A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• series of reactions like the carbonyl–ene cyclization of (S)-citronellal preferentially to isopulegol, the water elimination from 1,1-diphenylethanol, the isomerization of α-pinene and β-pinene preferentially to limonene and minor amounts of camphene. The role of the supramolecular catalyst consists in

• reactions involving the formation of cationic intermediate species [41] like water elimination from an alcohol to provide the corresponding alkene, the isomerization of β-pinene and α-pinene and the cyclization of (S)-citronellal to secondary alcohols. The key point to interpret the action of the capsule in

• performed extra control experiments for each investigated reaction also only with the more symmetrical and less acidic capsule A to underline the effect of the water content on the catalytic activity. (S)-Citronellal isomerization to cyclic secondary alcohols (S)-Citronellal is an enantiopure monoterpenoid

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

• nine-membered rings 27 via triflic acid (TfOH)-catalyzed reaction of indole-derived phenylenediamine 25 with aldehydes 26 (Scheme 9) [19]. Mechanistically, the initially formed iminium ion I undergoes isomerization to iminium ion II through a 1,3-hydride shift process. Iminium ion III could then be

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• previously put forth by Nishimura and co-workers [64]. Isomerization of the oxabicyclic starting material to 17 may operate through a similar process described at Hill and co-workers (Scheme 1) [61]. Irreversible C–O insertion of the chloroiridium(I) species at the more electron-dense C1-position affords an

• enyliridium(III) alkoxide complex which eventually leads to the formation of isomerized 1-naphthol products [61]. Interestingly, the loading of the iridium precatalyst (Table 1, entries 11–13) also had a substantial effect on the isomerization of 13b, with increased loading producing more byproduct. Other

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• possible to identify three alternatives for the functionalization of β-NQS with amines: a) substitution of sulfonate by secondary amines; b) substitution of sulfonate by primary amines, followed by isomerization; and c) double addition of primary amines. In addition, other nucleophiles can also be used

• isomerization involves two routes: one through the hydrolysis of 22 leading to lawsone (4) and the subsequent addition of arylamines in position C2, and the other involves the addition of arylamines at position C2 of 22, leading to 24 with two equivalents of arylamine, which after hydrolysis of the imine at

• important natural and synthetic naphthoquinones. Drugs detected using β-NQSNa. Modifications that can be easily carried out from the products of β-NQS 8. Synthetic studies of BNQs and reactions with amines. Methods described for the synthesis of β-NQS. Reactions between β-NQS and amines. Isomerization of 4

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

• authors believe this reaction likely proceeds with the σ-aryliron intermediate 42 cyclizing to give the η1-allyliron species 45. Isomerization of 45 would deliver the less-hindered isomer 48 (path i). The stereochemical outcome can be rationalized by the steric interactions of the iron residue and the C–H

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

• 69 and 70 in high yields (up to 89%) with excellent enantioselectivity (up to 98% ee, Scheme 22) [78]. The primary amino group in the N1-(aryl)benzene-1,2-diamines reacts with the carbonyl group in 67 to give imine intermediate I-15 mediated by the chiral phosphoric acid. Meanwhile, isomerization of

• -naphthol (88) and allene-iminium intermediate I-24 to form axially chiral I-25, followed by rearomatization of the naphthol ring of I-25 and isomerization to I-26. Thereafter, CPA forms two hydrogen bonds with the two OH groups of I-26 to generate a carbocation and facilitates an intramolecular

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• transesterification to give the hemithioacetal 39, which cyclized to the oxathiolane 40 in situ with minor isomerization. The reduction of the ester group with LiAlH4, followed by benzoylation using benzoyl chloride and pyridine gave 1,3-oxathiolane derivative 41. Kraus and Attardo [48] developed new strategies for

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• -diaryl-substituted enamides is observed. Thus, the method provides synthetic access to both isomers of the target enamides from (Z)-β-enamido triflates. Keywords: enamides; isomerization; Suzuki–Miyaura coupling; vinyl triflates; Introduction Enamides are substrates of high value in organic synthesis

• isomerization of N-allyl amides [20], but still possess drawbacks, especially for stereoselective synthesis of tri- and tetrasubstituted enamides. Recently, we have reported a triflic acid-mediated reaction of N-fluoroalkyl-1,2,3-triazoles leading to (Z)-β-enamido triflates [21] and Lewis acid-mediated reaction

• were found to undergo cross-coupling reactions with retention of configuration on the double bond and served as valuable starting materials for the synthesis of functionalized β,β-disubstituted enamides (Scheme 1A) [21][23]. In the last decade, only a few reports describing isomerization of the double

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• Scott Benz Andrew S. Murkin Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York 14260-3000, United States 10.3762/bjoc.17.172 Abstract In the presence of a suitable acid or base, α-hydroxyaldehydes, ketones, and imines can undergo isomerization that

• -promoted steps, beginning with a vinylogous α-ketol rearrangement to 46. Following protonation of the enolate and addition of hydroxide to the carbonyl on the D ring, 47 rearranges with loss of chloride to give enedione 48. Base-catalyzed isomerization yields 44, which is apparently more stable despite the

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• isomerization to the Z-isomer (Z)-15a, which is required for cyclization, proceeds through the protonated intermediate 20, in which the weakened double bond permits configurational equilibration between the geometric isomers [20] (Scheme 3). Alternatively, a purely thermal E-to-Z isomerization of the enaminone

• prior to acid-promoted cyclization cannot be ruled out, since conjugation in the push–pull system should weaken the C=C bond and lower its rotational barrier [20]. Similar enaminone isomerizations have been detected even at room temperature [48]. If thermal isomerization indeed takes place, then one

• (vinylogous cyanamides) has also been described [53]. A similar base-induced cyclization of N-(alkoxycarbonylmethyl)-7-formylindoles to give pyrrolo[3,2,1-hi]indoles is also of interest [54]. Acid-induced cyclization akin to ours, and also assuming an in situ E to Z isomerization under the reaction conditions

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

• (Scheme 10) [52]. The tandem reaction involved a regio- and chemoselective addition of the Blaise reaction intermediate to 1,3-enyne, and the following sequential processes: isomerization, cyclization, and aromatization. Both carbocyclic and acyclic 1,3-enyenes 28 were compatible to give the corresponding

• products 52 were obtained efficiently through the cascade reactions of enynals 51, primary amines, aliphatic isocyanides, and trimethylsilyl azide. The following reaction involves Ag-catalyzed intramolecular 5-endo-dig cyclization and base (DMAP)-promoted oxidative isomerization. The presence of DMAP is

• previously reported methods is proposed in Scheme 22. Firstly, the hydrocupration of enyne 54 with LCuH 57 provides propargylcopper intermediate 58. The 1,3-isomerization of 58 and the following nitrile addition produces imine intermediate 60, which subsequently undergoes intramolecular cyclization, a 1,5

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• . Unexpectedly, olefin isomerization occurred which led to the formation of brevipolides M (13) and N (15) after treatment with titanium tetrachloride in ≈85% yield each. Biological activities The extracts of Hyptis brevipes Poit. have been utilized by humanity across the world in tropical regions ranging from

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• . The Hg(OTf)2-catalyzed isomerization of the double bond in compound 205 yielded thermodynamically favorable isomer 206 as a major product [123]. In 2010, Ravindar et al. developed the total synthesis of the steroidal natural product hippuristanol (211) starting from 11-ketotigogenin 208 (Scheme 63

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

• published in 2018, de Koning and co-workers reported a new methodology to synthesize the benzo[a]anthracene skeleton of angucycline derivatives 146 by using a multistep strategy based on Suzuki–Miyaura, isomerization, and ring-closing metathesis reactions (Scheme 33) [67]. The commercially available 2

• Wittig reaction affording naphthalenes 144. Isomerization of compounds 144 produced substituted styrenes 145. With the styrenes 145 in hands, the authors employed the Grubbs II catalyst-promoted ring closure to obtain the benzo[a]anthracenes 146a (85% yield) and 146b (43% yield) [67]. Other procedures In

• . AuCl-catalyzed double cyclization of diiodoethynylterphenyl compounds. Iodonium-induced electrophilic cyclization of terphenyl derivatives. Oxidative photocyclization of 1,3-distyrylbenzene derivatives. Oxidative cyclization of 2,3-diphenylnaphthalenes. Suzuki-Miyaura/isomerization/ring closing

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

• cycloisomerization of diolefins triggered by the MHAT process. Some challenges associated with the development of these reactions were the reversible nature of the HAT and the competition with linear isomerization and reductive pathways (Scheme 18) [72][73]. In 2014, the Shenvi group developed an olefin

• isomerization protocol triggered by an MHAT process using salen cobalt complexes as catalysts to furnish isomerized and cycloisomerized products (Scheme 19) [72]. Five and six-membered carbocycles containing quaternary carbon centers were synthetized in good to excellent yields and with excellent

• diastereoselectivity in the synthesis of bicyclic compounds (dr > 20:1, Scheme 19, 37d, 37e, and 37g). Substrates containing Lewis base moieties (Scheme 19, 36k) were tolerated in the reported reaction conditions, thereby representing a synthetic gain over other olefin isomerization methodologies. An important feature

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• . Moreover, the photoconversion yield for the E→Z isomerization is quantitative (within the detection limit of UV and NMR spectroscopy). A high efficiency in switching the biological activity off is important to avoid side effects of residual concentrations of the active form [13]. Water solubility and high

• to unsubstituted diazocines 10c and 11c. The activation barrier (EA) of the E→Z isomerization (obtained by an Arrhenius plot) is higher in formylated compounds 11 compared to acetylated compounds 10 and is further increased by halogenation. The unsubstituted N-formyl diazocine 11c and brominated NAc

• -diazocine 10a were also investigated in pure water since they are water-soluble (11c: ≈250 µM, 10a: ≈150 µM). The highest Z→E conversion yields are observed by irradiation with 400 nm in water and the back-isomerization E→Z can be accomplished by irradiation with light in the range of 525 and 600 nm (Figure

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

• Ivan P. Mosiagin,
• Olesya A. Tomashenko,
• Dar’ya V. Spiridonova,
• Mikhail S. Novikov,
• Sergey P. Tunik and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

• could be performed only with AlCl3 under harsh conditions and, therefore, cannot be used for the preparation of compounds with acid-sensitive substituents. In addition, the debenzylation of 1-benzyl-3-arylpyrido[2,1-a]pyrrolo[3,2-c]isoquinolines A was found to accompany by isomerization to 2-aryl

• ]isoquinoline backbone from N-unprotected pyrrolylpyridinium salts and, unlike the Pd-catalyzed version cyclization, avoids the deprotection step that is accompanied by isomerization. Molecular structure of compound 3a, displacement parameters are drawn at 50%. Molecular structure of compound 13, displacement

• [3,4-c]isoquinolin-4-ium bromide 8. Free-radical cyclization of dihalogeno-substituted salts 9 and 12. N-alkylation of the base 6a. Isomerization of compounds 17a and 18a. N-Alkylation of compounds 18a and 19. Optimization of the reaction conditions for the cyclization of 1a with TTMSS/AIBN in MeCN

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• ethylmagnesium bromide (Scheme 7c) [16]. The nucleophilic substitution of the halide on the magnesium atom with the carbenoid carbon atom having a halogen substituent is a plausible mechanism for the isomerization. The FBW rearrangement of magnesium alkylidene carbenoids was studied by using DFT calculations

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• ]triazine derivatives. In this regard, the possibility of prepearing esters 5 with an angular structure on the basis of directed isomerization of linear imidazo[4,5-e]thiazolo[3,2-b]triazines 4a–n in basic media has been studied. Indeed, boiling ethyl ester 4h in methanol in the presence of 0.5 equiv of a

• 1,3-diethylimidazo[4,5-e]thiazolo[3,2-b]triazines 4a,b,h,i upon treatment with an equivalent amount of triethylamine in corresponding alcohols proceeded without hydrolysis of ester groups and led to the formation of the corresponding regioisomeric derivatives 5a,b,h,i (Scheme 4). The isomerization of

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• also obtained by H-shift isomerization following the inverse electron-demand Diels–Alder reaction of tetrazines with p-quinone dibenzosuberenone. Then these pyridazines were converted to the corresponding pyrroles by reductive treatment with zinc. It was observed that all the dihydropyridazines

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• lactam 13nA (Scheme 3, insert). The relative configuration of the compounds 12m,n was determined by analogy, by ROESY investigations for the keto lactams 13m,n, and by isomerization experiments for 12n (vide infra). Amides 9o,p with cycloalkenyl substituents on the nitrogen were transformed to fused

• also occurred exclusively at the convex face of the bicyclic system. The configurations of the fused lactams were assigned by chemical derivatization and NOE experiments (vide infra). Functionalization reactions of lactams 12 Base-mediated isomerization reactions Lactams 12 are mixtures of two, four

• trans-12b can be also easily deprotected by a rhodium-catalyzed isomerization to the corresponding N-propenyl lactam followed by osmium tetroxide-catalyzed oxidative cleavage, providing lactam trans-17 in 62% yield. Additionally, the diastereomeric mixture of lactam 12o was subjected to oxidative N–O

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• . This observation suggests that lutidine allows the isomerization of 90 into 93, followed by a nucleophilic attack of the solvent at the sulfur atom (Scheme 25). The reactivity of analogous monotrifluoromethyl-substituted allyl derivatives 94, bearing an aryl group in the vinylic position was also

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• isomerization [36]. Several nitrogen nucleophiles have been evaluated as catalysts to promote the difluorocarbene formation from TFDA in order to bring about the cyclopropanation of a 2-siloxybuta-1,3-diene derivative; 1,8-bis(dimethylamino)naphthalene (proton sponge) was found to be particularly effective [37

• isomerization of trans-1,2-dichloro-3,3-difluorocyclopropane (84) (Scheme 37) [82]. Further research in this area was performed by the groups of Jefford [83] and Dolbier [84], who studied the 1,1-difluoro-2,3-dimethylcyclopropanes 86 and 87 (Scheme 38). Dolbier found that geminal fluorine substituents lowered

• the activation energies for both cis–trans-isomerization and for the transformation of vinylcyclopropanes into cyclopentenes. Both processes could occur by a C–C-bond homolysis to form a diradical. Computational studies by Gety, Hrovat, and Borden indicated that there would be a preference for

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• triene system, which is susceptible to cis–trans isomerization, have been longstanding problems in the area of inthomycins. The problems are more acute for the construction of enantioenriched β-hydroxycarbonyl units as evident from the recent reports [19][20][21]. Since the pioneering works of Henaff and

• )-(+)-54 to overcome the problems of isomerization of the (Z,E,E)-triene unit of the desired products. Finally, PdCl2(CH3CN)2 (1 mol %) in DMF was found to smoothly deliver the required triene (+)-55 in quantitative yield. After many unsuccessful attempts of direct conversion of methyl ester (+)-55 into

• . Stille coupling of (Z,Z)-(rac)-62 with vinyl iodide 48 in the presence of Pd(CH3CN)2Cl2 in DMF proceeded smoothly to give the corresponding ester (triene isomerization was less than 20% during coupling), which was then converted into acid derivative (rac)-63 by saponification. Finally, the acid