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

• chromones via domino chromone ring construction and C(sp2)–H bond sulfenylation have been achieved under transition-metal-free conditions by using KIO3 as the only catalyst. Keywords: C–H sulfenylation; chromones; domino reaction; free-radical; transition-metal-free; Introduction The C–S bond-forming

• as KI, I2 or KIO3 could all catalyze the domino reaction to provide product 3a, wherein KIO3 displayed the highest catalytic activity (entries 2–4, Table 1). On the other hand, in the reactions performed in different media, including DMSO, ethyl lactate (EL), EtOH, MeCN, 1,4-dioxane and toluene, DMF

• (reaction 1, Scheme 3). In addition, sulfonyl hydrazine 2b gave disulfide 6 under the same conditions (reaction 2, Scheme 3), suggesting that chromone 5 and disulfide 6 might be key intermediates in the domino reactions. Moreover, the same reaction in the presence of TEMPO gave no formation of 6, indicating

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

• also in domino [14] and asymmetric catalytic processes [15]. Due to its versatility, the Mizoroki–Heck reaction is extensively employed in the synthesis of pharmaceutical, agrochemical and natural products, and continues to attract attention within the synthetic chemists’ community [16][17][18]. From

N-Propargylamines: versatile building blocks in the construction of thiazole cores

• S. Arshadi,
• E. Vessally,
• L. Edjlali,
• R. Hosseinzadeh-Khanmiri and
• E. Ghorbani-Kalhor

Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61

• domino reactions of N-propargylamines 20 with isothiocyanates 21 developed by Castagnolo. Electrophile-mediated cyclization of N-propargylthioureas 55.

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

• 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

Symmetry-based approach to oligostilbenoids: Rapid entry to viniferifuran, shoreaphenol, malibatol A, and diptoindonesin G

• Youngeun Jung,
• Dileep Kumar Singh and
• Ikyon Kim

Beilstein J. Org. Chem. 2016, 12, 2689–2693, doi:10.3762/bjoc.12.266

• diptoindonesin G, a potent cytotoxic and immunosuppressant agent [16][17], by using a highly efficient domino cyclodehydration/intramolecular Friedel–Crafts acylation/regioselective demethylation sequence as a key transformation. Very recently, a dual functional role of diptoindonesin G in modulating α and β

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

• Olga C. Dennehy,
• Valérie M. Y. Cacheux,
• Benjamin J. Deadman,
• Denis Lynch,
• Stuart G. Collins,
• Humphrey A. Moynihan and
• Anita R. Maguire

Beilstein J. Org. Chem. 2016, 12, 2511–2522, doi:10.3762/bjoc.12.246

• ready access to appreciable quantities of material is required. Preparation of α-thio-β-chloroacrylamides typically results from a three-step synthetic route, culminating in a final cascade/domino reaction [13] where a toluene solution of α-thioamide and NCS is subjected to a ‘hot plunge’ by placing it

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• a RY dimer [9]. The substrate is ionised by diphosphate abstraction and the resulting allyl cation undergoes a domino reaction via a series of cationic intermediates and a final deprotonation or attack of water to yield a terpene hydrocarbon or alcohol. This reaction cascade proceeds in a

Rapid regio- and multi-coupling reactivity of 2,3-dibromobenzofurans with atom-economic triarylbismuths under palladium catalysis

• Maddali L. N. Rao,
• Jalindar B. Talode and
• Venneti N. Murty

Beilstein J. Org. Chem. 2016, 12, 2065–2076, doi:10.3762/bjoc.12.195

• the synthesis of 2,3-dialkenylbenzofurans and functionalized dibenzofurans with domino “twofold Heck/6π-electrocyclization” of 2,3-di- and 2,3,5-tribromobenzofuran substrates [34]. In this regard, the cross-coupling studies of triarylbismuth reagents in regioselective studies with functionalized

Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II)-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

• Valerij A. Nikolaev,
• Jury J. Medvedev,
• Olesia S. Galkina,
• Ksenia V. Azarova and
• Christoph Schneider

Beilstein J. Org. Chem. 2016, 12, 1904–1910, doi:10.3762/bjoc.12.180

• provides a good way for the synthesis of multi-functionalized N-arylpyrrolidines by the same “metal–carbene” methodology with yields of up to 82% [15]. The reactions occur as a domino process involving an initial formation of N-ylides A followed by the intramolecular Michael addition with the conjugated

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• double bond in readily available 3-arylmethylene-2,5-piperazinediones, followed by a domino process involving three consecutive nucleophilic attacks that achieve regioselective opening of the diketopiperazine ring and diastereoselective generation of the aziridine ring. The protocol described here

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

• Bo Yang,
• Chuanye Tao,
• Taofeng Shao,
• Jianxian Gong and
• Chao Che

Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145

• of the GBB reaction involving ketones, transforming the simple starting materials into complex heterocycles of pharmaceutical relevance in a highly efficient fashion. The developed MCR proceeds through a domino GBB/retro-aza–ene/nucleophilic cyclization process under mild reaction conditions, and its

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• , carbamate 138, hexahydrobenzothiophene 140 and benzothiophene 142 were converted to the corresponding bisphosphonates 139, 141 and 143, respectively (Scheme 30). The synthesized heterocyclic bisphosphonates showed anti-inflammatory properties. 3 Knoevenagel-induced domino reactions An efficient method into

• phosphorylated heterocycles is the condensation of an activated methylene component with a carbonyl compound followed by subsequent transformations such as intramolecular cyclization, Michael-type addition and hetero-Diels–Alder cycloaddition. 3.1 Domino Knoevenagel/phospha-Michael process A convenient one-pot

• conditions are summarized in Table 1. 3.2 Domino Knoevenagel/hetero-Diels–Alder process The one-pot synthesis of dihydropyrans via a three-component reaction between an activated methylene compound, an aldehyde and an electron-rich alkene was firstly reported by Tietze et al. [72]. Collignon et al. applied

Synthesis of β-arylated alkylamides via Pd-catalyzed one-pot installation of a directing group and C(sp³)–H arylation

• Yunyun Liu,
• Yi Zhang,
• Xiaoji Cao and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2016, 12, 1122–1126, doi:10.3762/bjoc.12.108

• context, developing alternative strategies which are able to skip the DG-installing procedure is of high emergence in the chemistry of DG-based C–H activation. To solve the problem of additional cost resulted from the DG installation, the concept of domino reaction in which the multiple chemical bond

• known syntheses, a domino process by which the AQ can be linked directly to the raw substrates to enable the subsequent arylation transformation in one pot would be highly favorable for enhancing step economy. Upon this assumption as well as our interest in both domino reactions and C–H

• ]. Herein, we report our results in the establishment of a complementary one-pot domino approach without prior DG installation for the synthesis of diverse arylated alkylamides. Results and Discussion To start the exploration, the reaction of AQ 1, butyryl chloride (2a) and iodobenzene (3a) was selected as

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

• ; domino aldol; metal enolate; tetrahydropyran; Introduction Since its discovery in the late nineteenth century the aldol reaction has become one of the most powerful tools in the field of carbon–carbon bond formation [1][2][3][4][5]. It is widely used in the formation of many natural products [6][7][8][9

• the years [31]. We have already reported a domino aldol–aldol–hemiacetal process that furnishes racemic tetrahydro-2H-pyran-2,4-diols in a highly stereoselective manner (Scheme 1) [30][31][32][33][34][35][36][37]. In this paper, the domino aldol–aldol–hemiacetal reaction involving several metals (Al

• , Ga, In, Ti, Zr, Sn), and various aldehydes and ketones is studied experimentally and computationally. Results Metal effect The experiments were performed to screen suitable metal fragments for their ability to promote the domino aldol reaction by studying the reaction between propiophenone (1a) and

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• studies [123][124]. It should also be noted that a biomimetic domino guanidinylation–aza-Michael-addition reaction for the synthesis of the capreomycidine scaffold has been developed, which only furnished the target structures as stereoisomeric mixtures though [125]. The epicapreomycidine-derived

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• through an organocatalyzed asymmetric domino-Michael addition/Henry reaction (Scheme 8) [36]. These heterocyclic products are important chiral building blocks for the synthesis of organocatalytic frameworks and ligands for chiral metal complexes, both with the potential ability to induce chirality. They

• -nitrovinyl)benzaldehyde derivatives 20 to give the highly functionalized cis-1-hydroxy-2-nitroindane-based indole compounds 21 with excellent yield, high selectivity and good diastereomeric ratios (dr) (Scheme 8). In the reaction pathway proposed to explain this domino reaction, both substrates are activated

• substituted product 14. Reaction pathway proposed for the preparation of the compounds 14. The enantioselective synthesis of cis-vicinal-substituted indane scaffolds 21, catalyzed by ent-6. Asymmetric domino procedure (Michael addition/Henry cyclization), catalyzed by the thioamide ent-6 which involves a cis

(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

• enantioselective domino-Michael–Henry reaction catalyzed by a secondary amine-thiourea between cyclohexa-1,4-dienone (44) and a γ,δ-alkyl-aryl-disubstituted nitrodiene 45, providing bicyclo[3.2.1]octan-2-one 46 (Scheme 16) [26]. The organocatalyst used in this reaction is the cyclic thiourea 47. It is noted, that

• 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

• . 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

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• then turn to asymmetric 1,2-additions followed by conjugate additions, a cyclopropanation, (ep)oxidations, α-functionalisation processes, cycloadditions, domino processes and finally miscellaneous reactions. We ultimately aim to demonstrate through this plethora of diverse processes, that the 6’-OH

• give the corresponding thietanes 96. In another example of how a different catalyst can lead to a different product, the authors demonstrated that the use of DABCO led instead to the [4 + 2] adduct (Scheme 22) [66]. Domino reaction Although it could be argued that some of the reactions within this

• review are already domino reactions (e.g., MBH, and the cyclopropanation), a recent and clearer example of the use of a 6’-OH cinchona derived catalyst in such a process comes from the laboratory of Samanta and co-workers [67][68]. They have demonstrated an enantioselective domino reaction between 3

A quadruple cascade protocol for the one-pot synthesis of fully-substituted hexahydroisoindolinones from simple substrates

• Hong-Bo Zhang,
• Yong-Chun Luo,
• Xiu-Qin Hu,
• Yong-Min Liang and
• Peng-Fei Xu

Beilstein J. Org. Chem. 2016, 12, 253–259, doi:10.3762/bjoc.12.27

• . Previously, we established organocatalytic domino reactions to construct very useful molecular architectures [47][48][49][50][51][52][53][54][55][56][57][58][59][60]. Based on this past experience, we decided to develop a one-pot quadruple protocol to construct this difficult molecular architecture using

Recent applications of ring-rearrangement metathesis in organic synthesis

• Sambasivarao Kotha,
• Milind Meshram,
• Priti Khedkar,
• Shaibal Banerjee and
• Deepak Deodhar

Beilstein J. Org. Chem. 2015, 11, 1833–1864, doi:10.3762/bjoc.11.199

• syntheses of virgidivarine and virgiboidine by employing an intramolecular ene–ene–yne domino RRM protocol in combination with an oxidative C–C bond cleavage. This protocol opens-up new opportunities for the construction of intricate dipiperidine-based targets in a stereoselective manner (Scheme 12). Lee

• compound 269 was obtained from oxabicyclo adduct 268 by a domino metathesis sequence in the presence of catalyst 2. Moreover, compound 269 was obtained as a single diastereomer and constitutes the core structure of phelligridin G (Scheme 55). In 2009, Hanson’s group reported [56] the synthesis of

• skeletally diverse bi-, and tricyclic sultam derivatives (sulfonamide analogs) using norbornenyl sultam 272 as a core unit assembled by an intramolecular Diels–Alder (IMDA) reaction via a domino ROM–RCM–CM cascade. Diversity has been incorporated by using various cross-metathesis partners (Scheme 56). Basso

Fe(II)/Et₃N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives

• Ekaterina E. Galenko,
• Olesya A. Tomashenko,
• Alexander F. Khlebnikov,
• Mikhail S. Novikov and
• Taras L. Panikorovskii

Beilstein J. Org. Chem. 2015, 11, 1732–1740, doi:10.3762/bjoc.11.189

• alkyl 2H-azirine-2-carboxylates can be prepared by isomerization of 5-alkoxyisoxazoles under Fe(II)-salt catalysis [30]. Quite recently this isomerization has been used for the preparation of substituted pyrrole-2-carboxylic acid derivatives by the domino reaction of 3-aryl-5-methoxyisoxazoles with 1,3

• by Et3N; 3: activation of azirine 8 with Et3HN+Br−; 4: reaction of the activated azirine 11 with the imidazolium ylide 10) as a domino reaction under relay catalysis [35][36]. A simple procedure, consisting of stirring a mixture of isoxazole 7, phenacylimidazolium salt 9, FeCl2·4H2O and Et3N in MeCN

• domino sequence leading to 5-alkoxycarbonylpyrrol-3-ylimidazolium salts 1. The synthesis of methyl 4-(1H-imidazol-1-yl)-1H-pyrrole-2-carboxylates 12. The hydrolysis of ylide 2a and bromide 1b. The synthesis of 5-alkoxycarbonylpyrrol-3-ylimidazolium salts 1 by the domino reaction of 5-methoxyisoxazoles 7

An efficient synthesis of N-substituted 3-nitrothiophen-2-amines

• Sundaravel Vivek Kumar,
• Shanmugam Muthusubramanian,
• J. Carlos Menéndez and
• Subbu Perumal

Beilstein J. Org. Chem. 2015, 11, 1707–1712, doi:10.3762/bjoc.11.185

• goals of green chemistry [32]. In this context, we wish to report herein a new and efficient synthesis of 3-nitro-N-aryl/alkylthiophen-2-amines based on domino reactions between α-nitroketene N,S-aryl/alkylaminoacetals and 1,4-dithiane-2,5-diol, the dimer of 2-mercaptoacetaldehyde (Scheme 2). This work

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• convenient eight-step sequence from kaempferol to 3 through regioselective methylation and a domino Claisen–Cope rearrangement that delivered 3 in 26% overall yield. The NMR spectra of synthetic 3 (see Supporting Information File 1 for experimental and spectral data) were in accordance with the reported ones

Hydrogenation of unactivated enamines to tertiary amines: rhodium complexes of fluorinated phosphines give marked improvements in catalytic activity

• Sergey Tin,
• Tamara Fanjul and
• Matthew L. Clarke

Beilstein J. Org. Chem. 2015, 11, 622–627, doi:10.3762/bjoc.11.70

• to be addressed with new catalysts. In a recent study on hydroaminomethylation, i.e., domino hydroformylation–enamine formation–enamine hydrogenation, we noted that the enamine hydrogenation was the slowest reaction in the process, and use of an electron-deficient phosphine sped up the reduction step

Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• formation of quaternary β-amino-ethers and -alcohols. The new reaction conditions guarantee good selectivity by preventing the formation of secondary products. The secondary products are possibly derived from a competitive domino reaction, which involves further oxidation of the ketyl radicals. Keywords

• transformation significantly affected the selectivity in the desired products. Taking advantage of this secondary process, we performed a domino reaction, where the alcohol served as the source of both the nucleophilic radical and the aldehyde necessary for the in situ formation of the aldimine (Scheme 2, entry

• a) [29]. Surprisingly, the same reaction was even more efficient when performed in the presence of the Ti(IV)/Zn/t-BuOOH system (Scheme 2, entry b). Under the latter conditions, the domino approach was also successfully extended to cyclic ethers, promoting the consecutive electrophilic amination to