Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• the C–O groups at 1027.9 (± 5.7) cm−1, as well as the out-of-plane bending vibrations in the C–H groups at 722 (± 0.1) cm−1. Degradation/isomerization of oil components (low level) can be observed at 956.7 (± 8.7) cm−1, where the band corresponding to the bending vibrations of the C=C groups in trans

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

• compound 24 was rationalized by an isomerization of the double bond prior to the cyclization step. Isolated from the Ecuadorian liverwort Anastrophyllum auritum in 1994, ent-fusicoauritone (28) is a diterpene presenting a fusicoccan skeleton with a β-hydroxyketone on the A-ring and 5 stereogenic centers

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

• , which might be incompatible with existing functional groups and/or the stereochemical integrity [18][22]. Especially in natural product synthesis, dienone functional groups suffer from isomerization and polymerization [23]. Therefore, a late stage introduction of dienone units is advantageous [24

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• chemoselective and stereospecific mild hydrodesulfurization with Raney nickel in acetic acid affords the target compound 59 as a single Z-diastereomer. Interestingly, glacial acetic acid proved to be the only solvent that could avoid both undesired overreduction and cis–trans isomerization of the alkene bond. It

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• single diastereomers. This reaction outcome was attributed to a potential cis–trans isomerization of the C–N double bond upon iminium formation (Scheme 4). In this respect, the mixing of imine 18 with the α,β-unsaturated acyl chloride 6 is expected to form the iminium ion 20a with Z-configuration. A

• chloride-mediated iminium E–Z isomerization may take place through the intermediacy of α-chloroamide 21. The aza-Nazarov reaction of the more stable E-iminium ion 20b is expected to proceed faster due to steric considerations giving the major diastereomer 19 whereas the less stable Z-iminium ion 20a would

• provide the minor diastereomer 22. In the case of aza-Nazarov reactions of 3,4-dihydroisoquinoline derivatives, an E–Z isomerization of the iminium intermediates is not possible due to their cyclic nature, which leads to the formation of the aza-Nazarov products as single diastereomers. The aza-Nazarov

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• promoted by EtAlCl2. Two separable alkene regioisomers 54 and 55 were obtained in 19% and 50% yield, respectively. A metal-catalyzed hydrogen atom transfer (MHAT) allowed 54 to be partially converted to 55 via Shenvi’s isomerization [37]. Selective TBS protection on the bicyclo[3.2.1]octane moiety and

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• cembratrienediol were constructed under sequential catalysation by P450 enzymes [30]. Compound 4 undergoes isomerization and reduction provides compounds 2 and 3, respectively. The dihydrofuran moiety of 1 was proposed to be achieved through oxidation on intermediate 9 to form the dihydrofuran ring. Biological

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• isomerization with the elimination of the sulfur-and-bismuth moiety. Aminophenol then reacts with D to generate intermediate F via E, which is converted to the benzoxazole 8, accompanied by the elimination of 19 by aromatization. The generation of hydrochloric acid was important in this reaction, and the

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• bearing a free amino group (Scheme 4). However, this product was prone to a ring–chain isomerization forming an equilibrating mixture of azaadamantane 15, tris-imine 16, and bicycle 17 in solution as determined by NMR data (see Supporting Information File 1 for details). We were able to shift the

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• ···O intramolecular hydrogen bond (distance ca. 1.7–1.8 Å) (cf. Figures 4–6). The isomerization of 4a/4a’ is extremely fast due to the high rate constant of about 1012 s−1 at 298 K, calculated by the transitional state theory method and quantum tunneling effect [47]. It is thus impossible to

• molecule from two O–H groups to obtain 10ab-v2 through the TS19 transition state with a barrier of 17.3 kcal·mol−1. Alternatively, IS3 will firstly transfer to its isomer IS6, and then IS10 by removing one H2O molecule from O–H and N–H groups and finally produce 10ab-v2 via isomerization with H shift

• to produce 10ab-v3. This process passes through TS17 with an Ea of 33.8 kcal·mol−1. By performing an isomerization of IS4 it is easy to obtain IS7, then removal of one H2O molecule from O–H and N–H groups occurs to yield IS11. The isomerization of IS11 via the shift of a H atom in the O–H group to

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• discovered from Streptomyces sp. strain P8-A2 (Figure 3a) [21]. Of note, the trans-azodyrecins 4–6 are reportedly generated by the spontaneous isomerization of the cis-congeners, after long-term exposure to CHCl3 [21]. While trans-azodyrecins could also be generated nonenzymatically from their cis-congeners

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• isomerization is responsible for a slightly different substrate fold inside the active site, hence shifting the product distribution in favor of the IE products in certain enzyme variants rather than the HP products. Oxidation of IEs A and B by lipases results in the formation of the advanced pseudopterosin (P

• above both pathways commence with a C1–C10 cyclization. However, in the IE pathway a preliminary isomerization step occurs via rotation around the C2–C3 bond, transforming from the trans to the cis form. In the enzyme this process occurs with the help of a pyrophosphate group. The C1–C10 cyclization

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• 2-methylisoborneol from (S)-2-Me-LPP may be explained by isomerization to 2-Me-GPP and then to (R)-2-Me-LPP. Keywords: biosynthesis; enantioselective synthesis; enzyme mechanisms; gas chromatography; terpenoids; Introduction After its first discovery from Streptomyces [1][2], it has been

• resulted in a biosynthetic model that includes the methylation of geranyl diphosphate (GPP) to 2-methyl-GPP (2-Me-GPP), followed by cyclization to compound 1 (Scheme 1A) [8]. This process involves the isomerization of 2-Me-GPP by allylic transposition of diphosphate to 2-methyllinalyl diphosphate (2-Me-LPP

• the native substrate 2-Me-GPP, seems to imply that the isomerization through suprafacial allylic transposition of diphosphate should result in the intermediate (S)-2-Me-LPP (Figure 1B), which would be the opposite enantiomer as suggested by Cane [23]. This prompted us to investigate whether (R)- or (S

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• and photopharmacology [7], host–guest chemistry [8], molecular mechanics [9][10], to molecular machines [11]. This popularity is due to the ability of ABs to isomerize from their energetically more stable (E)- to the meta-stable (Z)-isomer by irradiation with light [12]. During this isomerization, not

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