Direct asymmetric functionalization of the pyridyl C-H bond represents a longstanding challenge in organic chemistry. We herein describe the first enantioselective -C-H activation of pyridines through the use of a Ni-Al bimetallic catalyst system and N-heterocyclic carbene (NHC) ligand for intermolecular hydroarylation of styrenes. The reaction procceds in high to excellent enantioselectivities (up to 98.5:1.5 er) and high site-selectivities for both styrene and pyridine components (up to >98:2). Consequently, a broad range of enantioenriched 1,1-diarylalkanes containing pyridine moieties could be prepared in a single step with 100% atom economy. Computational studies supported a mechanism involving a ligand-to-ligand H-transfer (LLHT) and reductive elimination sequence, with LLHT being the rate- and enantioselectivity-determining step. DFT studies indicate that the π-π stacking interaction between the NHC aryl fragment and trans-styrenes is critical for high reactivity and enantiocontrol.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jacs.2c04043 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Intermediate Control: Unlocking Hitherto Unknown Reactivity and Selectivity in N-Conjugated Allenes and Alkynes.
Acc Chem Res
January 2025
Department of Chemistry and Chemistry Institution for Functional Materials, Pusan National University, Busan 46241, Republic of Korea.
ConspectusControlling selectivity through manipulation of reaction intermediates remains one of the most enduring challenges in organic chemistry, providing novel solutions for selective C-C π-bond functionalization. This approach, guided by activation principles, provides an effective method for selective functional group installation, enabling direct synthesis of organic molecules that are inaccessible through conventional pathways. In particular, the selective functionalization of N-conjugated allenes and alkynes has emerged as a promising research focus, driven by advances in controlling reactive intermediates and activation strategies.
View Article and Find Full Text PDFA selective photoinduced radical -alkenylation of phenols and naphthols with terminal alkynes.
Chem Commun (Camb)
September 2024
Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram 695019, Kerala, India.
The visible light-promoted -alkenylation of phenols and naphthols with terminal alkynes is achieved using 2,4,6-tris(4-fluorophenyl)pyrylium tetrafluoroborate (T(-F)PPT) as a photocatalyst at room temperature without the need of any external ligand or additive. Apart from its excellent functional group tolerance, the protocol described herein represents an appealing alternative strategy to classical transition-metal catalysed hydroarylation reactions. Mechanistic investigations revealed that the reaction involves a radical pathway.
View Article and Find Full Text PDFPhotoinduced Intermolecular Radical Hydroalkylation of Olefins via Ligated Boryl Radicals-Mediated Halogen Atom Transfer.
Org Lett
July 2024
Flow Chemistry Group, van't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, 1098 XH Amsterdam, The Netherlands.
Light-mediated Halogen-Atom Transfer (XAT) has become a significant methodology in contemporary synthesis. Unlike α-aminoalkyl and silyl radicals, ligated boryl radicals (LBRs) have not been extensively explored as halogen atom abstractors. In this study, we introduce NHC-ligated boranes as optimal radical chain carriers for the intermolecular reductive radical hydroalkylation and hydroarylation of electron-deficient olefins by using direct UV-A light irradiation.
View Article and Find Full Text PDFLigand Effects in Carboxylic Ester- and Aldehyde-Assisted β-C-H Activation in Regiodivergent and Enantioselective Cycloisomerization-Hydroalkenylation and Cycloisomerization-Hydroarylation, and [2 + 2 + 2]-Cycloadditions of 1,6-Enynes.
J Am Chem Soc
July 2024
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.
Herein, we report room temperature, atom-economic protocols for high regio- and enantioselective tandem cycloisomerization-hydroarylation and cycloisomerization-hydroalkenylation of 1,6-enynes leading to vicinal -functionalized pyrrolidines, tetrahydrofurans, and cyclopentanes. The latter steps in these processes involve carbonyl-coordination-assisted C-H activation of aromatic aldehydes and esters, and, a similar, yet rarely seen, β-C-H activation in the case of the acrylates. Synthetically useful enantioselective versions of such reactions are rare and are limited to the C-H activation of indoles and pyrroles.
View Article and Find Full Text PDFSynthesis of Benzo[]carbazoles and Dibenzo[,]carbazoles via Sequential Gold Catalysis and Photomediated Cyclization.
J Org Chem
June 2024
College of Chemistry, Jilin University, Changchun 130012, Jilin, P. R. China.
Herein, we report a reaction protocol for the construction of benzo[]carbazole and dibenzo[,]carbazole frameworks. The detailed gold catalytic reaction conditions developed for the challenging intermolecular carbon nucleophilic addition to internal alkynes are realized, giving the desired alkyne hydroarylation products in good yields. The resulting trisubstituted alkenes are able to undergo photomediated cyclization, furnishing the desired carbazole molecules with excellent yields and high efficiency.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!