Interrupted Pyridine Hydrogenation: Asymmetric Synthesis of δ‐Lactams DOI

Tobias Wagener,

Lukas Lückemeier,

Constantin G. Daniliuc

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(12), P. 6425 - 6429

Published: Jan. 18, 2021

Abstract Metal‐catalyzed hydrogenation is an effective method to transform readily available arenes into saturated motifs, however, current strategies are limited the formation of C−H and N−H bonds. The stepwise addition hydrogen yields reactive unsaturated intermediates that rapidly reduced. In contrast, interruption complete by further functionalization offers great potential for increasing chemical complexity in a single reaction step. Overcoming tenet full reduction arene has been seldom demonstrated. this work we report synthesis sought‐after, enantioenriched δ‐lactams from oxazolidinone‐substituted pyridines water interrupted mechanism.

Language: Английский

Dearomative Photocatalytic Construction of Bridged 1,3‐Diazepanes DOI
Jamie A. Leitch, Tatiana Rogova, Fernanda Duarte

et al.

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(10), P. 4121 - 4130

Published: Jan. 8, 2020

Abstract The construction of diverse sp 3 ‐rich skeletal ring systems is importance to drug discovery programmes and natural product synthesis. Herein, we report the photocatalytic 2,7‐diazabicyclo[3.2.1]octanes (bridged 1,3‐diazepanes) via a reductive diversion Minisci reaction. fused tricyclic proposed form radical addition C4 position 4‐substituted quinoline substrates, with subsequent Hantzsch ester‐promoted reduction dihydropyridine intermediate which undergoes in situ two‐electron closure bridged diazepane architecture. A wide scope N‐arylimine derivatives was demonstrated good efficiency observed sterically congested all‐carbon quaternary centers. Computational experimental mechanistic studies provided insights into reaction mechanism regioselectivity/diastereoselectivity.

Language: Английский

Citations

72
Fluorinated Rings: Conformation and Application DOI
Rajarshi Mondal,

Mohamed Agbaria,

Zackaria Nairoukh

et al.

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(25), P. 7193 - 7213

Published: Jan. 29, 2021

The introduction of fluorine atoms into molecules and materials across many fields academic industrial research is now commonplace, owing to their unique properties. A particularly interesting feature the impact substitution on relative orientation a C-F bond when incorporated organic molecules. In this Review, we will be discussing conformational behavior fluorinated aliphatic carbo- heterocyclic systems. preference each system associated with various interactions introduced by such as charge-dipole, dipole-dipole, hyperconjugative interactions. contribution interaction stabilization alicyclic system, which manifests itself in low conformations, discussed detail. novelty demonstrated presenting most recent applications.

Language: Английский

Citations

66
Recent Advances in the Domain of Cyclic (Alkyl)(Amino) Carbenes DOI Creative Commons
Saroj Kumar Kushvaha, Ankush Mishra, Herbert W. Roesky

et al.

Chemistry - An Asian Journal, Journal Year: 2022, Volume and Issue: 17(7)

Published: Jan. 6, 2022

Isolation of cyclic (alkyl) amino carbenes (cAACs) in 2005 has been a major achievement the field stable due to their better electronic properties. cAACs and bicyclic(alkyl)(amino)carbene (BicAAC) essence are most electrophilic as well nucleophilic known till date. Due excellent properties terms character, have utilized different areas chemistry, including stabilization low valent main group transition metal species, activation small molecules, catalysis. The applications catalysis opened up new avenues research cAAC chemistry. This review summarizes results chemistry published until August 2021.

Language: Английский

Citations

66
Recent developments in enantio- and diastereoselective hydrogenation of N-heteroaromatic compounds DOI Creative Commons
Gunasekar Ramachandran, Ross L. Goodyear, Ilaria Proietti Silvestri

et al.

Organic & Biomolecular Chemistry, Journal Year: 2022, Volume and Issue: 20(9), P. 1794 - 1827

Published: Jan. 1, 2022

The enantioselective and diastereoselective hydrogenation of N-heteroaromatic compounds is an efficient strategy to access chirally enriched cyclic heterocycles, which often possess highly bio-active properties. This strategy, however, has only been established in recent times. part due the challenges high stability aromatic presence heteroatoms that have potential poison chiral catalysts. Additionally, are a structurally diverse family substrates, each group showing distinct reactivity hydrogenation. Advances years allowed various compounds, including pyridines, indoles, quinolines, isoquinolines, quinoxalines imidazoles, be hydrogenated with good excellent enantioselectivity under appropriate reaction conditions. Transition-metal catalysis, utilising iridium, ruthenium, rhodium, palladium complexes, found play important role this field. More recently, organocatalysis shown for certain compounds. review provides analysis developments importance these molecules their applications drug discovery highlighted throughout review.

Language: Английский

Citations

59
Modular access to substituted cyclohexanes with kinetic stereocontrol DOI
Yangyang Li, Yuqiang Li, Hongjin Shi

et al.

Science, Journal Year: 2022, Volume and Issue: 376(6594), P. 749 - 753

Published: May 12, 2022

Substituted six-membered cyclic hydrocarbons are common constituents of biologically active compounds. Although methods for the synthesis thermodynamically favored, disubstituted cyclohexanes well established, a reliable and modular protocol their stereoisomers is still elusive. Herein, we report general strategy with excellent kinetic stereocontrol from readily accessible substituted methylenecyclohexanes by implementation chain-walking catalysis. Mechanistically, initial introduction sterically demanding boron ester group adjacent to cyclohexane key guiding stereochemical outcome. The synthetic potential this methodology has been highlighted in late-stage modification complex bioactive molecules comparison current cross-coupling techniques.

Language: Английский

Citations

57
Chromium-catalyzed stereodivergent E- and Z-selective alkyne hydrogenation controlled by cyclic (alkyl)(amino)carbene ligands DOI Creative Commons
Liang Ling, Chenyang Hu, Linhong Long

et al.

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

Published: Feb. 22, 2023

Abstract The hydrogenation of alkynes allows the synthesis olefins, which are important feedstock for materials, pharmaceutical, and petrochemical industry. Thus, methods that enable this transformation via low-cost metal catalysis desirable. However, achieving stereochemical control in reaction is a long-standing challenge. Here, we report on chromium-catalyzed E - Z -selective olefin alkynes, controlled by two carbene ligands. A cyclic (alkyl)(amino)carbene ligand contains phosphino anchor enables trans -addition manner, selectively forming -olefins. With an imino anchor-incorporated ligand, stereoselectivity can be switched, giving mainly -isomers. This ligand-enabled geometrical stereoinversion strategy one overrides common -selectivity with different catalysis, allowing highly efficient on-demand access to both -olefins stereo-complementary fashion. Mechanistic studies indicate steric effect between these ligands may dominate selective or stereochemistry.

Language: Английский

Citations

28
Oxidative Dearomatization of Pyridines DOI

Zohaib Siddiqi,

Tanner W. Bingham, Tsukasa Shimakawa

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2358 - 2363

Published: Jan. 17, 2024

Dearomatization of pyridines is a well-established synthetic approach to access piperidines. Although remarkably powerful, existing dearomatization processes have been limited the hydrogenation or addition carbon-based nucleophiles activated pyridiniums. Here, we show that arenophile-mediated dearomatizations can be applied directly introduce heteroatom functionalities without prior substrate activation. The arenophile platform in combination with olefin oxidation chemistry provides dihydropyridine cis-diols and epoxides. These previously elusive compounds are now readily accessible used for downstream preparation diversely functionalized

Language: Английский

Citations

14
Visible-Light Photocatalytic C–H Amination of Arenes Utilizing Acridine–Lewis Acid Complexes DOI
Matthew R. Lasky,

En‐Chih Liu,

Matthew S. Remy

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(21), P. 14799 - 14806

Published: May 17, 2024

This report describes the development of a visible-light photocatalytic system for C(sp2)–H amination that leverages in situ-generated photocatalysts. We demonstrate combination acridine derivatives and Lewis acids forms potent photooxidants promote C–H electronically diverse arenes upon irradiation with (440 nm). A first-generation photocatalyst composed Sc(OTf)3 effects substrates oxidation potentials ≤ +2.5 V vs SCE pyrazole, triazole, pyridine nucleophiles. Furthermore, simplicity modularity this enable variation both acid to tune reactivity. enabled rapid identification two second-generation photocatalysts (derived from (i) Al(OTf)3 or (ii) pyridinium-substituted acridine) catalyze particularly challenging transformation: benzene as limiting reagent.

Language: Английский

Citations

10
Selective 1,4-syn-Addition to Cyclic 1,3-Dienes via Hybrid Palladium Catalysis DOI Creative Commons
Yan Liang,

Tiancen Bian,

Komal Yadav

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(6), P. 1191 - 1200

Published: May 15, 2024

1,4-cis-Disubstituted cyclic compounds play a pivotal role in pharmaceutical development, offering enhanced potency and bioavailability. However, their stereoselective modular synthesis remains long-standing challenge. Here, we report an innovative strategy for accessing these structures via mild conditions employing 1,3-dienes/alkyl(aryl)halides amines. This procedure exhibits wide substrate scope that tolerates various functional groups. The utility of this method is demonstrated the efficient TRPV6 inhibitor, CFTR modulator, other bioactive molecules. Combined experimental computational studies suggest hybrid palladium-catalyzed radical-polar crossover mechanism crucial achieving exceptional 1,4-syn-addition selectivity (dr > 20:1).

Language: Английский

Citations

9
Hydrogenation of N-Heteroarenes Using Rhodium Precatalysts: Reductive Elimination Leads to Formation of Multimetallic Clusters DOI
Sangmin Kim, Florian Loose, Máté J. Bezdek

et al.

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(44), P. 17900 - 17908

Published: Oct. 7, 2019

A rhodium-catalyzed method for the hydrogenation of N-heteroarenes is described. diverse array unsubstituted including pyridine, pyrrole, and pyrazine, traditionally challenging substrates hydrogenation, were successfully hydrogenated using organometallic precatalysts, [(η5-C5Me5)Rh(N-C)H] (N-C = 2-phenylpyridinyl (ppy) or benzo[h]quinolinyl (bq)). In addition, polyaromatic exhibited uncommon chemoselectivity. Studies into catalyst activation revealed that photochemical thermal [(η5-C5Me5)Rh(bq)H] induced C(sp2)-H reductive elimination generated bimetallic complex, [(η5-C5Me5)Rh(μ2,η2-bq)Rh(η5-C5Me5)H]. presence H2, both precursors [(η5-C5Me5)Rh(μ2,η2-bq)Rh(η5-C5Me5)H] converted to a pentametallic rhodium hydride cluster, [(η5-C5Me5)4Rh5H7], structure which was established by NMR spectroscopy, X-ray diffraction, neutron diffraction. Kinetic studies on pyridine conducted with each isolated complexes identify catalytically relevant species. The data are most consistent catalysis prompted an unobserved multimetallic cluster formation [(η5-C5Me5)4Rh5H7] serving as deactivation pathway.

Language: Английский

Citations

73