Metalated Indoles, Indazoles, Benzimidazoles, and Azaindoles and Their Synthetic Applications

Abstract

This review focuses on the regioselective metalation of condensed azoles, such as indole, indazole, benzimidazole, 4-, 5-, 6-, and 7-azaindole. The metalation strategies discussed include halogen-metal exchange, metal insertion into carbon-halogen bonds, and directed deprotonation. The influence of different nitrogenprotecting groups and directed metalating groups is discussed. This review covers literature published mainly from 1991 to 2010. 1 Introduction 2 Metalation of Indoles 2.1 C2-Metalation of Indoles 2.2 C3-Metalation of Indoles 2.3 C4-C7-Metalation of Indoles 3 Metalation of Indazoles 4 Metalation of Benzimidazoles 5 Metalation of Azaindoles 6 Conclusion

One-Pot Phosphonylation of Heteroaromatic Lithium Reagents: The Scope and Limitations of Its Use for the Synthesis of Heteroaromatic Phosphonates

“…The usefulness of the direct lithiation of indole followed by phosphonylation of the formed lithium salt has been chosen as a model reaction. As shown previously, lithiation of indole with n -buthyllithium had to be preceded by the suitable protection of the reactive amino group [ 28 ]. The use of t -butoxycarbonyl-( Boc ) protection followed by reaction with trivalent phosphoryl chloride, namely, with 1-chloro- N , N -diisopropyl-1-methoxyphosphinamine, followed by an aqueous work-up, was described as a method for the synthesis of methyl 2-indolyl phosphinate [ 30 ].…”

“…It is well known that electron-rich heterocycles easily undergo direct lithiation at Position 2 when alkyllithium is used. The formed salts are important intermediates in the syntheses of many groups of organic compounds [ 26 , 27 , 28 , 29 ]. Thus, the objective of this paper is to evaluate the scope and limitations of the direct lithiation of heterocyclic compounds, followed by a one-pot reaction with chlorophosphates or chlorophosphites, applied as a method to synthesize heteroaromatic phosphonic acids.…”

Synthesis, Characterization, Solution Behavior and Theoretical Studies of Pd(II) Allyl Complexes with 2-Phenyl-3H-indoles as Ligands

“…Results, presented in Table 2, reveal that the indole ligands 1a-1c are active in the catalytic alkylation of cinnamyl acetate. For t = 24 h the process gave: the linear trans-(E) product (4), the branched derivative (5) and 1-cinnamyl-3-ethyl-2-methylmalonate (6). Under these experimental conditions the conversion varies from 87% (for 1b) to 91% (for 1c), but the presence of compound 6 reduces the effectiveness of the catalytic systems 1a, 1b or 1c and [Pd(η 3 -C 3 H 5 )(µ-Cl)] 2 .…”

“…Indole is one of the most important heterocycles for its presence in bioactive natural products, pharmaceuticals, and agrochemicals [1][2][3][4][5][6][7][8][9]. Indole derivatives are not only "privileged structures" in Medicinal Chemistry [1][2][3][4]6,[10][11][12], due to their biological activity, but also valuable reagents for the design and synthesis of compounds with interesting properties and applications in a variety of fields [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The construction and functionalization of indoles have been studied since long ago; however, and as mentioned by Prof. M. Bandini some years ago "this field had a formidable boom across the new millennium when catalysis started revolutionizing the chemistry of indole" [7].…”

The Azaindole Framework in the Design of Kinase Inhibitors

“…Writing an exhaustive review covering all of the biological activities of azaindole derivatives is virtually impossible. Several reviews exist which have compiled methods leading to these compounds which focused on specific biological activity [21,22,23,24]. To complete these reports, we have voluntary chosen a domain within our research area, the synthesis of kinases inhibitors.…”