The regioselective functionalization of 7-azaindole by controlled annular isomerism employing a directed metalation-group migration is reported. The N7 carbamoyl azaindoles undergo regioselective metalation and quenching with an electrophile to furnish C6-substituted derivatives which, in the presence of a catalytic amount of ClCONR promotes a carbamoyl group shift or dance from N7 to N1. A second directed metalation/electrophile quench sequence leads to 2,6-substituted azaindoles. Optimization of the metalation conditions for C2 and C6, separately and iteratively, is presented. Using the directed metalation group dance strategy, a late-stage deuteration of an antipsychotic drug is described. Overall, the controlled migration of the carbamoyl directing group allows multiple functionalization events of the bioactive azaindole scaffold.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/anie.201901724 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Brønsted Acid-Catalyzed Regioselective Coupling between Azoles and Arylcyclobutenes.
Chem Asian J
January 2025
Northwest University, Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Department of Chemistry & Materials Science,, 1 Xuefu Ave., Guodu Education and Hi-Tech Industries Zone,, Chang'an District, 710127, Xi'an, CHINA.
Herein, we describe a protocol for Brønsted acid-catalyzed regioselective coupling of azoles such as pyrazoles, 1,2,3-triazole, 1,3,4-triazole, benzotriazole, indazole and tetrazole, to cyclobutenes. These azoles could be directly coupled with various arylcyclobutenes with high site-selectivity, offering a distinct entry to more functionalized cyclobutanes. The usage of inexpensive TsOH•H2O catalyst, broad substrate scope, and open-air conditions make this protocol practically viable.
View Article and Find Full Text PDFManganese(III)-Mediated Selective Cascade Phosphorylation-Cyclization of Tertiary Enamides for the Synthesis of Multi-Substituted 3-Phosphorylpyridines.
J Org Chem
January 2025
School of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, China.
A novel regioselective manganese(III)-mediated radical cascade cyclization of N-propargyl enamides with various H-phosphine oxides, H-phosphinates and H-phosphonates was developed. Mechanistic studies show that the reaction is mainly composed of the selective addition of phosphonyl radical to C≡C bond and the intramolecular 6--trig cyclization of vinyl radical. Utilizing this protocol, we successfully synthesized a diverse range of 3-phosphorylpyridines in high efficiency with good functional group compatibility and simple operation.
View Article and Find Full Text PDFRhodium-mediated Assembly of New Heterocycles: From Borylenes to Oxaboroles.
Angew Chem Int Ed Engl
January 2025
University of Lethbridge, Chemistry and Biochemistry, CANADA.
Base-stabilized rhodium borylene complex κ2-L(CO)Rh(BMes), 2; κ2-L = κ2-NN'-Rh,κ1-N-B-(2,5-[iPr2P=N(4-iPrC6H4)]2-N'(C4H2)-); Mes = mesityl, reacts with a series of alkynes (PhC≡C-R; R = Ph, Me, CO2Et, H) to yield unique structures whereby the alkyne has regioselectively added across boron and the carbon atom of a CO ligand. The resulting complexes, LRh[C(O)C(Ph)C(R)B(Mes)], 3R, react with additional CO to afford cycle-containing products, L(CO)Rh([[EQUATION]]), 5R, that ultimately release highly functionalized organic heterocycles of the form [[EQUATION]]=NPipp (Pipp = 4-iPrC6H4), 6. These oxaboroles, which were assembled from a primary hydroborane, CO, an alkyne, and an azide-generated NPipp, are structurally analogous to two of the five boron-containing therapeutics approved by the FDA.
View Article and Find Full Text PDFIndoloindolizines: The Complete Story of a Polycyclic Aromatic Scaffold from Theoretical Design to Organic Field-Effect Transistor Applications.
J Am Chem Soc
January 2025
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
The development of stable and tunable polycyclic aromatic compounds (PACs) is crucial for the advancement of organic optoelectronics. Conventional PACs, such as acenes, often suffer from poor stability due to photooxidation and oligomerization, which are linked to their frontier molecular orbital energy levels. To address these limitations, we designed and synthesized a new class of π-expanded indoloindolizines by merging indole and indolizine moieties into a single polycyclic framework.
View Article and Find Full Text PDFZero-Valent Copper Catalysis Enables Regio- and Stereoselective Difunctionalization of Alkynes.
Angew Chem Int Ed Engl
January 2025
Jain University - Ramanagara Campus, Centre for Nano and Material Sciences, Jakkasandra Post Kanakapura Taluk, Ramanagara-562112, Bangalore, 562112, Bangalore, INDIA.
The development of a metallic copper-based catalyst system remains a significant challenge. Herein, we report the synthesis of highly stable, active, and reusable Cu0 catalyst for the carboboration of alkynes using carbon electrophiles and bis(pinacolato)diboron (B2pin2) as chemical feedstocks to afford di- and trisubstituted vinylboronate esters in a regio- and stereoselective manner with appreciable turnover number (TON) of up to 2535 under mild reaction conditions. This three-component coupling reaction works well with a variety of substituted electrophiles and alkynes with broad functional group tolerance.
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!