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

• assistance and support. Svetlana B. Tsogoeva Erlangen, January 2024 Comparison of a classical “stop-and-go” synthesis with a domino reaction.

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• -mediated domino reaction of chromone-3-carboxaldehydes and amines [41], Pd-catalyzed redox-neutral C–N coupling reaction of iminoquinones with electron-deficient alkenes [42], NH3 insertion into o‑haloarylynones [43], gold(III)-catalyzed azide-yne cyclization [44], Michael/Truce-Smiles rearrangement

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• nitrostyrenes with previously prepared oxindole-functionalized dihydrobenzofuranones (reaction 2 in Scheme 1) [52]. We reported a piperidine-promoted domino reaction of thiophenols and two molecules of 3-phenacylideneoxindoles to give multifunctionalized dispirocyclopentanebisoxindoles (reaction 3 in Scheme 1

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• domino reaction of enamines with azlactones [22][23][24][25][26][27][28][29][30]. We have previously reported a plausible mechanism of such reactions [22][25]. 1H-Pyrazol-5-amines also enter into similar transformations with azlactones in various solvents. The yields of tetrahydro-1H-pyrazolo[3,4-b

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• ) [65]. In 2019, Piersanti and co-workers reported an organocatalyzed enantioselective aza-Friedel–Crafts/lactonization domino reaction sequence as the key step in the course of synthesizing (+)- and (−)-fumimycin. (−)-Fumimycin was first isolated from Aspergillus fumisynnematus and exhibits

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• explain why at lower onium salt amount and shorter reaction times the diastereoselectivities are higher but at the expense of the overall yield. With the optimized reaction conditions in our hands, we next explored the scope of the domino reaction. Structurally diverse onium compounds 2 were tested to

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

• , we have investigated the domino reaction of the formed metal enolates with activated alkenes 91 [59]. Alkenes with two activating groups were needed for efficient enolate-trapping reactions, sulfone or phosphonate activating groups being the most suitable ones (Scheme 23). Harutyunyan and co-workers

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• branch of organic chemistry dedicated to the synthesis of highly functionalized products through sequential transformations in a single reaction. Classically, a domino reaction has been defined by Tietze as a reaction involving two or more bond-forming transformations that take place under the same

• suppress β-heteroatom elimination enabling sequential electrophilic trapping of the alkylzinc complex. Although this reaction would more closely fall under the definition of a telescoped reaction than a strict domino reaction, this methodology allowed for the synthesis of difunctionalized strained alkenes

• -catalyzed [3 + 2] annulation/ring-opening/dehydration domino reaction of oxabicyclic alkenes 30 with 2-(1-methylhydrazinyl)pyridine (MHP) directed arenes 87 for the synthesis of benzo[b]fluorenones 88 (Scheme 16) [52]. C–H bond functionalization with heterobicyclic alkenes as annulation partners has

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• concept proved to be difficult to achieve, but by optimization of different parameters of this Domino reaction, the required enantiomerically almost pure ketones 9–11 were obtained (Table 1). The Mannich reaction worked best using diisopropylammonium trifluoroacetate as the catalyst [22]. The isolation of

• ), diisopropylamine (0.4 equiv), TFA (0.1 equiv), THF, reflux, 3 d, ii) maleic anhydride (1.2 equiv), reflux, 16 h; d) MeMgBr (3.0 equiv), THF, reflux, 4 h. Screening of different reaction conditions with the (S)-Jørgensen’s organocatalyst S-16 for the key Domino reaction, consecutive Mannich and intramolecular Diels

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• at room temperature resulted in 3,3-dicyano-5-hydroxy-5-arylcyclopent-1-ene-1,2-dicarboxylates in high yields. More importantly, the DABCO-promoted domino reaction of two molecules of each phenacylmalononitrile and dialkyl but-2-ynedioate in acetonitrile at room temperature afforded unique

• final product 4. It is due to the in situ formation and ring-opening of 2-oxabicyclo[2.2.1]hept-5-ene, that only one diastereoisomer 4 with the aryl group and the remaining cyano group in cis-position was selectively formed in the domino reaction process. In order to shed light on the proposed reaction

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• isatylidene malononitriles or 3-(ethoxycarbonylmethylene)oxindoles for the efficient construction of two kinds of spiro[cyclohexane-1,3'-indolines] in good yields and with good diastereoselectivity. Additionally, tri(n-butyl)phosphine promoted the domino reaction of isatins and ethyl isatylidene cyanoacetates

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• several research groups. In 2013, Yan et al. reported the construction of dispirocyclopentanebisoxindoles from the base-catalyzed domino reaction between two molecules of 3-phenacylideneoxindoles by participation of different solvents [23]. In 2016, the same research group reported the synthesis of

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• backbone. Expected 9-aminofluorene intermediates 5 were envisaged to undergo subsequent oxidation by the same oxidant to hopefully provide the fluorenones 3 in a domino reaction. Results and Discussion After comprehensive literature search for successful oxidations of benzylic C–N bonds we tested a variety

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• with benzylideneacetone gave the desired carbazoles 6m and 6n albeit in significantly lower yields. Thus, this one-pot domino reaction successfully constructed carbazoles with four substituents on the benzene ring from the corresponding indole derivatives with two molecules of chalcones. It should be

• structure of the isomer 4g. Synthesis of tetrahydropyrrolo[3,4-c]carbazoles 3a and 3b. Proposed domino reaction mechanism for the formation of carbazoles 6. Synthesis of pyrrolo[3,4-c]carbazoles 4a–l.a Synthesis of the polysubstituted carbazoles 6a–n.a Supporting Information Supporting Information File 344

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• alcohols with diaryliodonium salts [26], the Sc(OTf)3-catalyzed domino reaction [27], and the iodine-catalyzed nucleophilic substitution reaction of xanthen-9-ol [28]. As an example of an intramolecular hydroarylation of an olefin, 9,10-dihydroacridines, which are N derivatives of xanthenes, were

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• with high ee in the two first cycles, although the yield of the product in the first cycle was lower (Scheme 28b). Finally, the absolute configuration of the products was determined by ECD analysis. Zheng et al. described an asymmetric organocatalyzed domino reaction between 4-hydroxycoumarins 1 and

• this catalyst in a domino reaction of pyranocoumarins 99 [67]. The procedure proved to be efficient for obtaining products with good to excellent yields and enantiomeric excesses, and in some cases starting from three components in a one-pot procedure (Scheme 32). The chiral catalyst 100 allows the

• reaction between 3-cyano-4-methylcoumarins 39 and MBH carbonates 40. Enantioselective synthesis of cyclopropa[c]coumarins 45. NHC-catalyzed lactonization of 2-bromoenals 46 with 4-hydroxycoumarin (1). NHC-catalyzed enantioselective synthesis of dihydrocoumarins 51. Domino reaction of enals 2 with

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• alkaloid ingenine B [20]. The iodine-catalyzed [3 + 3] cycloaddition of indolyl alcohol to enaminones [21] and the thiourea-catalyzed iso-Pictet–Spengler reaction of isotryptamine with aldehydes [22], are some noteworthy contributions to the field. A cascade or domino reaction is an interesting approach

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• , various metal-based approaches for arylation of quinone involving electrochemical [32], oxidative [33], and photochemical methods [34][35][36] are also available in the literature [37]. Langer and co-workers reported the synthesis of benzofuropyridines based on a domino reaction of 3-chlorochromones with

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• exploring the MC-MWA reactions Jiang and co-workers [41] designed a microwave facilitated regioselective four-component domino reaction employing naphthyl- or anthracenylamine 10, aldehydes 5 and 2-hydroxy-1,4-naphthoquinone (11) in acetic acid for the construction of dibenzo[a,h]acridine-12,13(7H,14H

• first time reported a microwave-assisted four-component domino reaction involving acyclic 1,3-diketones 54, amines 32, diethyl malonate (126) and triethyl orthoformate (111) for the synthesis of substituted pyridone derivatives 127 at 120 °C under catalyst- and solvent-free conditions. The reaction

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• carbonyl compounds for the synthesis of heterocyclic compounds has been repeatedly demonstrated [2][3]. We recently used a domino reaction of amino acid, ketone and dimethyl fumarate for the one-pot synthesis of a substituted pyrrolidine, which then was converted into a reduction-resistant pyrrolidine

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

• domino reaction of aldehydes 1, 2-aminopyridines (2-APs) 3 and terminal alkynes 2, catalyzed by CuI and co-catalyzed by the NaHSO4·SiO2 system (Scheme 1). The reaction performed with CuI alone gave a moderate yield of the product (only 45%) whereas NaHSO4·SiO2 alone was unable to complete the reaction

• catalytic activity exhibited by Cu(0) NPs Chenglong et al. have reported an efficient, three-component one-pot reaction for the synthesis of imidazo[1,2-a]pyridines [111]. The protocol enjoyed a solvent-free domino reaction between compounds 3, 1 and 2 under nitrogen atmosphere at 120 °C (Scheme 15

Efficiency Eff_syn of complex syntheses as multicomponent reactions, its algorithm and calculations based on concrete criteria

• Heiner Eckert

Beilstein J. Org. Chem. 2019, 15, 1425–1433, doi:10.3762/bjoc.15.142

• components for linking, and also generates its own structure which is capable of extensions like the domino reaction types [5]. An Ugi reaction is used in the total synthesis of the extremely potent antitumor agent ecteinascidin-743 (Et-743, 1) by Fukuyama to form a large part of the skeleton 2 (Scheme 5

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• base led to a fused chromanyl-cyanopyridine. High selectivity, high atom economy, and good to high yields in addition to mild reaction conditions are the advantages of this approach. Keywords: chromane; domino reaction; fused heterocyclic skeletons; pyrazolopyridines; Introduction The synthesis of

• construct fused heterocyclic skeletons [37][38][39][40], we describe the synthesis of pyrazolopyridines 4a–m containing a chromone moiety (Scheme 1). The synthetic approach was based on a domino reaction of (arylhydrazono)methyl-4H-chromen-4-one 1a–g, primary amines 2a–c, and malononitrile (3) in the

• fused heterocyclic backbones with high selectivity. Conclusion In conclusion, we have successfully established an efficient route toward the synthesis of a diverse array of fused heterocyclic skeletons through a domino reaction. We showed an interesting behavior of the base for the cyclization reaction

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• alkynylation for the aryl iodides. In this paper, we developed an efficient domino reaction of aryl iodides with ortho-bromobenzoyl chlorides and norbornadiene leading to phenanthrene derivatives, which could be widely used in the synthesis of vital intermediates for functional materials, pharmaceutical agents

• compound z-6 was isolated in 88% yield. Based on the above experimental results and the use of norbornadiene in Catellani reactions followed by retro-Diels–Alder reaction firstly reported by Lautens et al. [22][23][24], which is mentioned in recent works [11], a proposed mechanism for this domino reaction