Photocatalytic Late-Stage C–H Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(8), P. 4237 - 4352

Published: Jan. 24, 2023

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C–H functionalization approaches that make use low energy photons as a controllable source. Compared to traditional strategies, photocatalysis paves the way toward complementary and/or previously unattainable regio- chemoselectivities. Merging compelling benefits with workflow offers potentially unmatched arsenal tackle drug development campaigns beyond. This Review highlights photocatalytic strategies small-molecule drugs, agrochemicals, natural products, classified according targeted bond newly formed one. Emphasis is devoted identifying, describing, comparing main mechanistic scenarios. draws critical comparison between established ionic chemistry photocatalyzed radical-based manifolds. aims establish current state-of-the-art illustrate key unsolved challenges be addressed in future. authors aim introduce general readership functionalization, specialist practitioners evaluation methodologies, potential for improvement, future uncharted directions.

Language: Английский

---

A Perspective on Late-Stage Aromatic C–H Bond Functionalization

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(6), P. 2399 - 2414

Published: Jan. 27, 2022

Late-stage functionalization of C-H bonds (C-H LSF) can provide a straightforward approach to the efficient synthesis functionalized complex molecules. However, LSF is challenging because bond must be in presence various other functional groups. In this Perspective, we evaluate aromatic on basis four criteria─reactivity, chemoselectivity, site-selectivity, and substrate scope─and our own views current challenges as well promising strategies areas growth going forward.

Language: Английский

---

A general arene C–H functionalization strategy via electron donor–acceptor complex photoactivation

Nature Chemistry, Journal Year: 2022, Volume and Issue: 15(1), P. 43 - 52

Published: Dec. 5, 2022

Language: Английский

---

Sustainable Thioetherification via Electron Donor–Acceptor Photoactivation Using Thianthrenium Salts

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(22)

Published: March 16, 2022

Abstract The synthesis of sulfides has been widely studied because this functional subunit is prevalent in biomolecules and pharmaceuticals, as well being a useful synthetic platform for further elaboration. Thus, various methods to build C−S bonds have developed, but typically they require the use precious metals or harsh conditions. Electron donor–acceptor (EDA) complex photoactivation strategies emerged versatile sustainable ways achieve bond formation, avoiding challenges associated with previous methods. This work describes an open‐to‐air, photoinduced, site‐selective C−H thioetherification from readily available reagents via EDA formation that tolerates wide range different groups. Moreover, C(sp 2 )−halogen remain intact using protocol, allowing late‐stage installation sulfide motif bioactive scaffolds, while yet modification through more traditional C−X cleavage protocols. Additionally, mechanistic investigations support envisioned scenario.

Language: Английский

---

Organothianthrenium salts: synthesis and utilization

Chemical Science, Journal Year: 2022, Volume and Issue: 13(46), P. 13690 - 13707

Published: Jan. 1, 2022

This review summarizes the synthesis of diverse organothianthrenium salts from various precursors and their applications in organic to forge new C–C, C–H C–heteroatom bonds by C–S bond cleavage with different mechanistic considerations.

Language: Английский

---

Photoinduced Copper-Catalyzed Late-Stage Azidoarylation of Alkenes via Arylthianthrenium Salts

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(25), P. 13542 - 13548

Published: June 12, 2023

The arylethylamine pharmacophore is conserved across a range of biologically active natural products and pharmaceuticals, particularly in molecules that act on the central nervous system. Herein, we present photoinduced copper-catalyzed azidoarylation alkenes at late stage with arylthianthrenium salts, allowing access to highly functionalized acyclic (hetero)arylethylamine scaffolds are otherwise difficult access. A mechanistic study consistent rac-BINAP-CuI-azide (2) as photoactive catalytic species. We show utility new method by expedient synthesis racemic melphalan four steps through C-H functionalization.

Language: Английский

---

Cu-Mediated Thianthrenation and Phenoxathiination of Arylborons

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(18), P. 10431 - 10440

Published: April 26, 2023

Great success in synthetic chemistry is motivated by the development of novel and reactive linchpins for carbon-carbon carbon-heteroatom bond formation reactions, which has dramatically altered chemists' approach to building molecules. Herein, we report ready synthesis aryl sulfonium salts, a versatile electrophilic linchpin, via Cu-mediated thianthrenation phenoxathiination commercially available arylborons with thianthrene phenoxathiine, providing series salts high efficiency. More importantly, leveraging sequential Ir-catalyzed C-H borylation arylborons, formal arenes also achieved. The undirected normally occurred at less steric hindrance position, thus complementary method comparison thianthrenation. This process capable late-stage functionalization pharmaceuticals, might find wide applications both industry academic sectors.

Language: Английский

---

A Practical and Regioselective Strategy for Aromatic C–H Difunctionalization via Site-Selective C–H Thianthrenation

Organic Letters, Journal Year: 2024, Volume and Issue: 26(9), P. 1813 - 1818

Published: Feb. 22, 2024

Herein, we present a novel Catellani-type reaction that employed aryl-thianthrenium salts as aryl substrates to trigger the subsequent palladium/norbornene cooperatively catalyzed progress. This strategy can achieve site-selective C–H difunctionalization of compounds without directing groups or known initiating reagent. A series functionalized syntheses bioactive molecules further demonstrated potential this strategy.

Language: Английский

---

Standardized Approach for Diversification of Complex Small Molecules via Aryl Thianthrenium Salts

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

Published: Jan. 21, 2025

Thianthrenation is a useful strategy for the late-stage diversification of complex small molecules owing to positional selectivity and synthetic versatility thianthrenium salts as electrophilic linchpins. However, substrate-dependent identification suitable reaction conditions thianthrenation can be difficult. Reported functionalization vary significantly and, in some instances, lack robustness practicality. Herein, we report generalized approach preparation two manifolds practical, robust, parallel salts.

Language: Английский

---

Metal-free allylic C–H nitrogenation, oxygenation, and carbonation of alkenes by thianthrenation

Chemical Science, Journal Year: 2021, Volume and Issue: 13(4), P. 1003 - 1008

Published: Dec. 20, 2021

Selective functionalization of allylic C-H bonds into other chemical is among the most straightforward and attractive, yet challenging transformations. Herein, a transition-metal-free protocol for direct nitrogenation, oxygenation, carbonation alkenes by thianthrenation was developed. This operationally simple allows unified amination, esterification, etherification, arylation vinyl thianthrenium salts. Notably, reaction furnishes multialkyl substituted amines, ammonium salts, sulfonyl amides, esters, ethers in good yields. The proceeds under mild conditions with excellent functional group tolerance could be applied to late-stage allylation natural products, drug molecules peptides chemoselectivity.

Language: Английский

---