The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• adduct in more than 4 grams in a total time of 8 hours. The same amount was obtained in batch in a total time of 20 hours. 2 Novel building blocks The scope and limitations of the GBB-3CR have been accurately delineated up to 2018, outlining a comprehensive understanding of its development, observing

• series of novel building blocks, mainly carbonyl derivatives, have been used as starting materials. 2.1 Novel aldehydes Carbonyl compounds are among the most common starting materials for multicomponent reactions: aldehydes play a central role also in the GBB-3CR. Several experiments have demonstrated

• synthesized deoxyuridine-based aldehyde 29 starting from thymidine in 30% yield, according to a known procedure [42]. Then, they tested two different strategies: in the best one (depicted in Scheme 12) 29 was used in the GBB-3CR, then adduct 30 was deacetylated to afford the final product 31 in an overall

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• activities. The most direct way of obtaining this nucleus is the Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR) between aminopyridines, aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis. However, several catalysts for this reaction have major drawbacks such as being

• is known for its chemical and thermal stability. Herein, we report a straightforward approach to the GBB-3CR using HPW as catalyst in ethanol under microwave (μw) heating. This convenient environmentally benign methodology is broad in scope, provides the heterobicyclic products in high yields (up to

• existing ones. Keywords: GBB-3CR; imidazo[1,2-a]pyridine; microwave; phosphotungstic acid; Introduction Imidazo[1,2-a]pyridine is a privileged structure that plays an important role in organic synthesis and in the pharmaceutical industry. This scaffold is present in drugs with several biological

Synthesis of imidazo[1,2-a]pyridine-containing peptidomimetics by tandem of Groebke–Blackburn–Bienaymé and Ugi reactions

• Oleksandr V. Kolomiiets,
• Alexander V. Tsygankov,
• Maryna N. Kornet,
• Aleksander A. Brazhko,
• Vladimir I. Musatov and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2023, 19, 727–735, doi:10.3762/bjoc.19.53

• been described till today: Ugi and Ugi, azido-Ugi and Ugi, Ugi and Passerini, Groebke–Blackburn–Bienaymé (GBB-3CR) and Ugi, GBB-3CR and GBB-3CR, GBB-3CR and Passerini, Orru and Ugi, Orru and Passerini [1] (Scheme 1). However, the issue of whether certain isocyanide multicomponent reactions can be

• peptidomimetic chain was already described in 2010 [32]. Thus, the corresponding acid components were synthesized with GBB-3CR and used in Ugi and Paserini reactions with various aldehydes, amines (for Ugi) and isocyanides. Moreover, in 2016 [33], an alternative route to use GBB-3CR products in Ugi reaction as

• carbonyl component was proposed, but these aldehydes did not have the structure of imidazo[1,2-a]pyridine. Interestingly, in 2019 [1], the synthesis of the amine component using GBB-3CR and the modification of the imidazo-pyrimidine scaffold by a peptidomimetic chain was carried out using the Ugi reaction

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• -based MCRs as the Ugi four-component reaction (Ugi-4CR) and the Groebke–Blackburn–Bienaymé reaction (GBB-3CR) in combination with post-cyclizations are powerful tools to access diversity as well as complexity in a one-pot procedure; in this way they largely cover the available chemical space [9][10][11

• cyclizations [69][70]. There are examples of using aminoazoles as an amine component in GBB-3CR (Scheme 1). They mostly involve different substituted 3-amino-1,2,4-triazoles [71][72][73][74][75] and 2-amino(benzo)thiazoles [71][72][76][77][78][79][80][81][82][83][84][85][86][87][88]. Several publications deal

• -carboxylate are described in GBB-3CR [29][71][83][84][94][95][96]. To the best of our knowledge, there is no information about the reactivity of aminoazoles as an amine component in Ugi-4CR. Taking into account the above-mentioned facts, several aminoazoles, whose reactivity in isocyanide-based reactions had

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

• András Demjén,
• Márió Gyuris,
• János Wölfling,
• László G. Puskás and
• Iván Kanizsai

Beilstein J. Org. Chem. 2014, 10, 2338–2344, doi:10.3762/bjoc.10.243

• -aminoazoles, including thiazole [13][14] and 1,3,4-thiadiazole [15][16] derivatives, or 2-aminoazine-based heterocycles, such as pyridines [17][18][19], pyrimidines [20][21][22][23][24] and pyrazines [25][26][27], have recently been utilized as Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR

• ) inputs (Scheme 1). The transformations of either the 5-aminopyrazoles [28][29], or their 4-substituted ethoxycarbonyl [7][30][31][32] and carbonitrile [28][33][34][35][36] analogues via the GBB-3CR have not been appreciably examined so far. In the relevant literature [7][28][29][31][32][33], the products

• have predominantly been described as 5H-imidazo[1,2-b]pyrazoles with an endo double bond (and not as 1H-imidazo[1,2-b]pyrazoles), but without 2D NMR-based support. However, the GBB-3CR of functionalized pyrazoles might lead to the formation of two regioisomers [24] and four different tautomeric forms