ever‐increasing interest, selected product sulfilimines oxidized corresponding subsequent reductive cleavage affording free‐NH in yields. The utility disclosed method further demonstrated by efficient asymmetric synthesis atuveciclib, phase I clinical candidate which only HPLC separation had previously been reported isolation desired ( R )‐sulfoximine stereoisomer.
Language: Английский
Citations
1
Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 5, 2024
Abstract Sulfur‐centered electrophilic ‘warheads’ have emerged as key components for chemical proteomic probes through sulfur‐exchange chemistry (SuFEx) with protein nucleophiles. Among these functional groups, sulfonimidoyl fluorides (SIFs) stand out their modifiable sites, tunable electrophilicities, and chiral sulfur‐center, presenting exciting possibilities new covalent probes. However, the synthetic access to SIFs has been a challenge, limiting exploration applications. In this study, we describe convenient route obtain from readily available sulfenamides via series of one‐pot tandem reactions high enantiomeric excess (ees). The resulting were further converted into diverse array S(VI) derivatives under mild conditions or in buffer solutions. Most significantly, specificity ligation experiments underscored critical role sulfur‐center chirality design screening more‐selective therapeutics.
Language: Английский
Citations
1
Organic Letters, Journal Year: 2024, Volume and Issue: 26(45), P. 9676 - 9681
Published: Nov. 6, 2024
A facile palladium-catalyzed synthesis of thiaphenanthridinones from sulfinate esters and 2-borylanilines is disclosed. Various sulfur analogs phenanthridinones were synthesized by bromide-selective cross-coupling cyclization in one step. Further transformations the obtained allowed preparing a broad range thiaphenanthridinone derivatives involving bioactive compounds.
Language: Английский
Citations
1