Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• proceeds through a domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction sequence. Keywords: 2-aminochromene; domino reaction; imidazo[1,2-a]pyridine; 2-iminochromene; Michael addition; multicomponent reaction; oxidation; pyridine amination; Introduction Domino reactions are well

• recognized for their ability to effectively synthesize organic compounds, as far as creating two and more chemical bonds in one-step decreases waste, resources and time, and makes the development of methodology of synthesis in a domino fashion a substantial task [1]. Recently, much attention in research was

• given to domino reactions with an oxidation step, revealing possibilities for shifting the equilibrium by making products more stable or in situ generating reactive intermediates [2][3][4][5][6][7][8][9][10][11][12][13]. In its turn, multicomponent reactions (MCRs), usually occurring as domino processes

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

• -yl)-3-oxopropanenitrile; tandem reaction; Introduction The syntheses of novel heterocycles through greener protocols have received a great deal of attention of the synthetic organic chemists in view of environmental concerns [1][2][3]. The multicomponent tandem/domino reaction is one among several

• -oxopropanenitriles, aromatic aldehydes, cycloalkanones and ammonium acetate. This work also stems from our continuous effort in synthesizing novel cycloalkyl[b]pyridine-3-carbonitrile hybrid heterocycles via tandem/domino reaction [71][72]. Results and Discussion Initially the precursors viz. 3-(1H-indol-3-yl)-3

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• investigated with the objective of constructing condensed polycyclic structures. This investigation demonstrated that the generally observed domino reaction course involving a ring-opening metathesis of the norbornene unit and a ring-closing enyne metathesis is influenced to a great extent by the nature of the

• functional group and the substrate structure and may follow a different reaction course than what is usually observed. In cases where ROM–RCEYM occurred, the resulting 1,3-diene reacts in situ with the dienophile to provide condensed tetracyclic systems. Keywords: Diels–Alder reaction; domino process; enyne

• metathesis; natural products; polycarbocycles; Introduction The metathesis of norbornene derivatives having an alkene side-chain on the norbornene nucleus with Grubbs’ ruthenium catalysts has been extensively investigated. Generally the reaction proceeds through a domino process involving a ring opening of

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

• Pavel Yanev and
• Plamen Angelov

Beilstein J. Org. Chem. 2018, 14, 2602–2606, doi:10.3762/bjoc.14.238

• -protected amino acids. Domino fragmentation of the obtained intermediates leads to functionalised β-keto amides, bearing a protected amino group in their side chain. Keywords: amino acids; C-acylation; domino reaction; enamines; enaminones; keto amides; retro-Mannich; Introduction The acylation of amide

• (4) intermediates were successfully prepared, we proceeded with the removal of the Boc protection group from the ethylenediamine moiety in order to trigger the domino fragmentation to the targeted β-keto amides. In the course of these experiments the two series of compounds showed markedly different

• behaviour. Domino fragmentation of α-aminoacyl intermediates 3 to N-protected γ-amino-β-ketoamides 5 Initially we tried a procedure developed earlier by us for simpler β-keto amides (30 min in neat TFA, then aqueous NaOAc) [22]. In contrast to the preparation of non-functionalised β-keto amides, here these

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• into carbonyls [8][9][10][11][12][13][14][15][16][17], and application to cascade or domino reactions [18][19]. More recently, our group has used benzyl epoxides for the photoredox generation of carbonyl ylides which are leveraged in the synthesis of cyclic ethers [20]. This work has led us to search

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

• . Several elegant catalytic domino reactions, accordingly, have been recently designed to incorporate both aryl groups into the products. Cyclic diaryl-λ3-iodanes Cyclic diaryl-λ3-iodanes have been extensively studied for the preparation of complex polycyclic structures following the application of

• catalytic domino reactions. The group of Hayashi has reported in 2004 the first example of the transformation of a cyclic diaryl-λ3-iodane, for which both Ar–I bonds are used in a palladium cross-coupling reaction [56]. It relies on a double Heck reaction performed with methyl vinyl ketone in the presence

• domino process for the introduction of both aromatic rings of diaryl-λ3-iodanes, though a small excess of this reagent is needed to obtain good yields. An initial N-arylation reaction of 3,5-dimethylpyrazole is performed in the presence of potassium carbonate, in xylene at 70 °C, releasing 1 equivalent

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• –Hillman reactions, Friedel–Crafts reactions, aza-Henry reactions, domino reactions initiated by nucleophilic additions to isatin imines, and miscellaneous reactions. Most of the reactions depicted in this review have been promoted by a wide variety of chiral organocatalysts but chiral metal catalysts have

• isatin imine (81% yield, 86% ee with R1 = Me, R2 = H). Domino reactions In the last decade, a number of highly enantioselective domino processes [72][73][74] catalyzed by either chiral organocatalysts [26] or chiral metals have been published [75][76][77]. In 2016, Li and Li reported an efficient

• asymmetric formal [3 + 2] annulation reaction between N-Boc-isatin imines 3 and 1,4-dithiane-2,5-diol (53) as equal equivalent of 2-mercaptoacetaldehyde [78]. The domino reaction catalyzed by chiral tertiary amine-squaramide catalyst 54 began with the addition of 2-mercaptoacetaldehyde to isatin imine 3

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• only one equivalent of the iodane 1a would have been sufficient. In recent years a variety of domino C–H and/or N–H arylations as powerful tools towards selective diarylations of (hetero)arenes was employed by Greaney and co-workers, who were among the first to establish more atom-economical procedures

• organic electronics and can be obtained in good yields and an AE of 48% (Ar1 = p-Tol, Ar2 = Ar3 = Ph) using this Cu(I)-catalysed domino approach. The formation of an intermediately found diarylaniline supposedly follows a Cu(I)/Cu(III) cycle, whereas a radical mechanism is proposed for the second

• dithiocarbamates 7 and 7’ from one equivalent of diaryliodonium salt 1. Synthesis of substituted isoindolin-1-ones 9 from 2-formylbenzonitrile 8 and the postulated reaction mechanism. Domino C-/N-arylation of indoles 10. Domino modification of N-heterocycles 12 via in situ-generated directing groups. Synthesis of

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• spiro[indoline-3,2'-pyrrolidine]-2,5'-diones, via a post-Ugi-domino transamidation/cyclization sequential process, has been achieved in three sequential steps utilizing a one-pot reaction protocol. The variation in carboxylic acid substrates allows for the generation of new chiral racemic quaternary

• economical, simple and generate ample molecular diversity with the ease of using readily available starting materials. Developing new, post-modified Ugi-four-component reaction (Ugi-4CR) transformations in domino cyclization [12][13][14][15] sequences are very important for achieving unprecedented chemical

• ]. Significant efforts have been made to design creative synthetic strategies for spirocyclic oxindole molecules, of which, isatin-based domino reactions [24][25][26][27][28][29][30] have proved to be very versatile [31] and readily achievable [32][33][34][35][36][37]. However, finding a simple and efficient

An air-stable bisboron complex: a practical bidentate Lewis acid catalyst

• Longcheng Hong,
• Sebastian Ahles,
• Andreas H. Heindl,
• Gastelle Tiétcha,
• Andrey Petrov,
• Zhenpin Lu,
• Christian Logemann and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 618–625, doi:10.3762/bjoc.14.48

• LUMOs are rather high in energy [9][10][11][12]. In the past years, we demonstrated a bisboron bidentate Lewis acid (Scheme 1, A) as an efficient catalyst for the IEDDA reaction of 1,2-diazines to access 1,2-substituted aromatics [13][14]. Additionally, we could incorporate this reactivity in domino

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• halofluoroacetate. When the opposite enantiomer of the ligand (1S,2R)-59 was used under the same reaction conditions, it provided the corresponding (3R,4S) product 62a in 70% yield and 90% ee starting from the corresponding imine 60a (Scheme 23). Unfortunately, the scope of this domino Reformatsky/cyclization

• (Scheme 23). As an extension of the precedent methodology, the same ligand (1R,2S)-59 was applied to promote the enantioselective domino aza-Reformatsky/cyclization reaction of aromatic imines 60a–h with ethyl bromodifluoroacetate (26) [48]. In this case, a stoichiometric amount of this ligand was

• a stoichiometric amount of a chiral 1,2-amino alcohol ligand [45]. Reformatsky reaction of aldehydes with an enolate equivalent prepared from phenyl isocyanate and CH2(ZnI)2 performed in the presence of a chiral diarylprolinol ligand [46]. Domino aza-Reformatsky/cyclization reactions of imines with

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• shape of compound 93 makes it chiral in nature. It was proposed that there is in situ oxidation of ethanol to ethanal by conc. HNO3 which turned the reaction into a multi-component domino assembly of reactants hydrazine 14, β-ketonitriles 15 and acetaldehyde. Rahmati [75] carried out a reaction of 5

• domino reaction of 5-aminopyrazoles 16, cyclic 1,3-diones 58 and arylglyoxals 98 under microwave irradiation. Triethylamine (20 mol %) as base and DMSO as solvent at 120 °C provided best results with high yields of pyrazolo[3,4-e]indolizines (a derivative of pyrazolo[3,4-b]pyridines) 102 (Scheme 30

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• latter case, the domino-Friedel–Crafts-type cyclization proceeded via the cleavage of two carbon–fluorine bonds to afford polycyclic aromatic hydrocarbons [15][16][17][18][19][20][21]. Both types of cationic cyclization proceeded exclusively at the carbon atoms α to the fluorine substituents, because the

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• Str., 620002, Ekaterinburg, Russia Center for X-ray Diffraction Studies, St-Petersburg State University, 26 University pr., 198504, Saint-Petersburg, Russia 10.3762/bjoc.13.253 Abstract A new approach towards the synthesis of multisubstituted thiophenes is elaborated based on Rh(II)-catalyzed domino

• was also shown that α-cyanothioacetamides easily interact with dirhodium carboxylates to give rather stable 2:1 complexes, resulting in an evident decrease in the efficiency of the catalytic process at moderate temperatures (20–30 °C). Keywords: [4 + 1]-annulation; catalysis; diazo compounds; domino

• domino reactions of diazo compounds with intermediate formation of ylides [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Thus, it was for example shown that ammonium or oxonium ylides generated in the course of intermolecular processes can be easily trapped by ketones, imines, α,β-unsaturated

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• Düsseldorf, Universitätsstraße 1, D-40225 Düsseldorf, Germany 10.3762/bjoc.13.231 Abstract In situ activation of 3-arylpropiolic acids with T3P® (n-propylphosphonic acid anhydride) initiates a domino reaction furnishing 4-arylnaphtho[2,3-c]furan-1,3-diones in excellent yields. Upon employing these

• -emitting diodes (OLEDs) [2][3][4][5]. As a consequence efficient and efficacious syntheses of fluorescent molecules can be most advantageously addressed by diversity-oriented syntheses [6][7][8], namely by multicomponent [9][10][11][12][13][14][15][16][17][18][19][20][21] and domino reactions [22][23][24

• -arylnaphtho[2,3-c]furan-1,3-diones and 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones Starting from phenylpropiolic acids 1 we first set out to optimize the reaction conditions for the domino synthesis of the 4-arylnaphtho[2,3-c]furan-1,3-diones 2a and 2b with T3P® as an activating agent, varying temperature and

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

• perhydroquinoxaline derivative 73. Synthesis of ethyl 7-aminopteridin-6-carboxylates 75 via a domino reaction. Synthesis of morhpolin-2-ones 80 from E-1 and β-aminoalcohols 78 through an initial aza-Michael addition and subsequent heterocyclization step. Reaction of 3-amino-5-arylpyrazoles 81 with dialkyl

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• reagents; (3) the elaboration of tandem and domino-processes utilizing conjugate addition of C-nucleophiles to nitrosoalkenes and finally, (4) the design of catalytic enantioselective versions of the Michael addition to nitrosoalkenes (for advances in catalytic asymmetric cycloadditions of nitrosoalkenes

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