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

• -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

• to produce 157. Following this, β-hydride elimination occurs yielding the final product 152 and a Rh(I) species which is oxidized back to its active Rh(III) state by Cu(OAc)2·H2O. In 2017, Radhakrishnan reported a Rh-catalyzed annulation of O-acetyl ketoximes 159 or N-methoxybenzamides 161 with

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• favoring reactivity with various types of substrates, ranging from halides to carbonyls and alkenes/alkynes. It is comprehensible that this reagent attracted early interest in natural product synthesis and more precisely on medium-sized ring formation. 4.1 SmI2-mediated Barbier-type ring annulation towards

• -mediated cyclization as a key step of the synthesis [68]. Indeed, this pivotal annulation step was conducted on aldehyde 142 prepared from (+)-trans-dihydrocarvone (141) and yielded the expected complex tricyclic [5-8-6] alcohol 144 in 93% with a high diastereoselectivity (dr 23:1). Of note, the reaction

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• activation/annulation cascade of readily available enaminones with iodonium ylides towards the convenient synthesis of isocoumarins. This coupling system proceeds in useful chemical yields (up to 93%) via a cascade C–H activation, Rh-carbenoid migratory insertion and acid-promoted intramolecular annulation

• of 1,2-difunctionalized arenes with alkynes or carbon monoxide (Scheme 1b, III) [13][14][15][16], have been widely applied for the assembly of isocoumarins over the past decades. Recently, the transition-metal-catalyzed ortho C–H activation/annulation of benzoic acids has emerged as an attractive

• preparation of manuscript, the group of Li reported a similar Rh(III)-catalyzed [3 + 3] annulation of enaminones with iodonium ylides [32]. Inspired by the collected contributions [26][27][28] and based on our ongoing research in C–H activation [33][34][35], we recently wondered whether it might be possible

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• ’-methoxy-γ-pyrone in one step. To construct the quaternary carbon of the 2,5-cyclohexadienone of the target, a strategy based on the Robinson-type annulation of an aldehyde derived from α-crotyl-α’-methoxy-γ-pyrone was applied. The grafting of the simplified target’s side chain was demonstrated through an

• oxidative anionic oxy-Cope rearrangement of the tertiary alcohol arising from the 1,2-addition of a 1,3-dimethylallyl reagent to 2,5-cyclohexadienone connected to the α’-methoxy-γ-pyrone motif. Keywords: α’-methoxy-γ-pyrone; 2,5-cyclohexadienone; oxy-Cope; quaternary carbon; Robinson-type annulation

• to 2,5-cyclohexanedione 5 was accordingly updated and an approach to make use of the Robinson-type annulation was devised from aldehyde 9, prepared by oxidation of α-crotyl-α’-methoxy-γ-pyrone 8 (Scheme 4). While its synthesis was initially investigated by the coupling of tri(n-butyl)crotylstannane

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• addition (if X = H) or proton cleavage in the case of X = OH. Amine mediators are also suitable for the generation of radical species from CH-acidic substrates, such as β-dicarbonyl compounds. This reactivity was used in the dehydrogenative annulation of N-allyl amides with β-dicarbonyl compounds with the

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• heterocyclic systems are heteroanalogues of antimicrobial and antibiofilm fungal metabolites. The developed reaction represents the first example of involving 1H-pyrrole-2,3-diones fused at the [e]-side in a [4 + 1] annulation reaction. Keywords: [4 + 1] annulation; catalyst-free; diazooxindole; 1H-pyrrole

Scope of tetrazolo[1,5-a]quinoxalines in CuAAC reactions for the synthesis of triazoloquinoxalines, imidazoloquinoxalines, and rhenium complexes thereof

• Laura Holzhauer,
• Chloé Liagre,
• Olaf Fuhr,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2022, 18, 1088–1099, doi:10.3762/bjoc.18.111

• investigated and the denitrogenative annulation towards imidazoloquinoxalines could be observed as a competing reaction depending on the alkyne concentration and the substitutions at the quinoxaline. Keywords: click reaction; CuAAC; denitrogenative annulation; imidazole; metal complexes; quinoxaline

• imidazole-fused products via denitrogenative annulation leading to 2 is, compared to the ever-present CuAAC, less known and was only shown with one example so far [11]. The study described herein intends to investigate the reactivity of tetrazolo[1,5-a]quinoxalines 1 concerning the competing formation of

• annulation was observed as a competing reaction, leading to imidazole product 16. This competing reaction was also observed for an aromatic alkyne (see Supporting Information File 1), but did not occur in any of the previous experiments with unsubstituted tetrazolo[1,5-a]quinoxalines. Moreover, the

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

• furnished a chiral thiosquaramide-catalyzed tandem Michael–Henry reaction of phenacylmalononitriles and nitroolefins for the enantioselective synthesis of cyclopent-3-ene-1-carboxamides [32] (reaction 2 in Scheme 1). Mohanan and co-workers reported a PBu3-catalyzed [3 + 2] annulation of

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• oxidation/degradation. In this paper we describe the cathodic generation and accumulation of NHC in a divided flow cell and its subsequent use as organocatalyst in the self-annulation of cinnamaldehyde and in the esterification of cinnamaldehyde. Results and Discussion Cathodic NHC generation and

• in a continuous flow electrochemical process, the flow methodology was applied to the self-annulation of cinnamaldehyde, a classical NHC-catalyzed reaction (Scheme 4). All the experiments were carried out using a solution of 0.1 M BMImBF4 in acetonitrile (20 mL) as catholyte, stainless steel as

• electrochemically generated NHC into the corresponding thione by its reaction with elemental sulfur. Umpolung of the aldehyde carbonyl carbon atom. Formation of the Breslow intermediate using NHCs. Electrogenerated NHC-catalyzed self-annulation of cinnamaldehyde. Byproduct obtained from the reaction between

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• synthetic strategies are cyclization reactions and annulation reactions. The cyclization reactions have been applied in the construction of any ring bonds of 1,2-azaphospholidine and 1,2-azaphospholine rings, while [4 + 1] and [3 + 2] annulations are alternative routes for the formation of 1,2

• 1,2-azaphospholidine 2-oxides and their fused derivative, [4 + 1] annulations and more occasionally a [3 + 2] annulation. [4 + 1] Annulation via formations of both C–N and N–P bonds Miles and Street prepared 2-aryl/dimethylamino-1-ethoxy-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxides 201 from 2

• proceed due to their reduced nucleophilicities, generating the corresponding phosphonamidates only through the reaction with the more electrophilic phosphonochloridate (Scheme 32) [57]. [4 + 1] Annulation via formations of both C–P and P–N bonds (1S,3R)-2-(tert-Butyldiphenylsilyl)-3-methyl-1-phenyl-2,3

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

• . Additionally, the tri(n-butyl)phosphine-promoted domino annulation reaction of isatins and ethyl isatylidene cyanoacetates produced spiro[indoline-3,2'-furan-3',3''-indolines] in satisfactory yields. Keywords: isatin; spiro[cyclohexane-1,3'-indoline]; spiro[indoline-3,2'-furan-3',3''-indoline]; spirooxindole

• compounds [60][61][62][63][64][65][66] and in order to demonstrate the potential synthetic value of the nucleophilic phosphine-catalyzed annulation reaction, herein we wish to report the tri(n-butyl)phosphine-catalyzed reaction of isatylidene malononitriles and bis-chalcones for the synthesis of

• employed in the reaction. However, the reaction did not proceed to give the expected spiro[cyclohexane-1,3'-indoline], while a new spiro[indoline-3,2'-furan-3',3''-indoline] was obtained, which was clearly constructed from the annulation reaction of isatin with ethyl isatylidene cyanoacetate. Therefore, we

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• demethoxycarbonylating annulation of methyl methacrylate (33) with 3-cyanophthalide (32), in the presence of lithium tert-butoxide as catalyst (64% yield) (Scheme 7) [91]. Recently, Dissanayake and co-workers tested the stability of furans to be used as a diene in Diels–Alder reactions for the synthesis of p

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• approaches toward such compounds have been developed. Among these, cyclization and annulation of 3,5-unsubstituted, 4-substituted indoles involving an electrophilic aromatic substitution (SEAr) as the ring closure are particularly attractive, because they avoid the use of 3,4- or 4,5-difunctionalized indoles

• summarizing recent relevant literature reports. Keywords: annulation; cyclization; fused indoles; regioselectivity; SEAr; Introduction Over the decades, countless cyclization and annulation reactions of substituted arenes/heteroarenes involving an electrophilic aromatic substitution (SEAr) reaction as the

• constraints do not normally allow meta or para-selective cyclization/annulation. In certain such cyclization and annulation reactions, however, formation of the CAr–C bond at the ortho position is not guaranteed. As an example, cyclization and annulation of 3,5-unsubstituted, 4-substituted indoles involving

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• been recognized as chiral organocatalysts as early as 1912, the concept was at the periphery of the attention of synthetic organic chemists. An initial flash of interest appeared in the 1970s when proline was shown to catalyze the Robinson annulation [1][2], but this seminal work seemed to come too

• nitromethane to β-silyl α,β-unsaturated carbonyl compounds catalyzed by bifunctional squaramide catalysts are effective under solvent-free conditions [26]. Zhai and Du demonstrated that asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins are efficiently

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• Jiang-Song Zhai Da-Ming Du School of Chemistry and Chemical Engineering, Beijing Institute of Technology, No.5 Zhongguancun South Street, Beijing 100081, People’s Republic of China 10.3762/bjoc.18.3 Abstract Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2

• loading on the reaction (Table 1, entries 9–16). The experimental results show that the solvent has a non-negligible effect on the reaction and dichloromethane (DCM) has the best reaction effect in the annulation system (Table 1, entries 9–15). Hereafter, we tried to reduce the catalyst loading to further

• organocatalytic domino Michael/cyclization reaction. This annulation reaction can be easily performed under air atmosphere and mild conditions with 5 mol % catalyst loading. By using bifunctional thiourea catalyst, a series of structurally diverse indanone-derived spirobarbiturates could be obtained in high

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

• a net iminyl-nitrooxylation reaction [140]. In 2020, Wei and co-workers studied an iminyl radical-triggered 1,5-hydrogen atom transfer (HAT) and [5 + 2] annulation processes for the synthesis of azepine derivatives 170 (Scheme 36) [141]. The reaction was tolerable of both electron-donating and

• electron-withdrawing substituents on the oxime; however, the reaction required highly activated alkenes to proceed. 1,2-Disubstituted alkenes were tolerated and were diastereoselective for the anti-addition product. When maleimides 171 were used as the 2-carbon coupling partner, a [5 + 1] annulation was

• different coupling partners, both bi- [142] and tricyclic [143] fused heterocyclic frameworks have been synthesized through iminyl radical cascade cyclization and annulation reactions. Carbooxygenation In 2017, the Bao group reported the first decarboxylative alkyl etherification of alkenes 108 with

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• halogenoketones or ketocarboxylic acids upon action of SnCl2·H2O, TiCl4/Zn, or Fe/CH3COOH can be mentioned [28][29][30]. 1-Aryl-substituted tetrahydropyrrolo[1,2-a]quinazolin-5-ones can be also obtained by a Brønsted acid-catalyzed annulation of arylcyclopropane aldehydes and N′-anthranilic hydrazides [31], as

• ring (especially with functional groups) is annulation of the latter moiety to the quinazoline ring. Thus, a series of 1,5-disubstituted pyrroloquinazolines 3 were obtained by a three-component Sonogashira-type coupling of 2-chloro-4-substituted quinazolines 4, propargylic alcohol, and secondary amines

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• ]. Zhou and co-workers published an excellent paper in 2019 on the conversion of central to axial chirality in an enantioselective [3 + 2] annulation of 1-styrylnaphthols 32 with azonaphthalenes 33. Under defined conditions, the cycloaddition product 34 was prepared in high yield (99%) with exclusive

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• ][35][36]. In this context, Huang, Fu and co-workers reported carbene-catalyzed enantioselective formal [4 + 2] annulation reactions of β-silyl enones with enals and with active acetic esters (Scheme 1g) for the preparation of chiral organosilanes [34][35][36]. Very recently, during the final stage of

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• . In this work, N,N-dialkylanilines or N-aryltetrahydroisoquinolines 48 reacted with N-substituted maleimide 49 via annulation to provide a range of tetrahydroquinolines or tetrahydroisoquinolines 50, respectively, with good yield. The mechanistic investigation revealed that an α-amino radical

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• in 2020, an enantioselective C–H annulation of ferrocenylformamides with alkynes was achieved by the Ye group enabled by Ni-Al bimetallic catalysis and a chiral secondary phosphine oxide (SPO) ligand [35]. Hou et al. also reported the asymmetric C−H alkenylation of quinoline- and pyridine-substituted

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

• , Jiangxi Provincial People’s Hospital Affiliated to Nanchang University, 92 Aiguo Road, Nanchang, Jiangxi, 330006, China 10.3762/bjoc.17.163 Abstract Great progress has been made in the tandem annulation of enynes in the past few years. This review only presents the corresponding reactions of 1,3-enyne

• introduce the applications of the products and the reaction mechanisms for the synthesis of corresponding N-heterocycles. Keywords: 1,3-enyne; functionalization; pyridine; pyrrole; tandem annulation; Introduction The pyridine moiety is an important class of six-membered N-heterocycles that is widely found

• pyridine derivatives have been developed through the intramolecular or intermolecular tandem addition annulation/functionalization of alkynes with some N-containing compounds, such as nitriles, oximes, and imines [15][16][17][18][19]. The pyrrole structural motif is also an invaluable five-membered N

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• intramolecular cyclization until 2012 [52]. Mohanakrishnan’s group has contributed with numerous methodologies for the synthesis of anthracene derivatives, mainly methodologies involving Lewis acid-mediated intramolecular cyclizations. For example, in 2012 they reported an annulation protocol to synthesize

• anthracene, tetracene, and naphtho[b]thiophene derivatives via ZnBr2-mediated regioselective annulation of asymmetric 1,2-diarylmethine dipivalates 83a (Scheme 20). On the basis of this methodology, they prepared 37 examples of different types of anthracene derivatives, such as compounds 84a–e, in very good

• the representative examples 194a–d [81]. In 2017, Mal and Basak applied a [4 + 2] anionic annulation of substituted cyanophthalides 195 with dienoates 196 and obtained 3-allylnaphthoates 197 (Scheme 46) [82]. Then, they converted the naphthoate derivatives 197 to the corresponding alcohols 198 by

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• takes place to form intermediate 22, which subsequently converts to diazo-functionalized intermediate 23. Finally, the intramolecular annulation of intermediate 23 gives corresponding fully decorated 1,2,3-triazole 19 (Scheme 9) [42]. A domino coupling synthesis of fully decorated 1,2,3-triazole

• converted to fused sultams (Scheme 30) [56]. Anand et al. reported a Cu-catalyzed one-pot method for the preparation of 1,2,3-triazole-fused tricyclic heterocycles 106 via an intramolecular [3 + 2]-annulation. This strategy includes the 1,6-conjugate addition of Me3SiN3 to o-alkynylated p-quinone methides

• 105, followed by an intramolecular Click annulation to provide rapid access to a wide range of desired 1,2,3-triazole-fused isoindolines 108 with a reasonable yield. The reaction was carried out well by using o-alkynylated p-quinone methides 105 and TMSN3 in the presence of a catalytic amount of CuOTf