Redox Active vs Redox Neutral in Ru/Pd-Catalyzed Sulfonylation: Theoretical Insights into Structure–Activity Relationship between Metal Centers and Regio-Selectivity DOI
Qingqing Lin,

Huan Lv,

Lu Yu

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(24), P. 18131 - 18141

Published: Dec. 10, 2024

The structure-activity relationship between the metal center and regio-selectivity is persistently a pivotal scientific issue. To address this, we select 2-phenylpyridine sulfonylation reactions catalyzed by ruthenium palladium as research subjects. An extensive theoretical study has been conducted on their reaction mechanisms, sources of regio-selectivity, evolution electronic structures. distinct structures lead to completely different catalytic mechanisms structure processes for palladium. Ruthenium tends form six-coordinate octahedral complexes, thus undergoing an inner-sphere redox active Ru(II)-Ru(III)-Ru(IV)-Ru(II) cycle. In contrast, four-coordinate planar quadrilateral hence outer-sphere neutral Pd(II) fundamentally differentiate radical attack modes in sulfonation process, thereby determining reaction. Ru-catalyzed system, meta-selectivity arises mainly from more stable Schrock carbene-type meta-intermediate. For Pd-catalyzed ortho-selectivity comes stabilizing effect single electron. This provides novel insights into how centers influences mechanism selectivity, making contribution deeper comprehension underlying aromatic functionalization reactions.

Language: Английский

Late-stage meta-C–H alkylation of pharmaceuticals to modulate biological properties and expedite molecular optimisation in a single step DOI Creative Commons
Lucas Guillemard, Lutz Ackermann, Magnus J. Johansson

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 18, 2024

Catalysed C-H activation has emerged as a transformative platform for molecular synthesis and provides new opportunities in drug discovery by late-stage functionalisation (LSF) of complex molecules. Notably, small aliphatic motifs have gained significant interest medicinal chemistry their beneficial properties applications sp

Language: Английский

Citations

13
Unlocking regioselective meta-alkylation with epoxides and oxetanes via dynamic kinetic catalyst control DOI Creative Commons

Peng‐Bo Bai,

Alastair J. Durie, Gang‐Wei Wang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 2, 2024

Abstract Regioselective arene C−H bond alkylation is a powerful tool in synthetic chemistry, yet subject to many challenges. Herein, we report the meta -C−H of aromatics bearing N -directing groups using (hetero)aromatic epoxides as alkylating agents. This method results complete regioselectivity on both well epoxide coupling partners, cleaving exclusively benzylic C−O bond. Oxetanes, which are normally unreactive, also participate reagents under reaction conditions. Our mechanistic studies reveal an unexpected reversible ring opening process undergoing catalyst-controlled regioselection, key for observed high regioselectivities.

Language: Английский

Citations

8
Visible-Light-Mediated Ruthenium-Catalyzed para-Selective Alkylation of Unprotected Anilines DOI
Xinyan Lv,

Yaohang Cheng,

Yingxiao Zong

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(11), P. 7310 - 7321

Published: May 15, 2023

Anilines are important moieties in organic chemistry, pharmaceuticals, and materials science. Although para-selective functionalization of anilides tertiary anilines is well established, unprotected have posed a challenge. Herein, we report visible-light-mediated Ru(II)-catalyzed para-alkylation anilines. The distinct Ru(II)–aniline complex enabled the reaction to proceed with extremely high efficiency (2 h) under mild conditions. good functional group tolerance allowed late-stage even aggregation-induced emission luminogen labeling natural products drugs. A mechanistic investigation suggests that crucial for both triggering controlling para-selectivity.

Language: Английский

Citations

14
Ruthenium-Catalyzed Difunctionalization of Vinyl Cyclopropanes for Double m-C(sp2)–H/C-5(sp3)–H Functionalization DOI

Yu‐Yong Luan,

Jinye Li,

Wei‐Yu Shi

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(15), P. 3213 - 3217

Published: April 4, 2024

With in-depth research on 1,2-difunctionalization, remote difunctionalization has garnered widespread attention for achieving multifunctionality. Herein, we report a strategy under mild conditions. This exhibited good substrate suitability and functional group tolerance. In addition, the significance of this method is further evidenced by its successful application in scaling up conducting additional transformations target compounds. Mechanistic studies showed that radical might be involved process.

Language: Английский

Citations

5
Precision installation of silyl synthetic handles within arenes by regiocontrolled ruthenium C(sp2)–H functionalization DOI Creative Commons
Jamie H. Docherty, Mishra Deepak Hareram, Luke M. Nichols

et al.

Nature Catalysis, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Abstract The site-selective functionalization of C( sp 2 )–H bonds represents a powerful strategy for the synthesis structurally diverse compounds with broad applicability. Here we report efficient regioselective catalytic methods formation benzyltrimethylsilanes through ruthenium-catalysed silylmethylation. developed protocols enable selective at both ortho and meta positions within arenes bearing N-based directing groups. resulting silylmethyl can undergo transformations, including nucleophilic aromatic substitution, carbonyl addition, olefination desilylation. Significantly, regiodivergent installation synthetic handles allows pharmaceutical losmapimod could further be applied in direct late-stage functionalizations. Mechanistically, an essential role biscyclometallated ruthenium(II) species has been found, intermediate ruthenium(III) indicated by paramagnetic NMR experiments. These inventions mechanistic elucidations signify transformative step functionalization, enabling syntheses providing framework future development.

Language: Английский

Citations

0
Ruthenium(II)‐Catalyzed Late‐Stage Incorporation of N‐Aryl Triazoles and Tetrazoles with Sulfonium Salts via C−H Activation DOI Creative Commons
Hendrik Simon, Agnese Zangarelli,

Tristan Bauch

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(26)

Published: April 15, 2024

The late-stage functionalization of active pharmaceutical ingredients is a key challenge in medicinal chemistry. Furthermore, N-aryl triazoles and tetrazoles are important structural motifs with the potential to boost activity diverse drug molecules. Using easily accessible dibenzothiophenium salts for ruthenium-catalyzed C-H arylation, these scaffolds were introduced into variety bioactive compounds. Our methodology uses cost-efficient ruthenium, KOAc as mild base gives access plethora highly decorated triazole tetrazole containing derivatives.

Language: Английский

Citations

3
Integrating a multitask graph neural network with DFT calculations for site-selectivity prediction of arenes and mechanistic knowledge generation DOI Creative Commons
Xinran Chen, Zijing Zhang, Xin Hong

et al.

Nature Synthesis, Journal Year: 2025, Volume and Issue: unknown

Published: April 7, 2025

Language: Английский

Citations

0
Plausible PEPPSI catalysts for direct C-H functionalization of furans and pyrroles DOI

Naima Munir,

Nevın Gürbüz,

M. Naveed Zafar

et al.

Journal of Molecular Structure, Journal Year: 2023, Volume and Issue: 1295, P. 136679 - 136679

Published: Sept. 19, 2023

Language: Английский

Citations

6
Ruthenaphoto-catalyzed ortho-C−H alkylation with secondary alkyl halides: SET-enabled ruthenium(II/III/IV) manifold DOI Creative Commons
Yulei Wang, Binbin Yuan,

Xuexue Chang

et al.

Chem, Journal Year: 2024, Volume and Issue: unknown, P. 102387 - 102387

Published: Dec. 1, 2024

Language: Английский

Citations

1
DLPNO-CCSD(T) and DFT study of the acetate-assisted C–H activation of benzaldimine at [RuCl2(p-cymene)]2: the relevance of ligand exchange processes at ruthenium(ii) complexes in polar protic media DOI Creative Commons
Vicente Ojea, Marı́a Ruiz

Dalton Transactions, Journal Year: 2024, Volume and Issue: 53(20), P. 8662 - 8679

Published: Jan. 1, 2024

For acetate-assisted cyclometallation of benzaldimine at [RuCl 2 ( p -cymene)] in MeOH, anion dissociation is the rate-determining step. Subsequent C–H bond activation events and acetate/chloride exchange cycloruthenate are reversible processes.

Language: Английский

Citations

1