A Photochemical Strategy for the Conversion of Nitroarenes into Rigidified Pyrrolidine Analogues DOI
Esteban Matador, Michael J. Tilby, Iakovos Saridakis

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(50), P. 27810 - 27820

Published: Dec. 7, 2023

Bicyclic amines are important motifs for the preparation of bioactive materials. These species have well-defined exit vectors that enable accurate disposition substituents toward specific areas chemical space. Of all possible skeletons, 2-azabicyclo[3.2.0]heptane framework is virtually absent from MedChem libraries due to a paucity synthetic methods its preparation. Here, we report modular strategy utilizes nitroarenes as flat and easy-to-functionalize feedstocks assembly these sp3-rich Mechanistically, this approach exploits two concomitant photochemical processes sequentially ring-expand nitroarene into an azepine then fold it rigid bicycle pyrroline by means singlet nitrene-mediated nitrogen insertion excited-state-4π electrocyclization. A following hydrogenolysis provides, with full diastereocontrol, desired bicyclic amine derivatives whereby aromatic substitution pattern has been translated one three-dimensional heterocycle. molecules can be considered pyrrolidine analogues orientation their substituents. Furthermore, unsupervised clustering expansive virtual database saturated N-heterocycles revealed effective isosteres rigidified piperidines. Overall, platform enables conversion complex heterocycles potential interest drug development.

Language: Английский

A deconstruction-reconstruction strategy for pyrimidine diversification DOI

Benjamin J. H. Uhlenbruck,

Celena M. Josephitis,

Louis de Lescure

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8019), P. 87 - 93

Published: May 2, 2024

Language: Английский

Citations

19
Photocatalytic furan-to-pyrrole conversion DOI

D.B. Kim,

Jaehyun You,

D. H. Lee

et al.

Science, Journal Year: 2024, Volume and Issue: 386(6717), P. 99 - 105

Published: Oct. 3, 2024

The identity of a heteroatom within an aromatic ring influences the chemical properties that heterocyclic compound. Systematically evaluating effect single atom, however, poses synthetic challenges, primarily as result thermodynamic mismatches in atomic exchange processes. We present photocatalytic strategy swaps oxygen atom furan with nitrogen group, directly converting into pyrrole analog intermolecular reaction. High compatibility was observed various derivatives and nucleophiles commonly used drug discovery, late-stage functionalization furnished otherwise difficult-to-access pyrroles from naturally occurring furans high molecular complexity. Mechanistic analysis suggested polarity inversion through electron transfer initiates redox-neutral processes at room temperature.

Language: Английский

Citations

18
Interrogation of Enantioselectivity in the Photomediated Ring Contractions of Saturated Heterocycles DOI
Sojung F. Kim, Jordan P. Liles, Michaelyn C. Lux

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

We recently reported a chiral phosphoric acid (CPA) catalyzed enantioselective photomediated ring contraction of piperidines and other saturated heterocycles. By extruding single heteroatom from ring, this transformation builds desirable C(sp3)–C(sp3) bonds in the contracted products; however, origins enantioselectivity remain poorly understood. In work, has been explored across an expanded structurally diverse substrate scope, revealing wide range enantioselectivities (0–99%) using two distinct CPA catalysts. Mechanistic investigations support rate-determining excitation that generates short-lived achiral intermediates are intercepted by enantiodetermining closure. The effects competitive uncatalyzed reactivity light-driven reversibility closure on have elucidated. Statistical models were built regressing scope against key structural features products for both resultant suggested factors influence response each catalyst enabled rational modification pharmaceutically relevant target molecule to improve enantioselectivity. Finally, density functional theory (DFT)-based transition state analysis identified noncovalent interactions with correlated unique selectivity-relevant uncovered through statistical modeling. Our findings not only offer comprehensive insight into system but should also aid future development related CPA-catalyzed reactions.

Language: Английский

Citations

4
Tandem C/N-Difunctionalization of Nitroarenes: Reductive Amination and Annulation by a Ring Expansion/Contraction Sequence DOI
Gen Li, Marissa N. Lavagnino, Siraj Z. Ali

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 145(1), P. 41 - 46

Published: Dec. 23, 2022

A synthetic method for the reductive transformation of nitroarenes into ortho-aminated and -annulated products is reported. The operates via exhaustive deoxygenation by an organophosphorus catalyst a mild terminal reductant to access aryl nitrenes, which after ring expansion, are trapped amine nucleophiles give dearomatized 2-amino-3H-azepines. Treatment these ring-expanded intermediates with acyl electrophiles triggers 6π electrocyclization extrude nitrogen atom restore aromaticity phenyl ring, delivers C–H functionalization 2-aminoanilide benzimidazole products.

Language: Английский

Citations

47
Single-atom skeletal editing of 2H-indazoles enabled by difluorocarbene DOI
Yao Zhou,

F Chen,

Ziru Li

et al.

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(7), P. 1975 - 1981

Published: May 11, 2023

Language: Английский

Citations

29
Nitrogen atom insertion into arenols to access benzazepines DOI Creative Commons
Yi He, Juanjuan Wang,

Tongtong Zhu

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(7), P. 2612 - 2617

Published: Jan. 1, 2024

Advances in site-selective molecular editing have enabled structural modification on complex molecules.

Language: Английский

Citations

16
Synthesis of benzenes from pyridines via N to C switch DOI Creative Commons

Aífe Conboy,

Michael F. Greaney

Chem, Journal Year: 2024, Volume and Issue: 10(6), P. 1940 - 1949

Published: June 1, 2024

The skeletal editing of heteroarenes introduces new disconnections to the chemistry lexicon, enabling interconversion ring systems via selective breaking/re-making carbon framework. We describe one-pot transformation pyridines into benzene derivatives, using a nucleophilic addition ring-opening/ring-closing (ANRORC) process with soft nucleophiles such as malonate. Triflic anhydride activates pyridine ANRORC synthesis an isolable amine intermediate, which aromatizes on simple heating. reaction has been exemplified room temperature protocol, along direct syntheses drug-like, tertiary-alkylated, and isotopically labeled benzoates.

Language: Английский

Citations

14
Visible photons as ideal reagents for the activation of coloured organic compounds DOI Creative Commons
Lorenzo Di Terlizzi, Luca Nicchio,

Stefano Protti

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(10), P. 4926 - 4975

Published: Jan. 1, 2024

In search for the perfect wave(length). This review is dedicated to recent efforts in development of visible light driven photochemical strategies occurring coloured organic compounds.

Language: Английский

Citations

13
Synthesis of Collidine from Dinitrogen via a Tungsten Nitride DOI

Lukas Eberle,

Joachim Ballmann

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(12), P. 7979 - 7984

Published: March 15, 2024

The synthesis of pyridines from dinitrogen in homogeneous solution is known to be challenging considering that an N2 cleavage step needs combined with two N–C coupling steps. Herein, a tungsten complex bearing tailor-made 2,2′-(tBu2As)2-substituted tolane ligand scaffold was shown split afford the corresponding nitride, which not case for (iPr2As)2-substituted derivative. former nitride then reacted 2,4,6-trimethylpyrylium triflate, led formation oxo complex, along collidine. Over course this reaction, O atom pyrylium starting material replaced N via hitherto unprecedented skeletal editing process.

Language: Английский

Citations

12
N-Oxide-to-Carbon Transmutations of Azaarene N-Oxides DOI
Nicholas Falcone, Sam He, John Hoskin

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(20), P. 4280 - 4285

Published: May 13, 2024

Reactions that change the identity of an atom within a ring system are emerging as valuable tools for site-selective editing molecular structures. Herein, we describe expansion underdeveloped transformation directly converts azaarene-derived N-oxides to all-carbon arenes. This transmutation exhibits good functional group tolerance and replaces N-oxide moiety with either unsubstituted, substituted, or isotopically labeled carbon atoms in single laboratory operation.

Language: Английский

Citations

11