Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• structures using 1H NMR spectroscopy (Scheme 3). Larger values of 3JH6-F were observed for the exo-F isomers. The presence of a strong EWG on the aryl substituent led to higher stereoselectivity. For example, approximately a 2:1 ratio was observed for the nitro- and carboxymethyl-substituted products 3b, 3c

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

• (Scheme 23) [64]. Fürstner et al. [67] showed that (trifluoromethyl)gold(I)triphenylphosphine in dichloromethane can be used for the production of difluorocyclopropanes at low temperatures. The advantage of the method is its stereoselectivity. The disadvantages include the stoichiometric use of gold, low

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• the light of Woerpel’s model, which characterizes the direction of nucleophilic addition to oxocarbenium ions [41][42][43]. According to this concept, the conformational stability of the compound in question is the key property to consider when predicting the reaction’s stereoselectivity. When the

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• , it was transformed into (E)-vinylboronate (+)-145b in perfect stereoselectivity by using the recently developed boron-Wittig reaction with bis[(pinacolato)boryl]methane (144) [79]. By applying the Corey–Fuchs dibromoolefination and followed by Pd-catalyzed hydrogenolysis under Uenishi's conditions

• [80], compound (Z)-(+)-143a delivered the bromodiene (Z,Z)-(+)-145a in good yield and stereoselectivity. Isomerization of (Z)-(+)-143a to (E)-(+)-143b was carried out successfully using sterically hindered base DBU or DABCO. Treatment of (E)-(+)-143b with 144 using the boron-Wittig reaction [79

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• hydrogenation occurred with high stereoselectivity producing a single diastereoisomer of 29. Then, the amide was treated with methyllithium at −78 °C to provide ketone 30 in 85% yield. Subsequently, the intramolecular Mannich reaction was carried out, leading to the desired alkaloid, via precursor 32. Ketone 30

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• vinylphosphonates from simple and commercially available alkynes proceeds under mild conditions with high stereoselectivity, and thus enabling the rapid construction of molecular complexity. Results and Discussion We investigated the reaction of phenylacetylene (1a), Selectfluor®, and diethyl phosphite to afford β

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• moieties (the alkyl group on the calixarene and the chiral centre on the urea moiety) function synergistically, and a proper choice of both substituents can lead to an even better stereoselectivity. Conclusion In conclusion, the introduction of chiral alkyl groups into the lower rim of calix[4]arene

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• various deoxyfluorination reaction conditions. In our specific case, we were able to modulate the stereoselectivity of the nucleophilic fluorination at C4 with the use of Et3N·3HF. As proposed by the group of Linclau [20], we support the involvement of an oxiranium intermediate (results reinforced by

• deoxyfluorination is a difficult task to achieve. The simple synthetic approach described herein and the use of Et3N·3HF as an alternative to the unpredictable DAST looked promising. In the specific case of triflate 13, we were able to modulate the stereoselectivity of the nucleophilic fluorination at C4 using

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• )-15b were formed as single products, without any regio- or stereoselectivity issues (Scheme 8). However, repeated N-halosuccinimide addition was necessary, and the yield of the bromofluorination reaction was still mediocre. The stereochemistry of the products (rac)-15a and (rac)-15b was determined by

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• David Van Craen Jenny Begall Johannes Grosskurth Leonard Himmel Oliver Linnenberg Elisabeth Isaak Markus Albrecht Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.16.195 Abstract The stereoselectivity of a Diels–Alder reaction within the

• on the results of the stoichiometric reaction, a secondary amine-catalyzed nitro-Michael reaction is performed as well which afforded reasonable diastereoselectivities. Keywords: Diels–Alder reaction; enamine catalysis; hierarchical helicates; remote-control; stereoselectivity; Introduction Carbon

• –carbon (C–C) bond-forming reactions play a key role in organic chemistry. Hereby the stereoselectivity of the reaction is highly important due to the different behavior of stereoisomers in human metabolism [1][2]. Stereocontrol was achieved either via an auxiliary [3][4][5][6][7] or a catalyst [8], both

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• pyrrolidine byproduct. Using the Stork–Zhao conditions [23], the Nicolaou group performed an α-methyliodomethylenation of 24 to give 33 with a good stereoselectivity (Z:E ≈ 95:5, Scheme 4) [24][25]. After the hydrolysis of the dimethylaminal and the reaction of the resultant amine with phthalic anhydride, a

• with a poor stereoselectivity, however, a similar reduction of the diethyl acetal of 38, followed by an acetal hydrolysis gave the aldehyde 39 with a good stereocontrol (>10:1). It is not possible to make a direct comparison of the efficiency of these three routes as they do not lead to an identical

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• improvement allowing to obtain 12a with up to 73% ee through the reaction with dihydroquinine benzyl ether (DHQ-Bn, Table 3, entry 12). Switching to quinidine (QD), dihydroquinidine (DHQD), and their derivatives allowed to alter the stereoselectivity of the process leading to the preferred formation of

• fluorinations with QD and DHQD led to the reversed stereoselectivity as compared to the reactions with Q and DHQ. For the benzylamine-derived substrates 8a–c benzyl ether derivatives of cinchona alkaloids favored the formation of the same enantiomer of 12 as their free alcohol counterparts (e.g., both Q-Bn and

Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups

• Xiaoyun Hu,
• Jianxin Guo,
• Cui Wang,
• Rui Zhang and
• Victor Borovkov

Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155

• indicated that the two free hydroxy groups in phosphoric acid 3 played a pivotal role in improving the stereoselectivity. A plausible activation model and reaction pathways of the stereogenic step in the phosphoric acid 3-catalyzed Biginelli-like reaction was proposed. This promising result prompted us to

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• -aldol reaction affording the final product (Scheme 34). This mechanism was experimentally supported by the beneficial effect of water and the observation of HF-loss by 19F NMR. The catalytic version of this process was also studied. The best results in terms of efficiency and stereoselectivity were

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• reactivity of 2-vinylpyrroles substituted by electron-withdrawing groups [34][35]. Interestingly, all the 2-vinylpyrroles, including the N-unsubstituted 16a,b or the N-substituted ones 8a and 8c–j, furnished a high endo stereoselectivity with dienophile 7c, except the N-substituted 2-acrylonitrile pyrrole 8b

• endo selectivity in the Diels–Alder cycloadditions. Since experimental and theoretical results have demonstrated that the nature of the C–H···π interaction mainly depends on the dispersion interactions [64][67][77], these are probably not only at the origin of the endo stereoselectivity of the present

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• isoxazolidines by means of dihydroxylation [9][10] and epoxidation [11][12] reactions. Regarding the stereochemistry, almost all of the realized additions proceed with an excellent trans stereoselectivity relative to the substituent at C-3, giving isoxazolidine-4,5-diols and isoxazolidinyl epoxides with a C-3/4

• the intended stereoselective reduction of cyclic ketones with the aim to obtain the 4-hydroxyisoxazolidines with a relative C-3/4-cis configuration. Whereas the initial attempts of the reduction of 9a with lithium borohydride resulted in a poor stereoselectivity (70:30 in favor of the desired cis

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• ]. Photodecarboxylations were also intensively investigated in a series of nonsteroidal anti-inflammatory drugs [22][23][24] such as ketoprofen [25][26][27][28][29][30][31][32][33][34], due to photoallergic responses initiated by photodecarboxylation of these drugs [35]. Stereoselectivity in photochemical reactions can be

• achieved by use of supramolecular chemistry [36][37]. For example, stereoselectivity has been reported for photochemical reactions taking place in the inclusion complexes with CD [38][39][40][41] or structurally modified CDs [42][43][44][45][46][47]. Since β-CD is often used in pharmaceutical applications

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• the five-membered ring occurred regioselectively and the expected tetrahydrothiophene-3,3-carboxylates were the products. The studied reactions displayed an interesting stereoselectivity and, in the case of 2,5-diaryl-substituted products 9, both aryl groups were exclusively located at the opposite

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• endocyclic, high stereoselectivity was observed with the formation of trans-products (examples 106c and 108b). The oxidative cyclization of β,γ-unsaturated oximes 109 under the action of molecular oxygen and catalytic amounts of bis(5,5-dimethyl-1-(4-methylpiperazin-1-yl)hexane-1,2,4-trione)cobalt(II) (Co

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• establishes the syn approach of the C=C bonds. As a result, only the ε-isomer can be obtained and the stereoselectivity of the method is complete. As discussed previously, photocycloaddition products from the [2 + 2] reaction of the cisoid isomers of 3 were not observed, and we are unaware of the reasons for

• findings were also confirmed by analysis of the 13C NMR spectra. Conclusion The synthesis of cyclobutane 1,3-diaminotruxillic bis-amino acids has been achieved with full stereoselectivity (ε-isomer) starting from polyfunctional oxazolones 2 derived from the chromophore of the Kaede protein in three steps

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• presence of Pd(OAc)2 as a catalyst. The corresponding β-fluoro derivatives 159a–v were obtained with high stereoselectivity using DCM and iPrCN as co-solvent (30:1 v/v). Interestingly reducing the Pd(OAc)2 concentration from 10 mol % to 6 mol % led to an improved yield of 73% for 159a, 159g, and 159t

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• (Scheme 3 (c)) leads to the expected 1,3-diene (Scheme 3 (d–f)). A particular advantage of the enyne metathesis is that the stereoselectivity can be readily controlled by the intramolecular vs the intermolecular process. Among the vast array of bioactive organic molecules already synthesized through enyne

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• plays crucial roles in both the catalytic activity and stereoselectivity [19][20][21]. Notably, these catalyst systems were also applicable for three-component coupling reactions using hydrosilanes as hydride reagents [17]. Based on this knowledge, we decided to investigate the effects of the phenol–NHC

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• stereoselectivity (Scheme 1, this work). Similarly, Zhu’s group has reported that the reaction of an alkyne and an α-bromocarbonyl compound furnishes a highly functionalized 1,3-enyne compound via ATRA followed by an alkynylation reaction [22], but both Pd and Cu are required as catalysts in that case. Our

• with good regio- and stereoselectivity. Results and Discussion In our preliminary research, we tried various Cu salts, including CuI, CuBr, CuCl, CuOAc, and CuOTf, and ligands, including PPh3, 1,10-phenanthroline (1,10-Phen), N,N,N',N'',N''-pentamethyldiethylenetriamine, and tris(2-pyridylmethyl)amine

• , in the reaction of phenylacetylene (1a) and α-bromoester 2a. From these experiments, CuBr and 1,10-Phen acted as a good catalyst system for obtaining 1,3-enyne 3a in 62% yield with good regio- and stereoselectivity (Table 1, entry 1). On the basis of this preliminary result, we also tried other

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• , providing a simplistic access to open-shell intermediates. These two synchronizing and rapidly flourishing areas of research in modern synthetic chemistry have recently been merged, and their association was found to be very effective in terms of chemo-, regio-, and stereoselectivity aspects. Therefore, we