Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• ; multi-step reactions; multicomponent reactions; one-pot synthesis; organocatalysis; tandem reactions; transition-metal-catalysis; The synthesis of pharmaceutical ingredients, natural products, agrochemicals, ligand systems, and building blocks for materials science has reached a high level of

• stereocenters [7]. In the Review paper by Kisszékelyi and Šebesta, the diverse variety of chiral metal enolates obtained by asymmetric conjugate additions of organometallic reagents and the possibilities to engage metal enolates in tandem reactions with new electrophiles are presented [8]. A Perspective from X

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• –Crafts reactions, rather than an oxocarbenium. Keywords: 1-aryltetralines; Friedel–Crafts reaction; Hock rearrangement; oxidative cleavage; tandem reactions; Introduction The Hock cleavage [1] consists in the acid-catalyzed rearrangement of organic hydroperoxides, leading to the oxidative cleavage of a

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• levels of chiral induction, paving the way to enantioenriched β2-amino acids and β2,2-amino acids. Keywords: β-amino acids; tandem reactions; radical–polar crossover; tert-butanesulfinamide; zinc radical transfer; Introduction Dialkylzinc reagents react in aerobic medium with a range of α,β-unsaturated

• benefit from a similar effect, even though in this case, the direct formation of an intermediate enolate remains uncertain [11]. With this context in mind, we surmised that β-aminoenoates I could be suitable 1,4-acceptors (Scheme 2, bottom). We previously reported tandem reactions of such substrates

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• , crop-protecting agents, or advanced materials. Their syntheses often involve numerous reaction steps requiring laborious isolation and intermediate product purification steps. An important strategy for improving syntheses’ effectiveness is the concept of domino reactions, cascade, or tandem reactions

• nucleophile (R3Zn−) to the ketone with moderate yields but still good stereoselectivities (Scheme 9B). In 2018, Wang and co-workers extended the group of applicable electrophiles for the zinc enolate-based tandem reactions. Following the conjugate addition of Et2Zn to acyclic α,β-unsaturated ketones 41, they

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

• important C1 synthon. Its special reactivity, such as the ability to react with electrophilic, nucleophilic, and radical reagents [25][26][27][28], determines that it can participate in many types of reactions such as multicomponent reactions [29][30][31][32], tandem reactions [33][34], and insertion

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• , tandem reactions, and the total synthesis and biosynthesis of natural products. This review explores the use of α-ketol rearrangements in these contexts over the past two decades. Keywords: acyloin rearrangement; asymmetric synthesis; iminol rearrangement; ketol rearrangement; tandem reactions

• base or Lewis acid, the possibility exists to couple the rearrangement to other compatible reactions without any intervention. Such tandem reactions are attractive synthetic “tricks” that can allow for complex modifications with efficiency and often high selectivity. This short section introduces this

• concept by application to isolated reactions, while in the following section, examples of tandem reactions in total syntheses are given. Inspired by the direct ring expansion of 1-alkynylcyclobutanols to α-methylenecyclopentanones catalyzed by gold reported by Toste and co-workers [9], Kim et al

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

• condensation of α-halogenated carbonyl compounds, β-dicarbonyl compounds and amines; and iv) the latest developed multicomponent tandem reactions and transition metal-catalyzed coupling reactions [30][31][32][33][34][35][36][37][38][39]. Recently, substantial achievements have been made using azides as a

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• ; electron transfer; γ-lactams; tandem reactions; Introduction Nitrogen-containing heterocycles are widely distributed in biologically active compounds [1][2][3][4]. Saturated nitrogen heterocycles such as pyrrolidines [5][6][7][8][9], piperidines, pyrrolizidines or indolizidines [10][11][12][13][14][15][16

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• selenium source in the presence of a transition metal catalyst, such as Cu or Ni [27][28][29][30][31][32]. In 2011, Zhou et al. reported the pioneering Cu-catalyzed C–H selenation of 2-arylimidazopyridine with diphenyl diselenide in the presence of CuI (10 mol %) [29]. Tandem reactions involving the

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• to build the desired 1,3-dienic units. The advantageous association of this approach with name reactions like Grignard, Wittig, Diels–Alder, Suzuki–Miyaura, Heck cross-coupling, etc. is illustrated. Examples unveil the generality of such tandem reactions in providing not only the intricate structures

• of known, in vivo effective substances but also for designing chemically modified analogs as valid alternatives for further therapeutic agents. Keywords: bioactive compounds; enyne metathesis; ring-closing metathesis; ruthenium catalysts; tandem reactions; Introduction Alkene and alkyne metathesis

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• reaction of compound 4 if it did not possess an alkyl substituent on the nitrogen atom of the amide bond. Conclusion In summary, we have developed two types of tandem reactions catalyzed by a copper salt. The reaction of 2-bromocarbonyl compounds and aryl-substituted alkynes underwent alkyl radical

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• transformation [14][15][16][17][18][19][20][21][22]. Hence, multicomponent tandem reactions minimize the number of steps to synthesize complex heterocycles, avoid the isolation and purification of the intermediates, allow less waste to the environment, shorten the reaction time and are also cost effective

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• transformations involving stoichiometric amounts of λ3- or λ5-iodanes, thus, has been improved by designing tandem reactions that allows for incorporating the aryl motif into the products through a subsequent one-pot nucleophilic addition or catalytic coupling reaction. This review summarizes the main

• achievements reported in this area. Keywords: atom-economy; couplings; hypervalent iodine; oxidation; tandem reactions; Introduction Synthetic applications of the hypervalent iodine chemistry have grown exponentially in the last four decades as highlighted by several books and comprehensive reviews dedicated

• transformations always lead to the release of 2-iodobenzoic acid in the reaction mixture. Thus, with the aim to value this side product, a variety of tandem reactions including an oxidation and an addition step have been designed to incorporate the nucleophilic acid into the final product. λ5-Iodane reagents One

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• of catalysts in a nanoreactor facilitates one-pot tandem reactions that, in most cases, require two or more incompatible catalysts [22][57]. Catalyst confinement leads to a high local concentration of the substrate at the active site, which results in higher reaction rates and better conversion [9

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

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• products (tandem reactions). These reactions occur through an initial formation of the Michael-type adduct followed by a heterocyclization step upon involvement of either a cyano or an ester group as a second electrophilic center. Hydrazine is a powerful dinucleophile and reacts easily with E-1 in ethanol

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO₃-catalyzed radical C(sp²)–H sulfenylation

• Yanhui Guo,
• Shanshan Zhong,
• Li Wei and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2017, 13, 2017–2022, doi:10.3762/bjoc.13.199

• efforts in exploring enaminone C(sp2)–H bond sulfenylation [40][41] reactions have led us to establish the synthesis of 3-sulfenylated chromones via KIO3-catalyzed tandem reactions of o-hydroxylphenylenaminone and thiophenols via tandem C–H sulfenylation and intramolecular C–N bond oxygenation (B, Scheme

• protocol toward these compounds through the tandem reactions between o-hydroxyphenylenaminones and sulfonyl hydrazines. In this method, the construction of the target products is furnished via the key C–H sulfenylation without using any transition metal catalyst or oxidative additive. Results and

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• other hand, and in order to further explore the scope of the PVP-Pd NPs catalyst, the synthesis of stilbene derivatives by Pd-tandem reactions was carried out. Some synthetic methods employing consecutive Pd Hiyama–Heck coupling reactions have been reported to obtain a variety of stilbene derivatives

Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions

• Andreas C. Boukis,
• Baptiste Monney and
• Michael A. R. Meier

Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7

• ; multicomponent reactions; Passerini reaction; tandem reactions; Introduction Multicomponent reactions (MCRs) are fascinating straightforward reactions for the preparation of diversely substituted products starting from three or more precursor molecules, forming products containing atoms/moieties of all

• the Passerini α-acyloxycarboxamide adduct 12 [18]. Tandem reactions Tandem reactions (also known as cascade [22] or domino reactions [23]) are chemical transformations that involve at least two independent reactions utilizing different functional groups with distinct chemical reactivities [24][25][26

• ][27]. So far, only a few examples of multicomponent tandem reactions are described in the literature [28][29]. Portlock et al. reported on Petasis–Ugi tandem reactions leading to a product with six different side chains [30][31]. Al-Tel et al. combined the Groebke–Blackburn reaction with either

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• novel tandem reactions for the synthesis of complex natural products [29][32][33][34][35][36][37], we have developed an innovative concept for heterocycles synthesis [26][27][28][29][30][31]. As shown in Scheme 1, this approach that further advances and generalizes several individual reports by other

Scope and mechanism of the highly stereoselective metal-mediated domino aldol reactions of enolates with aldehydes

• M. Emin Cinar,
• Bernward Engelen,
• Martin Panthöfer,
• Hans-Jörg Deiseroth,
• Jens Schlirf and
• Michael Schmittel

Beilstein J. Org. Chem. 2016, 12, 813–824, doi:10.3762/bjoc.12.80

• ][10][11], stereoselective syntheses [12][13][14][15][16], and tandem reactions [17][18][19]. While the latter processes usually comprise only one aldol reaction, tandem reaction sequences containing two consecutive aldol steps are mostly limited to the trimerization of enolates [20][21][22]. Metal

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• nitronate, which reacts with the electrophilic nitroolefin via a Michael addition. The resulting nitro compound is again deprotonated by the organocatalyst and reacts with the α,β-unsaturated ester to yield the desired product. Cascade/domino/tandem reactions producing six-membered rings Cascade and tandem

• reactions always seemed very appealing to the synthetic community, not only because of their elegance, but also for their efficiency [36][37][38][39][40][41][42]. Cascade and tandem reactions have been proven extremely efficient because in only one synthetic operation, many bond-forming steps are achieved

• . Organocatalysis has made many contributions in cascade and tandem processes [43][44][45], due to the mild conditions required for the organocatalysts to operate, many distinct reactions can be conducted in one-pot fashion. Cascade/domino/tandem reactions producing six-membered rings initiated by Michael addition

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• preliminary study on sonochemical Staudinger-aza-Wittig tandem reactions [20] proving that isocyanate and urea formation is strongly favored. However, the applied power must be optimised for the best conversions of azido-CD into urea to be obtained and if lower efficiency in the second step is to be avoided

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones

• Srinivas Thadkapally,
• Athira C. Kunjachan and
• Rajeev S. Menon

Beilstein J. Org. Chem. 2016, 12, 16–21, doi:10.3762/bjoc.12.3

• ], multicomponent reactions [8], ring-closing metathesis approaches [9][10], tandem reactions of 1,3-dicarbonyl compounds [11][12] and cyclocondenzation reactions of salicylic aldehydes with α,β-unsaturated carbonyl compounds [13][14][15]. The utility of some of these methods are limited by drawbacks such as

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• cross metathesis of 1 with methyl acrylate was transformed by means of nucleophilic ring-opening of the epoxide to furnish a diol, an alkoxy alcohol and an amino alcohol in high yields. Keywords: cross metathesis; epoxide; ruthenium catalysts; tandem reactions; Introduction Catalytic carbon–carbon