Data Science Guiding Analysis of Organic Reaction Mechanism and Prediction DOI Open Access
Giovanna S. Tâmega,

Mateus Oliveira Costa,

Ariel de Araujo Pereira

et al.

The Chemical Record, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Abstract Advancements in synthetic organic chemistry are closely related to understanding substrate and catalyst reactivities through detailed mechanistic studies. Traditional investigations labor‐intensive rely on experimental kinetic, thermodynamic, spectroscopic data. Linear free energy relationships (LFERs), exemplified by Hammett relationships, have long facilitated reactivity prediction despite their inherent limitations when using constants or incorporating comprehensive Data‐driven modeling, which integrates cheminformatics with machine learning, offers powerful tools for predicting interpreting mechanisms effectively handling complex multiparameter strategies. This review explores selected examples of data‐driven strategies investigating reaction mechanisms. It highlights the evolution application computational descriptors inference.

Language: Английский

Applying statistical modeling strategies to sparse datasets in synthetic chemistry DOI Creative Commons
Brittany C. Haas, Dipannita Kalyani, Matthew S. Sigman

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

The application of statistical modeling in organic chemistry is emerging as a standard practice for probing structure-activity relationships and predictive tool many optimization objectives. This review aimed tutorial those entering the area chemistry. We provide case studies to highlight considerations approaches that can be used successfully analyze datasets low data regimes, common situation encountered given experimental demands Statistical hinges on (what being modeled), descriptors (how are represented), algorithms modeled). Herein, we focus how various reaction outputs (e.g., yield, rate, selectivity, solubility, stability, turnover number) structures binned, heavily skewed, distributed) influence choice algorithm constructing chemically insightful models.

Language: Английский

Citations

3
Carbene-catalyzed chirality-controlled site-selective acylation of saccharides DOI Creative Commons
Yingguo Liu, Zhixiong Zhong, Yuyang Tang

et al.

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

Published: Jan. 2, 2025

Acylation stands as a fundamental process in both biological pathways and synthetic chemical reactions, with acylated saccharides their derivatives holding diverse applications ranging from bioactive agents to building blocks. A longstanding objective organic synthesis has been the site-selective acylation of without extensive pre-protection alcohol units. In this study, we demonstrate that by simply altering chirality N-heterocyclic carbene (NHC) catalysts, site-selectivity saccharide reactions can be effectively modulated. Our investigation reveals intriguing selectivity shift stems combination factors, including match/mismatch inter- / intramolecular hydrogen bonding between NHC catalyst substrates. These findings provide valuable insights into design reaction engineering, highlighting potential glycoside analysis, such fluorescent labelling, α/β identification, orthogonal selective late-stage modifications. The units synthesis. Here, authors

Language: Английский

Citations

2
Synthesis of chiral sulfilimines by organocatalytic enantioselective sulfur alkylation of sulfenamides DOI Creative Commons
Fucheng Wang, Weiming Xiang, Yiting Xie

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(37)

Published: Sept. 13, 2024

Sulfilimines are versatile synthetic intermediates and important moieties in bioactive molecules. However, their applications drug discovery underexplored, efficient asymmetric methods highly desirable. Here, we report a transition metal–free pentanidium-catalyzed sulfur alkylation of sulfenamides with exclusive chemoselectivity over nitrogen high enantioselectivity. The reaction conditions were mild, wide range enantioenriched aryl alkyl sulfilimines obtained. utility practicability this robust protocol further demonstrated through gram-scale reactions late-stage functionalization drugs.

Language: Английский

Citations

5
Mechanochemical Copper-Catalyzed Synthesis of NH-Sulfonimidamides by Oxidative Amination of Primary Sulfinamides DOI
Peng Wu,

Ling Li,

Yijie Hu

et al.

ACS Sustainable Chemistry & Engineering, Journal Year: 2024, Volume and Issue: 12(43), P. 15875 - 15880

Published: Oct. 15, 2024

A mechanochemical copper-catalyzed oxidative amination of primary sulfinamides has been developed, leading to NH-sulfonimidamides in moderate good yields under solvent-free conditions. Air serves as a terminal oxidant without the need for external additives. The obtained products could be readily converted into both acyclic and cyclic sulfonimidamide derivatives. This approach demonstrates considerable ecological benefits compared solvent-based methods.

Language: Английский

Citations

4
Stereodivergent Synthesis of Complex N-Sulfonimidoyl Lactams via the Castagnoli–Cushman Reaction DOI Creative Commons

Matthew Spock,

James C. Fettinger, Kaori Ando

et al.

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

Published: Jan. 29, 2025

The reactivity between sulfonimidamide-derived imines and cyclic anhydrides has been investigated. Sulfonimidamide readily react with homophthalic anhydride under mild conditions in the presence of non-nucleophilic bases to yield complex lactam products high diastereoselectivity. Furthermore, it was discovered that sulfonimidamide absence a base distinct diastereomer Density functional theory calculations suggest existence an open transition state pathway novel eight-membered base.

Language: Английский

Citations

0
Mechanochemical syntheses of N-acyl sulfinamidines via iron-nitrenoids and their conversions to sulfur(VI) derivatives DOI Creative Commons

Shulei Pan,

Peng Wu, Yijie Hu

et al.

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

Published: April 1, 2025

Language: Английский

Citations

0
Enantioselective Synthesis of Chiral Sulfonimidoyl Fluorides Facilitates Stereospecific SuFEx Click Chemistry DOI

He-sen Huang,

Yi Yuan, Wei Wang

et al.

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
Desymmetrization of Cyclic Sulfonimidamides by Asymmetric Allylation DOI Creative Commons
David A. Gutierrez,

Garrett Toth-Williams,

Croix J. Laconsay

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(34)

Published: May 9, 2024

Herein we report the first transition metal-catalyzed approach to enantioenriched synthesis of cyclic sulfonimidamides relying on commercially available palladium catalysts and ligands. High-throughput experimentation (HTE) was employed identify optimal catalyst system solvent. The method is applied a variety saturated unsaturated rings exhibits highest selectivity for 2-substituted allyl electrophiles. products are further elaborated complex, tricyclic scaffolds. DFT experiments presented herein highlight key ligand substrate interactions leading high levels enantioselectivity.

Language: Английский

Citations

1
Enantioselective Synthesis of Chiral Sulfonimidoyl Fluorides Facilitates Stereospecific SuFEx Click Chemistry DOI Open Access

He-sen Huang,

Yi Yuan, Wei Wang

et al.

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
Desymmetrization of Cyclic Sulfonimidamides by Asymmetric Allylation DOI Creative Commons
David A. Gutierrez,

Garrett Toth-Williams,

Croix J. Laconsay

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(34)

Published: May 9, 2024

Abstract Herein we report the first transition metal‐catalyzed approach to enantioenriched synthesis of cyclic sulfonimidamides relying on commercially available palladium catalysts and ligands. High‐throughput experimentation (HTE) was employed identify optimal catalyst system solvent. The method is applied a variety saturated unsaturated rings exhibits highest selectivity for 2‐substituted allyl electrophiles. products are further elaborated complex, tricyclic scaffolds. DFT experiments presented herein highlight key ligand substrate interactions leading high levels enantioselectivity.

Language: Английский

Citations

0