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

• adduct leads to the formation of a spiro compound [89][90][91][92][93][94]. Ester-substituted, electron-deficient alkenes have also been employed in [2 + 2] CA–RE reactions involving electron-rich alkynes. Alkenes featuring either one or two ester substitutions exclusively catalyze [2 + 2] CA–RE

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• ). However, piperidine, TMG, and Na2CO3 failed to promote the annulation reaction (Table 1, entries 4–6). When triethylamine was employed as the base, the reaction gave the spiro compound 3a in 71% yield (Table 1, entry 7). The yields of product 3a remained nearly unchanged when the reaction time was either

• equivalent, the yield of spiro compound 3a decreased to 35% (Table 1, entry 17). At last, if the amount of α-halogenated acylhydrazone was reduced, the yield of product 3a also decreased to 57% yield (Table 1, entry 18). Thus, the best reaction conditions were carrying out the reaction in DCM at room

• cm−1; HRMS–ESI TOF (m/z): [M + Na]+ calcd for C34H28ClN4O3SNa, 595.1774; found, 595.1765. The crystallographic data of compound 7a (CCDC 2280223) have been deposited at the Cambridge Crystallographic Database Centre. Single crystal structure of the spiro compound 7a. Representative [4 + 3

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

• Scheme 1) [12]. In the presence of piperidine, the reaction in methanol at room temperature did not yield the product (Table 1, entry 1). However, the reaction in methanol at elevated temperature gave the expected spiro compound 3a in 51% and 48% yields, respectively (Table 1, entries 2 and 3). The

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• a result of the cycloaddition reaction with cyclopropene 2m. The corresponding bis-spiro compound 5a was readily isolated in 82% yield after recrystallization from ethanol. Similarly, we succeeded in carrying out reactions between unsymmetrically 1,2-disubstituted cyclopropenes 2n, 2o and PRP (1). 1

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

• intramolecular addition of the carbanion to the enone affords the cyclic intermediate (C), which in turn converts into the intermediate (D) by transfer of a negative charge. Finally, the spiro compound 3 is formed by elimination of tributylphosphine. When 3-(ethoxycarbonylmethylene)oxindole 4 is employed in the

• reaction, the nucleophilic addition of the zwitterion (A) to this compound takes place at the exocyclic position giving the adduct (E), which in turn proceeds with the intermediates (F) and (G) according to the above mentioned similar processes to give the spiro compound 5. The different addition direction

• ''-indoline] 8a as the major product. The loading of tri(n-butyl)phosphine played an important role for the formation of the products. When 2.0 equiv of P(n-Bu)3 were used, the reaction gave the spiro compound 8a in 71% yield. Thus, this reaction is not a simple catalytic reaction and tri(n-butyl)phosphine

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• cascade aza-Michael addition/olefin hydroalkylation reaction between N-tosylallylamines and α,β-unsaturated ketones using a catalytic system of a gold(I) complex and a silver salt [45]. The spiro compound 25, which was obtained in moderate yield and with poor diastereoselectivity after a 20 h reaction

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• proceeded with high levels of diastereocontrol. The resulting sulfonamide derivatives 95 were transformed into the target spiro compound 97 by performing successive desulfinylation and intramolecular palladium-catalyzed N-arylation. To rationalize the stereochemical course of the addition, DFT calculations

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• %). Finally, the spiro compound 30 was subjected to the SM coupling using two different boronic acids to produce the aryl substituted spiro compounds such as 31 (96%) and 32 (79%) (Scheme 4). Along similar lines, we have also demonstrated the synthesis of bis-spirocycles such as 37 by adopting a double RCM

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• ) in presence of 3.0 equivalents of TFA as an additive in dichloromethane (Scheme 17). The fused tricyclic compound 53 was obtained as major product in 55% yield along with the spiro compound 54 as a minor product in 8% yield. In 2009, Zhang and co-workers [89] reported an efficient method for the

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

• species from 2-aminopyridine and isatin which then undergoes a formal [4 + 1] cycloaddition with isocyanide to generate a spiro intermediate b. The spiro compound then undergoes a retro-aza–ene reaction via a [1,5]-hydride shift resulting in an aromatic imidazo[1,2-a]pyridine having an isocyanate

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• ring closing metathesis to afford the bicyclic product 53. Finally, the RCM of the 1,4-adduct resulting from the addition of 3-butenylmagnesium bromide yielded the spiro compound 54. Interestingly, the conversion of bicyclic compound 40 catalyzed by the same system also occurred selectively in the 4

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

• presence of n-BuLi provided styrylfuran 270 in 72% yield. The DA reaction of styrene derivative 270 with DMAD 129 at 40 °C yielded oxabridged compound 268. Another route to 268 involves a DA reaction of 265 with DMAD at 55 °C for longer reaction time (3 days) and sequential Wittig olefination. The spiro

• 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

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• induce a similar Claisen rearrangement starting from the original spiro compound 12 by heating a DMF solution from 40 °C to 110 °C failed, with only decomposition being observed at the higher temperatures. This suggests that the Claisen rearrangement is being catalysed by the Ru present from the Grubbs

• reasonable yield. We report here the optimisation of the synthesis of two heterocycles, the spiro compound 14 (65%) and the fused 7-membered ring product 17 (72%) – both these heterocycles are synthesised in one pot from a cheap and readily available starting material and represent an exceptionally efficient

• chemistry has been established with the production of the new heterocyclic system 31 from the spiro compound 12. Further application of this tandem methodology offers significant potential in heterocyclic synthesis. Promising in vitro antiplasmodial activity was indicated with a number of the spiro

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• seen from the X-ray structures, the former is the anti-spiro compound 24 (Figure 4) and the latter its syn-isomer 25 (Figure 5), with the former possessing the longer chromatographic retention time. Unfortunately, because of lack of material, no high quality NMR spectra of these two hydrocarbons could

One-pot four-component reaction for convenient synthesis of functionalized 1-benzamidospiro[indoline-3,4'-pyridines]

• Chao Wang,
• Yan-Hong Jiang and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2014, 10, 2671–2676, doi:10.3762/bjoc.10.281

• molecular structure of spiro compound 1k (Figure 1), it can be seen that the four carbon atoms and the nitrogen atom in the newly formed 1,4-dihydropyridyl ring exist nearly in one plane, while the C-4’ atom slightly deviates in this plane (0.318(4) Å). The phenyl group of the oxindole moiety and the 1

• '-picolinamido group exist in the same side of the 1,4-dihydropyridyl plane. By observing the crystal structure of spiro compound 1k, we could conclude that the 1'-picolinamido group might exist in cis- or trans-position of the phenyl group of the oxindole moiety. Thus, the cis/trans-conformations are in a

• tautomerization results in the final spiro compound 1. In this process, the initially formed zwitterrionic intermediate (A) does not cyclize to give pyrazolone intermediate as in the reaction of hydrazine with acetylenedicarboxylate. Thus, benzohydrazide shows very different reactivity to that of hydrazine in the

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• -ylidenes spontaneously dimerize under ring cleavage of one of the N,N-bonds and ring closure to an indazole–indole spiro compound which possesses an exocyclic imine group. The E/Z isomers of the imines can be separated by column chromatography when methanol is used as eluent. We present results of a single

• observable in NMR spectra at standard temperature conditions. The spiro compound 14c crystallized from a saturated solution in n-hexane so that we were able to perform a single crystal X-ray analysis. The compound crystallized monoclinic. As expected, neither the pyrrole ring nor the pyrazole ring is planar

Facile synthesis of functionalized spiro[indoline-3,2'-oxiran]-2-ones by Darzens reaction

• Qin Fu and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 918–924, doi:10.3762/bjoc.9.105

• ]+ calcd for C23H17NNaO3, 378.1101; found, 378.1103. Molecular structure of spiro compound 3c. Molecular structure of spiro compound 4a. Molecular structure of spiro compound 5o. Synthesis of spiro-epoxyoxindole with pyridinium ylide. Reaction of 5-methylisatin (1) with phenacyl bromide (2). Synthesis of

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• arylamines and other primary amines. Keywords: 1,4-dihydropyridine; electron-deficient alkyne; four-component reaction; isatin; one-pot reaction; spiro compound; Introduction β-Enaminones and β-enamino esters represent important synthetic building blocks for the development of versatile carbon–carbon bond

• molecular structure of the spiro compound 3b shown in Figure 4, we could clearly see that the cyano group and the phenyl group of oxindole moiety in the newly formed dihydropyridinone ring exist in cis-configuration. 1H NMR spectra of 3a–3n all display one singlet at about 5.40 ppm for the one proton in the

• intermediate A with isatinylidene derivative B to yield intermediate C. In the case of the reaction containing malononitrile, the nucleophilic addition of the amino group to the C–N triple bond in intermediate C resulted in spiro compound 1 with the tautomerization of the imino group to an amino group. In the

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

• Yan Sun,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 8–14, doi:10.3762/bjoc.9.2

• scope of this novel reaction is briefly discussed. Keywords: arylamine; cyclopentanedione; isatin; multicomponent reaction; spiro compound; Introduction The spirooxindole is among the most important class of naturally occurring substances, characterized by highly pronounced biological properties, and

• be separated from the reaction system. On the other hand, the reaction of α-naphthylamine also gave good yields of spiro compound 1l (Table 1, entry 12). The structures of spiro compounds 1a–1l were fully characterized by 1H and 13C NMR, HRMS, and IR spectra and were further confirmed by a single

• second equivalent of cyclopentane-1,3-dione gave the double condensation product 3. On the other hand the carbonyl ion B reacted with the arylamine to give intermediate C. Then the intramolecular dehydration of C resulted in the final spiro compound 1 or 2. In this reaction process the reactivity of

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• produce the (+)-DMDP (49) and (−)-bulgecinine (50) (Scheme 8). The starting point in the synthesis of (+)-broussonetine G, 53, was the same annulated oxazolone 48 which, after conversion into the Weinreb amide 51, was coupled with the alkyl bromide substituted spiro compound 52 (Scheme 9). In fact, the

The arene–alkene photocycloaddition

• Ursula Streit and
• Christian G. Bochet

Beilstein J. Org. Chem. 2011, 7, 525–542, doi:10.3762/bjoc.7.61

• completely new reaction Sakamoto has proposed a mechanism involving a ζ-hydrogen abstraction to form a biradical intermediate (Scheme 35, E). The resulting biradical cyclizes to form the spiro compound F upon recombination of the biradical. Re-aromatization affords the carboxylate G, which further attacks

• can take place to form a spiro compound; further re-aromatization to form the enol, lactolization and cyclization explains the formation of the benzoxepine structure [101]. Griesbeck et al. reported the formation of benzoxepines from the benzophenone analogue upon irradiation at slightly lower

A stable enol from a 6-substituted benzanthrone and its unexpected behaviour under acidic conditions

• Marc Debeaux,
• Kai Brandhorst,
• Peter G. Jones,
• Henning Hopf,
• Jörg Grunenberg,
• Wolfgang Kowalsky and
• Hans-Hermann Johannes

Beilstein J. Org. Chem. 2009, 5, No. 31, doi:10.3762/bjoc.5.31

• stable enol 4, which is converted by dehydrogenation into the benzanthrone derivative 7. Under acidic conditions 4 isomerises to the spiro compound 11 and the bicyclo[4.3.1]decane derivative 12. Furthermore, the formation of 7 and the hydrogenated compound 13 is observed. A mechanism for the formation of

• under these reaction conditions. Spiro compound 11 (11% yield) was characterised by NMR spectroscopy, mass spectrometry and single crystal X-ray crystallography (see below). The 1H NMR spectrum (600 MHz) of 11 shows two aliphatic triplets at δ = 2.16 and 3.42 ppm (J = 6.2 Hz) which are assigned to the

• internal Friedel-Crafts alkylation provides the spiro compound 11. Alternatively, protonation of 4 at C-5 generates the benzylic cation 17, which by intramolecular electrophilic attack leads to the bicyclo[4.3.1]decane derivative 12. Finally, the formation of 13 is a formal hydrogenation of the starting