Catalyst and Medium Control over Rebound Pathways in Manganese-Catalyzed Methylenic C–H Bond Oxidation DOI Creative Commons
Marco Galeotti, Massimo Bietti, Miguel Costas

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 8904 - 8914

Published: March 20, 2024

The C(sp3)–H bond oxygenation of a variety cyclopropane containing hydrocarbons with hydrogen peroxide catalyzed by manganese complexes aminopyridine tetradentate ligands was carried out. Oxidations were performed in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and 2,2,2-trifluoroethanol (TFE) using different catalysts carboxylic acid co-ligands, where steric electronic properties systematically modified. Functionalization selectively occurs at the most activated C–H bonds that are α- to cyclopropane, providing access carboxylate or 2,2,2-trifluoroethanolate transfer products, no competition, favorable cases, from generally dominant hydroxylation reaction. formation mixtures unrearranged rearranged esters (oxidation HFIP presence acid) ethers TFE) full control over diastereoselectivity observed, confirming involvement delocalized cationic intermediates these transformations. Despite such complex mechanistic scenario, fine-tuning catalyst sterics electronics leveraging on relative contribution pathways reaction mechanism, product chemoselectivity could be achieved. Taken together, results reported herein provide powerful catalytic tools rationally manipulate ligand oxidations hydrocarbons, delivering novel products good yields and, some outstanding selectivities, expanding available toolbox for development synthetically useful functionalization procedures.

Language: Английский

Adoption of Electrochemistry within the Pharmaceutical Industry: Insights from an Industry-Wide Survey DOI
Antonio C. Ferretti, Benjamin Cohen, Lin Deng

et al.

Organic Process Research & Development, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Language: Английский

Citations

2
Controlling One- or Two-Electron Oxidation for Selective Amine Functionalization by Alternating Current Frequency DOI
Disni Gunasekera, Jyoti P. Mahajan,

Yanick Wanzi

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(22), P. 9874 - 9882

Published: May 27, 2022

Here, we report a unique electrosynthetic method that enables the selective one-electron oxidation of tertiary amines to generate α-amino radical intermediates over two-electron iminium cations, providing easy access arylation products by simply applying an optimal alternating current (AC) frequency. More importantly, have discovered electrochemical descriptor from cyclic voltammetry studies predict AC frequency for various amine substrates, circumventing time-consuming trial-and-error methods optimizing reaction conditions. This new development in electrolysis provides alternative strategy solving challenging chemoselectivity problems synthetic organic chemistry.

Language: Английский

Citations

45
Mechanistic Aspects of the Electrochemical Oxidation of Aliphatic Amines and Aniline Derivatives DOI Creative Commons
Ashwin K. V. Mruthunjaya, Angel A. J. Torriero

Molecules, Journal Year: 2023, Volume and Issue: 28(2), P. 471 - 471

Published: Jan. 4, 2023

The electrochemical oxidation of amines is an essential alternative to the conventional chemical transformation that provides critical routes for synthesising and modifying a wide range chemically useful molecules, including pharmaceuticals agrochemicals. As result, anodic reactivity these compounds has been extensively researched over past seven decades. However, different mechanistic aspects have never discussed from comprehensive general point view. This review examines mechanism aliphatic amines, amides, aniline derivatives, carbamates, lactams, either directly oxidised at electrode surfaces or indirectly by reversible redox molecule, in which reactive form was generated situ. mechanisms are compared simplified understand all possible pathways using only few mechanisms. Examples application reactions also provided.

Language: Английский

Citations

37
Emerging reaction technologies in pharmaceutical development: Challenges and opportunities in electrochemistry, photochemistry, and biocatalysis DOI
Benjamin Cohen, Dan Lehnherr, Melda Sezen-Edmonds

et al.

Process Safety and Environmental Protection, Journal Year: 2023, Volume and Issue: 192, P. 622 - 637

Published: March 3, 2023

Language: Английский

Citations

27
Late-stage modification of bioactive compounds: Improving druggability through efficient molecular editing DOI Creative Commons

Tongyu Huo,

Xin-Yi Zhao, Zengrui Cheng

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(3), P. 1030 - 1076

Published: Nov. 18, 2023

Synthetic chemistry plays an indispensable role in drug discovery, contributing to hit compounds identification, lead optimization, candidate drugs preparation, and so on. As Nobel Prize laureate James Black emphasized, "the most fruitful basis for the discovery of a new is start with old drug"

Language: Английский

Citations

23
Electrochemical Vicinal C–H Difunctionalization of Saturated Azaheterocycles DOI
Gourab Kundu, Tristan H. Lambert

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(3), P. 1794 - 1798

Published: Jan. 8, 2024

A method to functionalize two vicinal C–H bonds of saturated azaheterocycles is described. The procedure involves subjecting the substrate a mixture hydrochloric acid, acetic and anhydride in an undivided electrochemical cell at constant current, resulting stereoselective conversion corresponding α-acetoxy-β-chloro derivative. α-position can be readily substituted with range other groups, including alkyl, aryl, allyl, alkynyl, alkoxy, or azido functionalities. Furthermore, we demonstrate that β-chloro position engaged Suzuki cross-coupling. This protocol thus enables rapid diversification simple five-, six-, seven-membered adjacent positions.

Language: Английский

Citations

9
A Scalable Solution to Constant-Potential Flow Electrochemistry DOI
Jeremy Griffin, Kaid C. Harper, Simon Velasquez Morales

et al.

Organic Process Research & Development, Journal Year: 2024, Volume and Issue: 28(5), P. 1877 - 1885

Published: March 1, 2024

The burgeoning interest in new electrochemical methods holds promise to provide a plethora of strategic disconnections for pharmaceutical compounds that are safer, less wasteful, and more streamlined than traditional chemical strategies. use organic electrochemistry the commercial production pharmaceuticals is exceedingly rare due lack modular infrastructure. Herein we describe cascading continuous stirred tank reactors with individual cell potential control applied over reaction "stages" which demonstrate balance between high selectivity throughput necessary be viable strategy space. Using degree afforded by this reactor design, 1 kg demonstration was achieved 9 h yield (2.6 kg/day throughput).

Language: Английский

Citations

8
Metal-free electrochemical dihydroxylation of unactivated alkenes DOI Creative Commons
Min Liu, Tian Feng, Yanwei Wang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 13, 2023

Herein, a metal-free electrochemical dihydroxylation of unactivated alkenes is described. The transformation proceeds smoothly under mild conditions with broad range alkenes, providing valuable and versatile dihydroxylated products in moderate to good yields without the addition costly transition metals stoichiometric amounts chemical oxidants. Moreover, this method can be applied natural pharmaceutical derivatives, further demonstrating its synthetic utility. Mechanistic studies have revealed that iodohydrin epoxide intermediate are formed during reaction process.

Language: Английский

Citations

20
Polymer up-cycling by mangana-electrocatalytic C(sp3)–H azidation without directing groups DOI Creative Commons
Isaac Maksso, Ramesh C. Samanta, Yifei Zhan

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(30), P. 8109 - 8118

Published: Jan. 1, 2023

The chemical up-cycling of polymers into value-added materials offers a unique opportunity to place plastic waste in new value chain towards circular economy. Herein, we report the selective polystyrenes and polyolefins C(sp3)-H azidated under electrocatalytic conditions. functionalized were obtained with high retention mass average molecular functionalization through chemo-selective mangana-electrocatalysis. Our strategy proved be broadly applicable variety homo- copolymers. Polyethylene, polypropylene as well post-consumer polystyrene by this approach, thereby avoiding use hypervalent-iodine reagents stoichiometric quantities means electrocatalysis. This study, hence, represents oxidant-free polymer electro-oxidation. electrocatalysis scalable, which highlights its feature for green hydrogen economy evolution reaction (HER).

Language: Английский

Citations

19
C(sp3)–H Aerobic Alkenylation of Tetrahydroisoquinolines via Organic Electrosynthesis DOI

Zeng He,

Huilin Liu,

Zhenhua Wang

et al.

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(9), P. 6203 - 6208

Published: April 14, 2023

A method for the C(sp3)-H alkenylation of N-aryl-tetrahydroisoquinoline (THIQ) has been developed by combination electrooxidation and a copper catalyst. The corresponding products were obtained with good to excellent yields under mild conditions. Besides, addition TEMPO as an electron mediator is crucial this transformation, since oxidative reaction could proceed low electrode potential. In addition, catalytic asymmetric variant also demonstrated enantioselectivity.

Language: Английский

Citations

17