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

• reactions in hands, we next evaluated the substrate scope by synthesizing 11 derivatives (Scheme 4) using nine benzaldehydes 1, two isonitriles or ethyl isocyanoacetate 4, allylamine hydrochloride (2), and trimethylsilyl azide (3) for the initial Ugi-azide reaction. Among them, products 6a and 6b from the

• reaction of isonitriles were synthesized in moderate yields (58–60%). For the Ugi reaction involving isocyanoacetate, lactamination occurred spontaneously to provide the ring-fused tetrazolo[1,5-a]pyrazin-6(5H)-one adducts 5 which after intramolecular Heck reaction gave functionalized tetracyclic tetrazolo

•  5) using seven benzaldehydes 1, two isonitriles 4, and allylamine hydrochloride (2) with trimethylsilyl azide (3) for the Ugi-azide reaction. The N-alkylations were conducted using benzyl bromide and iodomethane, respectively. The final products 8b–j were obtained in 66–74% yields. To evaluate the

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• straightforward procedure. Keywords: green chemistry; isocyanide; isonitriles; mechanochemistry; Introduction Isocyanides were first discovered more than a century ago by Lieke in Göttingen after having handled allyl iodide and potassium cyanide to synthesize crotonic acid. This attempt, instead, brought to the

• first synthetic approaches were reported by Ugi and Hofmann (Scheme 1) [3][4], who described their characteristic odour as “horrible” and “extremely distressing”. With such a breakthrough, isonitriles gained wide popularity in organic synthesis due to their extreme versatility [5][6][7]. Especially

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• ring of p-QMs 1 with functional groups such as alkyl, fluoro, bromo, trifluoromethyl, and thiophenyl was generally well tolerated (4a–g). Further, it should be noted that other activated methylene isonitriles such as methyl isocyanoacetate (2b) were also compatible with the reaction conditions

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• alkyl radicals were easily accessed by the photocatalyzed reduction of the corresponding bromides, in turn promoting an efficient radical addition onto isonitriles. In one instance, the dimeric gold complex [Au2(dppm)2]Cl2 (dppm = bis(diphenylphosphino)methane) acted as the photocatalyst and activated

• the bromoalkanes through an oxidative quenching mechanism [48]. Phenanthridines may be also formed by the initial addition of an electrophilic radical onto isonitriles. Thus, a library of 6-alkylated phenanthridines (5.2a–d in Scheme 5) and other nitrogen-based heterocycles have been prepared from

• starting from alkylhydrazines [66]. However, a heteroatom-based radical may be used for the addition onto isonitriles as well. One such example dealt with the photoredox tandem phosphonylation/cyclization of diphenylphosphine oxides with 2-arylphenylisonitriles. Here, the sequential formation of C–P and C

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• successfully undergo this cyclization (products 115f–h). C-centered radicals generated in a radical 5-exo-trig cyclization of β,γ-unsaturated oximes 116 upon oxidation by the TBAI/TBHP system were trapped by an isonitrile group of 2-arylphenyl isonitriles 117 to synthesize substituted phenanthridines 118

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction

• Yong Li,
• Zheng Huang,
• Jia Xu,
• Yong Ding,
• Dian-Yong Tang,
• Jie Lei,
• Hong-yu Li,
• Zhong-Zhu Chen and
• Zhi-Gang Xu

Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63

• removing the solvent under a gentle stream of nitrogen. Different amines, acids, and isonitriles were subjected to the one-pot protocol to give the corresponding tetramic acid derivatives 7 from the ketone intermediates 6 in good yields over two steps (51–75%) after the purification of the products by

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• a single operation [1][2][3][4][5]. Needless to say, the contribution by radical chemistry is not trivial [5][6][7]. While alkenes and alkynes have served as efficient radical donor/acceptor type C2 synthons in multicomponent radical reactions, CO and isonitriles were shown to react as donor

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• afford isothiocyanate and harmless urea [63][64][65], but one should note that the instability of the nitrile oxides leads to many byproducts, turning this approach less attractive. The synthesis of isothiocyanates starting from isonitriles involves sulfur-containing reagents such as thallium

• reaction using different isocyanides were investigated (Scheme 2). Considering the yield of various aromatic isonitriles, no significant difference was noticed between electron-withdrawing and electron-donating substituents (3c and 3d, respectively). The ortho-iodo-substituted 3b was obtained in an

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• groups of relatively high energy level with the potential of multiple reactivity are employed, for instance nitriles, isonitriles or alkynes [1][2][3][4][5][6][7][8][9]. Not surprisingly, simple or functionalized allenes have also been used in multicomponent processes and – dependent on the substitution

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

• Erika Bálint,
• Ádám Tajti,
• Anna Dzielak,
• Gerhard Hägele and
• György Keglevich

Beilstein J. Org. Chem. 2016, 12, 1493–1502, doi:10.3762/bjoc.12.146

• (Scheme 2a) [33], by the condensation of formamides and diethyl phosphite using 2,6-di-tert-butyl-4-methylpyridine (DTBMP) as the base, and trifluoromethanesulfonic anhydride (Tf2O) as the catalyst (Scheme 2b) [34], or by the reaction of isonitriles with triethyl phosphite (Scheme 2c) [35][36

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• ), in which the transition metal is omitted, relied on the trifluoromethylation of isonitriles to yield trifluoromethylphenanthridines (Scheme 7) [21]. This approach employed the Togni reagent, and Bu4NI was applied as radical initiator; whereby phenanthridines were prepared in good to excellent yields

Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• found application in MOE, and several dienophiles, such as terminal alkenes [19], isonitriles [20][21], and cyclopropenes [22][23][24], have been incorporated in carbohydrate derivatives and detected by reaction with 1,2,4,5-tetrazines [25] (Scheme 1). An important advantage of the DAinv reaction is the

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

• library of 32 different β-lactams from four β-amino acids 24, four different aldehydes and two isonitriles (Scheme 9) [41][45]. The reaction was performed in water at ambient temperature and yielded the desired products in good yields (71–89%), however, without diastereoselectivity (dr 1:1). To improve

• -approach started with an Ugi reaction of aryl aldehydes, isonitriles, D-leucine methyl ester and N-Boc-D-indanylglycine (derived from the benzhydrylimine of N-Boc-glycine, ee >99%) in methanol and afforded linear dipeptide 188 (Scheme 57). Subsequent treatment with TFA followed by base catalyzed

Post-Ugi gold-catalyzed diastereoselective domino cyclization for the synthesis of diversely substituted spiroindolines

• Amit Kumar,
• Dipak D. Vachhani,
• Sachin G. Modha,
• Sunil K. Sharma,
• Virinder S. Parmar and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2013, 9, 2097–2102, doi:10.3762/bjoc.9.246

• , Department of Chemistry, University of Delhi, Delhi-110 007, India Chemistry Building-4.20b, School of Chemistry, The University of Manchester, Manchester M13 9PL, UK 10.3762/bjoc.9.246 Abstract An Ugi four-component reaction of propargylamine with 3-formylindole and various acids and isonitriles produces

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• ammonia or an ammonia equivalent, such as 2,4-dimethoxybenzylamine (DMB-NH2), as amino component, formaldehyde as oxo-component, and a convertible isonitrile [22][23][24][25]. Although many convertible isonitriles are reported in the literature [24][26], the recently developed 4-isocyanopermethylbutane

A concise synthesis of 3-(1-alkenyl)isoindolin-1-ones and 5-(1-alkenyl)pyrrol-2-ones by the intermolecular coupling reactions of N-acyliminium ions with unactivated olefins

• Nianhong Lu,
• Lihong Wang,
• Zhanshan Li and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 192–200, doi:10.3762/bjoc.8.21

• . The coupling reactions of N-acyliminium ions with various carbon nucleophiles, such as allylsilanes, alkylmetals, TMSCN, 1,3-dicarbonyls, isonitriles, enol derivatives and aromatics has been studied extensively [15][16][17]. Few reports are found to deal with the intermolecular coupling reactions of N

A straightforward approach towards combined α-amino and α-hydroxy acids based on Passerini reactions

• Ameer F. Zahoor,
• Sarah Thies and
• Uli Kazmaier

Beilstein J. Org. Chem. 2011, 7, 1299–1303, doi:10.3762/bjoc.7.151

• isonitrile-based MCRs (IMCR) especially have developed exceptionally well during the last few decades [7][8]. Based on the pioneering work of Passerini, who observed the first three-component coupling of carbonyls with carboxylic acids and isonitriles in 1921 [9], the so-called Passerini reaction became a