One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• and Heck cyclization reactions. The integration of the multicomponent and post-condensation reactions in one-pot maximizes the pot-, atom-, and step-economy (PASE). Keywords: Heck reaction; one-pot; tetrahydroisoquinoline; tetrazolo-pyrazino[2,1-a]isoquinolin-6(5H)-ones; tetrazole; Ugi-azide reaction

• ]quinazolines (Scheme 2D) [40]. There are numbers of Ugi and subsequential Heck (or reductive Heck) reactions that have been developed for the synthesis of poly-heterocyclic compounds [43][44][45][46][47][48][49][50][51]. Reported in this paper is a one-pot Ugi-azide reaction followed by an intramolecular Heck

• reaction for the synthesis of tetrazolyl-1,2,3,4-tetrahydroisoquinoline scaffolds 6 and 8 (Scheme 3). The first step is the Ugi-azide reaction of a 2-bromobenzoaldehyde 1, allylamine hydrochloride (2), azidotrimethylsilane (TMSN3, 3), and an isocyanide 4 affording tetrazoles 5. If ethyl isocyanoacetate is

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• release of a nitrogen molecule to form the desired product 46. In 2018, Ding and co-workers reported the synthesis of 2-tetrazolyl-substituted 3-acylpyrroles 53 via sequential Ugi-azide/Ag-catalyzed oxidative cycloisomerization reactions in good yield (Scheme 20) [64]. Firstly, The Ugi-azide reaction

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• standard Ugi–azide reaction conditions [35][36][37][38][39] in a one-pot, tandem process. Subjecting glucose-derived lactam 1 to such a procedure gave the desired product in good yield, but with virtually no diastereoselectivity, as shown in Scheme 2. Optimization and scope An initial optimization study

• highest yield and diastereoselectivity, thus were chosen as optimal (Table 1, entry 9.). We also tried to isolate the imine after the reduction step and carry out the second step in a solvent commonly used for the Ugi–azide reaction alone. For this, we observed a significant decrease in overall yield and

• Ugi–azide reaction variant described in this work. We suppose that after reduction of amide I by Schwartz’s reagent, complex II undergoes a slow, spontaneous decomposition, yielding imine III. III then reacts with TMSN3, which acts as both, an imine activator and an azide anion source. Complex IV

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

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• Natural Product Research, Faculty of Chemistry, University of Havana, Zapata y G, 10400, La Habana, Cuba Peoples´ Friendship University of Russia (RUDN University) Miklukho-Maklaya Street 6, 117198 Moscow, Russia 10.3762/bjoc.15.237 Abstract An efficient sequence based on the Ugi-azide reaction and

• 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

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• 10 amino acid residues [64]. As shown in Scheme 18, the procedure comprised the growth of the antimicrobial peptide sequence 60 followed by the multicomponent incorporation of cholestanic steroids functionalized as isocyanide component. Two related on-resin Ugi-4CRs were employed, i.e., the Ugi-azide

• reaction based on hydrazoic acid as acid component that furnished peptide-steroid 61 and the classic one using acetic acid as carboxylic acid component, which led to conjugate 62. These protocols enabled the introduction not only of a steroidal moiety at the N-terminus but also of lipid and affinity tags

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• bis(1,5-disubstituted tetrazoles). Methyl isocyanoacetate 13a was used as an essential component in the first hydrazino-Ugi-azide reaction allowing consecutive Ugi reactions to take place. In the first step, 13a, hydrazides, aldehyde or ketone, trimethylsilyl azide (TMSN3) and ZnCl2 (10 mol %) in

• corresponding hydrazides 15, which were used in a second hydrazine-Ugi-azide reaction with various ketones, to obtain the acylhydrazino bis(1,5-disubstituted tetrazoles) 16 in yields ranging from 45–70%. Consecutive Ugi reactions for the synthesis of substituted α-aminomethyl tetrazoles have also been described

• isocyanide-based multicomponent reactions in the synthesis of macrocycles containing a tetrazole nucleus [30]. The strategy was based on the use of α-isocyano-ω-carboxylic esters 71 via a microwave-mediated Ugi-azide reaction at the beginning of the synthesis and an intramolecular Ugi reaction of

Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256

• bearing 1,5-disubstituted tetrazoles. Our strategy was accomplished in only three steps: first, a one-pot hydrazino-Ugi-azide four-component reaction; second a hydrazinolysis and finally an additional hydrazino-Ugi-azide reaction. This sequence provides the title compounds in moderate to excellent yields

• ); Ugi-azide reaction; Introduction Tetrazoles are extensively studied, useful non-natural heterocyclic skeletons with the highest nitrogen content among the stable heterocycles [1][2]. The tetrazole-ring system has a variety of applications in organic chemistry, coordination chemistry, and agriculture

• different approach focused on their postcyclization strategy [32]. Results and Discussion Two multicomponent reactions were used for the synthesis of acylhydrazino bis(1,5-disubstituted tetrazoles) as outlined in Scheme 1. The approach presented here is initially based on a hydrazino-Ugi-azide reaction

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

•  48). In a combined approach, Gunawan et al. also described such an Ugi-azide reaction to develop γ/δ/ε-lactam tetrazoles [126][127]. Depending on the keto-ester or acid used, an Ugi reaction with different primary amines, isocyanides and TMSN3 followed by subsequent cyclization gave either γ-, δ- or