Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

Abstract

An efficient sequence based on the Ugi-azide reaction and rhodium(III)-catalyzed intermolecular annulation has been established for the preparation of tetrazole-isoquinolone/pyridone hybrids. Several N-acylaminomethyltetrazoles were reacted with arylacetylenes to form the hybrid products in moderate to very good yields. The method relies on the capacity of the rhodium catalyst to promote C(sp2)–H activation in the presence of a suitable directing group. The Ugi-azide reaction provides broad molecular diversity and enables the introduction of the tetrazole moiety, which may further assist the catalytic reaction by coordinating the metal center. The scope of the isoquinolones is very wide and may be extended to the preparation of complex compounds having heterocyclic moieties such as pyridone, furan, thiophene and pyrrole, as well as the corresponding benzo-fused derivatives. The developed procedure is simple, reproducible and does not require inert conditions.

Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs

“…However, the discovery of new multicomponent reactions is an active research field [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], with novel exciting MCRs being discovered and incorporated to the synthetic armamentarium every year. Among these MCRs with transition metal catalysis [ 28 , 29 , 30 , 31 , 32 , 33 , 34 ], radical process [ 7 , 21 , 35 , 36 ] and organo-catalysis [ 37 , 38 , 39 , 40 , 41 ] should also be mentioned.…”

Advances in Tetrazole Synthesis – An Overview

“…Nanocrystalline metal oxides are found as efficient gas absorbents and also for the destruction of toxic chemicals; [21] moreover, they can also be used as catalysts for organic transformations like benzylation [22] epoxidation. [23] In the past decade, multicomponent reactions [24,25] have been developed to synthesize biologically active compounds, and the process has become crucial in organic and medicinal chemistry research. [26] The need to develop various processes is due to the extensive application of tetrazoles in medicinal chemistry.…”

A One-Pot Six-Component Reaction for the Synthesis of 1,5-Disubstituted Tetrazol-1,2,3-Triazole Hybrids and Their Cytotoxic Activity against the MCF-7 Cell Line

“…Among this group of MCRs, the Ugi-azide reaction undoubtedly occupies a relevant place in the synthetic landscape where the generation of 1,5-DS-T libraries becomes promising. It allows the fast, diverse, and efficient generation of series of compounds, which is further demonstrated by the synthesis of various hybrid systems containing 1,5-DS-T moiety, such as triazole-tetrazole 1 [25], phenylamino pyrimidine-tetrazole 2 [26], imidazole-tetrazole (3) [27], indole-tetrazole 4 [28], imidazol [1,2-a]pyridine-tetrazole 5 [29], and isoquinolone/pyridone-tetrazole 6 [30] (Figure 1).…”

“…Among this group of MCRs, the Ugi-azide reaction undoubtedly occupies a relevant place in the synthetic landscape where the generation of 1,5-DS-T libraries becomes promising. It allows the fast, diverse, and efficient generation of series of compounds, which is further demonstrated by the synthesis of various hybrid systems containing 1,5-DS-T moiety, such as triazole-tetrazole 1 [25], phenylamino pyrimidine-tetrazole 2 [26], imidazole-tetrazole (3) [27], indole-tetrazole 4 [28], imidazol [1,2-a]pyridinetetrazole 5 [29], and isoquinolone/pyridone-tetrazole 6 [30] (Figure 1). In a previous work, we described a synthetic strategy for obtaining a series of 1,5-DS-T hybrid compounds linked to 1,2,3-triazoles in a two-step reaction process by the Ugiazide reaction, followed by copper-catalyzed azide cycloaddition (CuAAC) as a post-condensation reaction, describing a reaction of its type for the first time in an Ugi-azide process [25].…”