Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• reactions, yielding multicyanated ethenes [95]. Contrarily, alkenes bearing three or four ester substitutions partake in a [4 + 2]-type hetero-Diels–Alder (DA) reaction, yielding a third product, presumably through a [3 + 2] cycloaddition reaction, followed by rearrangement. The [2 + 2] CA–RE reactions

• equivalents of TCNEO relative to the alkyne substrate for the generation of the TCBD products [100]. For the reaction, the formal [3 + 2] cycloaddition reaction is postulated to initiate through the initial nucleophilic attack of the alkyne carbon on the electrophilic TCNEO carbon, yielding a zwitterionic

Morpholine-mediated defluorinative cycloaddition of gem-difluoroalkenes and organic azides

• Tzu-Yu Huang,
• Mario Djugovski,
• Sweta Adhikari,
• Destinee L. Manning and
• Sudeshna Roy

Beilstein J. Org. Chem. 2023, 19, 1545–1554, doi:10.3762/bjoc.19.111

• generated via an azide–alkyne cycloaddition or a multicomponent reaction between carbonyls and azides [17]. α-Trifluoromethyl (α-CF3) carbonyls were recently utilized to generate NH-1,2,3-triazoles and fully substituted 1,2,3-triazoles [28][29]. However, there are no reports of a formal [3 + 2

• ] cycloaddition reaction utilizing gem-difluoroalkenes, which inherently exhibit attenuated activity compared to the activated α-CF3 carbonyls. This report provides a highly regioselective and novel way to access C-4-morpholine-functionalized fully decorated 1,2,3-triazoles from gem-difluoroalkenes and organic

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• addition; [3 + 2] cycloaddition reaction; hydrosilylation reaction; N-heterocyclic carbenes; NHC–Cu complexes; NHC–Cu complexes as catalyst; Introduction N-Heterocyclic carbenes (NHCs) are a neutral species having the carbene carbon atom as a part of the nitrogen heterocyclic ring. The transient

• catalyst when products were obtained with excellent enantioselectivity (92% ee) (Scheme 46). 2.3 [3 + 2] Cycloaddition reactions In a [3 + 2] cycloaddition reaction, a three atoms dipolar moiety (1,3-dipole) adds across two atoms of an alkene or alkyne (1,3-dipolarophile) (Scheme 47). It is also known as

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• intermediate separations. Conclusion A readily and efficient four-component synthesis for spirooxindolepyrrolothiazoles is introduced, which involves a sequential N,S-acetalation and decarboxylative [3 + 2] cycloaddition reaction. This one-pot and two-step process with four components generates 5 bonds, 5

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• . Based on some experimental results, a suitable mechanistic pathway has been proposed (Scheme 1). At first, imidazole N-oxide underwent a [3 + 2] cycloaddition reaction with ylidene 5 to form unstable cycloadduct 6, which then rearomatized followed by ring opening to provide the intermediate 7. Finally

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• prevalent scaffold in biomedical research and drug discovery programs. We also proposed a plausible mechanism for the selectivity of the [3 + 2]-cycloaddition reaction to produce 3,4,5-trisubstituted isoxazoles. Not to be overlooked are our optimized reaction conditions for the dimerization of hydroximoyl

• for the selectivity of the [3 + 2]-cycloaddition reaction to produce 3,4,5-trisubstituted isoxazoles. Not to be overlooked is our optimized reaction conditions for the dimerization of hydroximoyl chlorides to form furoxans or 1,2,5-oxadiazole 2-oxides, a class of structures with important biological

• and extracted with ethyl acetate. The organic phase was washed with brine and dried with Na2SO4. The solvent was then evaporated under reduced pressure to produce the desired phenyl hydroximoyl chloride, which was used immediately for the [3 + 2]-cycloaddition reaction without further purification

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

• construction of bispirobarbiturates [30][31]. In 2019, for example, An and co-workers reported an asymmetric Michael/Mannich [3 + 2] cycloaddition reaction between N-(2,2,2-trifluoroethyl)isatin ketimines and barbiturate-based olefins (Scheme 1a) [32]. Based on the current knowledge, the construction of

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• -ium-2-ide (7a) was synthesised at room temperature by treating methyl acrylate, hydrazine hydrate and benzaldehyde in a yield of 67%. On treating the synthesised azomethine imine 7a (1.2 mM) and 2-substituted-1H-indenes 6b and 6c (1 mM) in toluene at 70 °C affords 8a and 8b via [3 + 2] cycloaddition

• reaction at a yield of 61% and 72%, respectively. Encouraged by the outcome of this non-catalytic cycloaddition reaction, similar studies using 2-substituted-1H-indenes (6a–f) with azomethine imines are underway. Conclusion In summary we have developed an efficient synthetic protocol for intramolecular

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

• for the reaction as both of the two selanyl groups are used [53]. Trisubstituted triazoles 93 containing an Sb substituent at position C5 were prepared via a Cu-catalyzed [3 + 2]-cycloaddition reaction between several ethynylstibanes 91 and benzyl azide 92 using CuBr under air. The reaction proceeded

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• ] developed a visible-light-induced [3 + 2] cycloaddition reaction between glycine derivatives 57 and aryl epoxides 58, which can efficiently prepare a series of multisubstituted 1,3-oxazolidines 59 at room temperature (Scheme 20). The strategy can be applied smoothly to an extensive range of glycine

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• Iwasawa and co-workers in 2011 [18][66] (Scheme 10A). Treatment of Boc-protected aniline 139 and n-butyl vinyl ether (140) with a platinum(II) catalyst afforded tricyclic indole 141 in 83% yield. The authors suggested that this catalytic [3 + 2] cycloaddition reaction may involve an α,β-unsaturated

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• area, reporting on the synthesis of the first heteroleptic bis-NHC and mixed NHC/phosphine copper(I) complexes [20][21][22]. Interestingly, these new copper-based complexes have shown excellent activity in the [3 + 2] cycloaddition reaction of azides/sulfonyl azides and alkynes (Scheme 1, right) [22

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• employment of isoxazole nucleophiles in gold-catalyzed formal [3 + 2] cycloaddition reaction of ynamides [31][32], and zinc-catalyzed the reaction of ynol ethers [33], giving the respective multi-substituted pyrrole derivatives efficiently (Scheme 2a) [34][35]. The reaction proceeds via an α-imino gold

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• diastereoselective [3 + 2] cycloaddition reaction [14][15]. The ring expansion sequence 1 → 2 → 6 → 8 has been used as a key step in the synthesis of (±)-fragranol [16], (±)-grandisol [16], (±)-α-cuparenone [17] and (±)-herbertene [17]. Aryl cycloropyl sulfides 1 are most frequently prepared by cyclopropylation of

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• cycloaddition chemistry based on compound 1. Zheng et al. [7] first reported on the [3 + 2] cycloaddition reaction of 1 with an alkene or alkyne mediated by visible light by the aid of the photocatalyst [Ru(bpz)3](PF6)2. Our group reported the metal catalyst itself, particularly the dinuclear rhodium complex

• biomedical research [25][26][27][28][29]. Thus, based on this cycloaddition protocol, a convenient strategy can be established to synthesize trans-cyclic β-amino acids. The mechanism of the [3 + 2] cycloaddition reaction of 1a and 2a is similar to that previously reported [18] (Scheme 3). The distonic

• -centered radical B, which continues to catalyzing the reaction. Conclusion In conclusion, we report on the [3 + 2] cycloaddition reaction catalyzed by dirhodium(II) based on arylcyclopropylamine, which broadens the scope of this method to the alkynyl group. This study demonstrated that this cycloaddition

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• have been used to build the hydrindane bicyclic system, but incorporating a different functionalization pattern in the cyclic compounds. Proposed here is a new methodological approach to functionalized 3a-substituted hydrindane synthesis based on a Danheiser annulation involving a [3 + 2] cycloaddition

• reaction of a (trimethylsilyl)allene and a suitable cyclic α,β-unsaturated ketone [30][31]. Despite the applicability of the reaction to construct five-membered rings, it has not been extensively examined [32] for the synthesis of complex natural products. As depicted in Scheme 2, the hydrindane core ring

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• ][1,4]diazepinium salts 10 and the related neutral, free bases 13 were synthesized from 4-acetoxy-1-acetyl-4-phenylazo-1,2,3,4-tetrahydroquinolines 8 and nitriles 9 in the presence of aluminium chloride by the [3+ + 2]-cycloaddition reaction of the in situ generated azocarbenium intermediates 14

• . Conclusion In summary, an appealing series of 1,2,4-triazole-fused 1,4-benzodiazepines 10 and 13 were prepared via the [3+ + 2]-cycloaddition reaction followed by a cationic [1,2]-rearrangement reaction. The procedure is general and has several advantages such as ready availability of starting materials

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

• Yasuhiro Yamashita,
• Susumu Yoshimoto,
• Mark J. Dutton and
• Shū Kobayashi

Beilstein J. Org. Chem. 2016, 12, 1447–1452, doi:10.3762/bjoc.12.140

• with other electrophiles. The [3 + 2] cycloaddition reaction of 0.5 M 1a (10 mmol) with 2 (11 mmol) was conducted at −40 °C for 18 h by using the chiral copper amide prepared from CuOTf·0.5toluene complex (0.011 mmol), KHMDS (0.010 mmol), and FeSulphos (0.011 mmol) in situ. Chiral copper amide

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• enals and a transition metal promoting to open the 2-vinylcyclopropanes for highly regio- and enantioselective [3 + 2] cycloaddition reaction of 2-vinylcyclopropanes with α,β-unsaturated aldehydes has been developed. Keywords: [3 + 2] annulation; enals; synergistic catalysis; vinylcyclopropanes

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

• prepare phosponylpyrazoles 217 in the presence of KOH in MeOH in 73–95% yields (Scheme 44) [82]. Based on their explanation, the treatment of dimethyldiazomethylphosphonate 213 with a nucleophilic base generates diazo compound 215. The subsequent [3 + 2] cycloaddition reaction of 215 with Knoevenagel

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• (CpRu) complexes containing tethered chiral sulfoxides were synthesized via an oxidative [3 + 2] cycloaddition reaction between an alkyne and an allylruthenium complex. Sulfoxide complex 1 containing a p-anisole moiety on its sulfoxide proved to be the most efficient and selective catalyst for the

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• the H-4a proton that resonates at 2.18 ppm as a doublet of doublet of doublets. 5’-Azido-2’-oxa-3’-aza-4’a-carbanucleosides 11 and 12 were independently engaged in a CuI-catalyzed Huisgen [3 + 2] cycloaddition reaction with a series of substituted alkynes 17, according to the procedure described by

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• several advantages over the classical C–C bond formation method including the stability and preparation of the starting material and the non-hazardous byproducts. In 2011, Kolarovič et al. [6] first reported the copper-catalyzed decarboxylative [3 + 2] cycloaddition reaction of 2-alkynoic acid with

Synthesis of 2-trifluoromethylpyrazolo[5,1-a]isoquinolines via silver triflate-catalyzed or electrophile-mediated one-pot tandem reaction

• Xiaoli Zhou,
• Meiling Liu,
• Puying Luo,
• Yingjun Lai,
• Tangtao Yang and
• Qiuping Ding

Beilstein J. Org. Chem. 2014, 10, 2286–2292, doi:10.3762/bjoc.10.238

• Gynecology, Jiangxi Provincial people's Hospital, Nanchang, Jiangxi 330006, P. R. China 10.3762/bjoc.10.238 Abstract An efficient one-pot tandem cyclization/[3 + 2] cycloaddition reaction of N’-(2-alkynylbenzylidene)hydrazides with ethyl 4,4,4-trifluorobut-2-ynoate under silver triflate-catalyzed or

• of this tandem cyclization/[3 + 2] cycloaddition reaction, a range of N’-(2-alkynylbenzylidene)hydrazides 1a–j were prepared from the corresponding aldehydes and applied to the synthesis of trifluoromethylated pyrazolo[5,1-a]isoquinoline derivatives 3 under the optimized conditions (Table 1, entry 8

• -coupling reaction. Conclusion In conclusion, we have developed an efficient one-pot tandem cyclization/[3 + 2] cycloaddition reaction of N’-(2-alkynylbenzylidene)hydrazides with ethyl 4,4,4-trifluorobut-2-ynoate under silver triflate-catalyzed or electrophiles-mediated conditions. Highly functionalized