Skeletal Transformation of Unactivated Arenes Enabled by a Low-Temperature Dearomative (3 + 2) Cycloaddition DOI
Sajan Pradhan, Fahimeh Mohammadi, Jean Bouffard

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(22), С. 12214 - 12223

Опубликована: Май 24, 2023

Simple aromatic compounds like benzene are abundant feedstocks, for which the preparation of derivatives chiefly begins with electrophilic substitution reactions or, less frequently, reductions. Their high stability makes them particularly reluctant to participate in cycloadditions under ordinary reaction conditions. Here, we demonstrate exceptional ability 1,3-diaza-2-azoniaallene cations undergo formal (3 + 2) unactivated below room temperature, providing thermally stable dearomatized adducts on a multi-gram scale. The cycloaddition, tolerates polar functional groups, activates ring toward further elaboration. On treatment dienophiles, cycloadducts (4 cycloaddition–cycloreversion cascade yield substituted or fused arenes, including naphthalene derivatives. overall sequence results transmutation arenes through an exchange carbons: two-carbon fragment from original is replaced another incoming dienophile, introducing unconventional disconnection synthesis ubiquitous building blocks. Applications this two-step acenes, isotopically labeled molecules, and medicinally relevant demonstrated.

Язык: Английский

Deuterium in drug discovery: progress, opportunities and challenges DOI Open Access
Rita Maria Concetta Di Martino, Brad D. Maxwell, Tracey Pirali

и другие.

Nature Reviews Drug Discovery, Год журнала: 2023, Номер 22(7), С. 562 - 584

Опубликована: Июнь 5, 2023

Язык: Английский

Процитировано

257

Electrochemical Late-Stage Functionalization DOI Creative Commons
Yulei Wang, Suman Dana, Hao Long

и другие.

Chemical Reviews, Год журнала: 2023, Номер 123(19), С. 11269 - 11335

Опубликована: Сен. 26, 2023

Late-stage functionalization (LSF) constitutes a powerful strategy for the assembly or diversification of novel molecular entities with improved physicochemical biological activities. LSF can thus greatly accelerate development medicinally relevant compounds, crop protecting agents, and functional materials. Electrochemical synthesis has emerged as an environmentally friendly platform transformation organic compounds. Over past decade, electrochemical late-stage (eLSF) gained major momentum, which is summarized herein up to February 2023.

Язык: Английский

Процитировано

146

Radical deuteration DOI
Li Nian, Yantao Li, Xiaopeng Wu

и другие.

Chemical Society Reviews, Год журнала: 2022, Номер 51(15), С. 6291 - 6306

Опубликована: Янв. 1, 2022

This review is a systematic summary of radical deuteration with four reaction types: reductive deuteration, defunctionalization–deuteration, hydrogen–deuterium (H/D) exchange and deuteroalkylation.

Язык: Английский

Процитировано

90

Tandem reductive amination and deuteration over a phosphorus-modified iron center DOI Creative Commons
Haifeng Qi, Yueyue Jiao,

Jianglin Duan

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 21, 2025

Deuterated amines are key building blocks for drug synthesis and the identification of metabolites new pharmaceuticals, which drives search general, efficient, widely applicable methods selective such compounds. Here, we describe a multifunctional phosphorus-doped carbon-supported Fe catalyst with highly dispersed isolated metal sites that allow tandem reductive amination-deuteration sequences. The optimal phosphorus-modified Fe-based shows excellent performance in terms both reactivity regioselectivity wide range deuterated anilines, amines, bioactive complexes, drugs (>50 examples). Experiments on gram scale recycling show application potential this method. Beyond direct applicability developed method, described approach opens perspective development single-atom catalysts other value-adding organic syntheses. play crucial role as identifying novel pharmaceuticals. This study introduces dual-functional iron efficiently enables amination deuteration one-pot process, utilizing H2 reducing agent cost-effective D2O deuterium source.

Язык: Английский

Процитировано

3

Site-Specific and Degree-Controlled Alkyl Deuteration via Cu-Catalyzed Redox-Neutral Deacylation DOI
Xukai Zhou,

Yu Tingting,

Guangbin Dong

и другие.

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(22), С. 9570 - 9575

Опубликована: Май 25, 2022

Deuterated organic compounds have become increasingly important in many areas; however, it remains challenging to install deuterium site-selectively unactivated aliphatic positions with control of the degree deuteration. Here, we report a Cu-catalyzed degree-controlled deacylative deuteration diverse alkyl groups methylketone (acetyl) moiety as traceless activating group. The use N-methylpicolino-hydrazonamide (MPHA) promotes efficient aromatization-driven C–C cleavage. Mono-, di-, and trideuteration at specific sites can be selectively achieved. reaction is redox-neutral broad functional group tolerance. utility this method has been demonstrated forming complete set deuterated ethyl groups, merging Diels–Alder reaction, net devinylative deuteration, synthesis d2-analogue Austedo.

Язык: Английский

Процитировано

57

Chemoselective Decarboxylative Protonation Enabled by Cooperative Earth‐Abundant Element Catalysis DOI
Yen‐Chu Lu, Julian G. West

Angewandte Chemie International Edition, Год журнала: 2022, Номер 62(3)

Опубликована: Ноя. 9, 2022

Decarboxylative protonation is a general deletion tactic to replace polar carboxylic acid groups with hydrogen or its isotope. Current methods rely on the pre-activation of acids, non-sustainable sources, and/or expensive/highly oxidizing photocatalysts, presenting challenges their wide adoption. Here we show that cooperative iron/thiol catalyst system can readily achieve this transformation, hydrodecarboxylating range activated and unactivated acids overcoming scope limitations in previous direct methods. The reaction scaled batch configuration be directly performed deuterated solvent afford high yields d-incorporated products excellent isotope incorporation efficiency; characteristics not attainable photocatalyzed approaches. Preliminary mechanistic studies indicate radical mechanism kinetic results (KIE=1) are consistent light-limited reaction.

Язык: Английский

Процитировано

49

Recent Advances in Deuteration Reactions DOI
Hao Li, Shabbir Muhammad, Wu Li

и другие.

Chinese Journal of Chemistry, Год журнала: 2023, Номер 42(10), С. 1145 - 1156

Опубликована: Дек. 26, 2023

Comprehensive Summary The deuteration of organic compounds has attracted more attentions in recent years for the potential applications new drug discovery and synthetic chemistry. For this purpose, many efficient deuterium labeling methodologies have been developed, including hydrogen isotope exchange (HIE), reductive deuteration, dehalogenative that allow synthesis selectively deuterated compounds. In last few years, great breakthroughs selective achieved interest molecules is rising. review, we summarized developments since 2021. Several types key processes incorporation reactions, H/D exchange, are introduced discussed. Key Scientists 2000s, Derdau Atzrodt's group made contributions to directing assisted noble‐metal catalyzed arenes labeled During same period, Sajiki co‐workers completed a series reactions by heterogeneous platinum‐group metal catalysts. Since 2015, Gregory Pieters developed ruthenium catalysts exchange. 2016, Chirik's presence homogeneous iron complex. David MacMillan coworkers photocatalyzed HIE α‐amino C(sp 3 )–H bonds. From 2020, nanoelectrodes were designed deuterations unactivated unsaturated bonds Zhang's group. Recently, Beller's several strategies isotopic using earth‐abundant Our review latest important

Язык: Английский

Процитировано

32

Ligand‐Enabled Palladium(II)‐Catalyzed Enantioselective β‐C(sp3)−H Arylation of Aliphatic Tertiary Amides** DOI
Chen‐Hui Yuan, Xiaoxia Wang, Lei Jiao

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(17)

Опубликована: Март 5, 2023

Amide is one of the most widespread functional groups in organic and bioorganic chemistry, it would be valuable to achieve stereoselective C(sp3 )-H functionalization amide molecules. Palladium(II) catalysis has been prevalently used C-H activation chemistry past decades, however, due weakly-coordinating feature simple amides, challenging their direct with enantiocontrol by PdII catalysis. Our group developed sulfoxide-2-hydroxypridine (SOHP) ligands, which exhibited remarkable activity Pd-catalyzed C(sp2 activation. In this work, we demonstrate that chiral SOHP ligands served as an ideal solution enantioselective amides. Herein, report efficient asymmetric /SOHP-catalyzed β-C(sp3 arylation aliphatic tertiary ligand plays a key role deprotonation-metalation step.

Язык: Английский

Процитировано

27

Hydrogenative alkene perdeuteration aided by a transient cooperative ligand DOI
Jie Luo, Lijun Lu, Michael Montag

и другие.

Nature Chemistry, Год журнала: 2023, Номер 15(10), С. 1384 - 1390

Опубликована: Сен. 4, 2023

Язык: Английский

Процитировано

27

Metal-free photoinduced hydrogen atom transfer assisted C(sp3)–H thioarylation DOI
Jagrit Grover, Gaurav Prakash, Chitrala Teja

и другие.

Green Chemistry, Год журнала: 2023, Номер 25(9), С. 3431 - 3436

Опубликована: Янв. 1, 2023

A mild metal-free approach for C(sp 3 )–H thioarylation of organic building blocks.

Язык: Английский

Процитировано

25