A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• multiple stereogenic centers. The synthesis involved selective cycloadditions, with subsequent ROM of the formed cycloalkene-fused isoxazoline scaffolds and selective CM by chemodifferentiation of the olefin bonds of the resulting alkenylated derivatives. Various experimental conditions were applied for

• the CM transformations with the goal of exploring substrate and steric effects, catalyst influence and chemodifferentiation of the olefin bonds furnishing the corresponding functionalized, fluorine-containing isoxazoline derivatives. Keywords: functionalization; metathesis; nitrile oxide

• ; organofluorine chemistry; selectivity; Introduction Olefin metathesis is considered to be a powerful synthetic tool for the creation of olefin bonds [1]. Several types of metathesis reactions, such as ring-opening metathesis (ROM), cross-metathesis (CM), ring-closing metathesis (RCM) or ring-opening/cross

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

• sequential modifications [30], photocyclization of divinylterphenyl derivatives [31], tandem radical cyclization of (Z,Z)-1,4-bis(2-iodostyryl)benzene derivatives [32], and ring-closing olefin metathesis of tetravinylterphenyls [33] as the best-known synthetic routes. Herein, we have classified the synthetic

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• cyclic peptide motif (Scheme 11). Dipeptide substrate 26f decorated with a Morita–Baylis–Hillman carbonate underwent the intramolecular C–H allylation process to yield cyclic peptide 28f under dilute reaction conditions. This macrocyclization strategy introduces an exocyclic olefin motif onto the cyclic

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• to an activated electrophile, e.g., an electron-deficient olefin, generating a zwitterion (i, Scheme 1). In further course, the zwitterion acts as a nucleophile or as a base [1]. The efficiency of the formation of this β-phosphonium α-carbanionic species depends on the nucleophilicity of the

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

• Thiago S. Silva Fernando Coelho Laboratory of Synthesis of Natural Products and Drugs, Department of Organic Chemistry, Chemistry Institute, University of Campinas, PO Box 6154 - 13083-970, Campinas – SP, Brazil 10.3762/bjoc.17.112 Abstract Olefin double-bond functionalization has been

• , numerous hydroalkylation methodologies have emerged that have explored the diverse reactivity patterns of the olefin double bond. This review presents examples of olefins acting as electrophilic partners when coordinated with electrophilic transition-metal complexes or, in more recent approaches, when used

• expense of the olefin double bond. Review Olefin activation by transition metals Transition metals can act as π-acid catalysts in olefin double bond activation, as they weaken the alkene double bond through coordination to allow a nucleophilic attack on the sp2 carbon to form an alkylmetal intermediate

Analogs of the carotane antibiotic fulvoferruginin from submerged cultures of a Thai Marasmius sp.

• Birthe Sandargo,
• Leon Kaysan,
• Rémy B. Teponno,
• Christian Richter,
• Benjarong Thongbai,
• Frank Surup and
• Marc Stadler

Beilstein J. Org. Chem. 2021, 17, 1385–1391, doi:10.3762/bjoc.17.97

• structure resembling that of the carotane sesquiterpenoid fulvoferruginin (1, [8]) with the only difference being a tertiary methyl group at C-14 (δC/H 8.7/1.20), instead of an olefin. Compound 2 was therefore named fulvoferruginin B. Subsequently, a minor peak following 2 in the HPLC chromatogram was

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

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

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• Scheme 49. Unlike allyl- and vinylsilanes, as discussed earlier, Furman and co-workers introduced a new concept of synthesizing 211 utilizing silyl-Prins cyclization of propargylsilane 209 and aldehyde 210 in the presence of TMSOTf [93]. The oxocarbenium ion was intramolecularly trapped by the olefin

• mechanism similar to simple Prins cyclization, except trapping of oxocarbenium ion 214 with silyl enol ether instead of olefin, vinylsilane, or allylsilanes, was proposed as shown in Scheme 51. However, the reaction of silyl enol ether such as 216, upon reacting with an unsaturated aldehyde 217, produced a

• a (Z)-olefin. The addition of ZnCl2·Et2O and (MeO)3CH to the resulting homoallylic alcohol 247 leads to the desired pyran derivative 248, having an acetal group at the C2 position (Scheme 58). By treatment of acetal 248 with allyltrimethylsilane gave 2,6-anti-configured THP 249 as a single

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

• complex based on previous work in 2017 [21]. The reaction is initiated by the formation of EDA complex between electron acceptor N-acyloxyphthalimide 90 and electron donor HE 79, completing regio- and chemoselective C(sp3)–H allylation or olefin bifunctionalization (Scheme 31). In 2018, Tang and Studer

• yielded by addition of perfluoroalkyl radical with olefin 96 (Scheme 34). Upon the termination of the reaction, the desired product can be given by removing the solvent and precipitating the catalyst. The comparison experiments and electronic absorption spectra showed that the efficiency of the catalyst

• the secondary amine catalyst (Scheme 39). In 2019, Kappe and colleagues [36] reported a method to complete perfluoroalkylation of olefins under visible light in flow. Perfluoroalkylated olefin 118 was prepared by employing olefin 116 and perfluoroalkyl iodides 117 as substrates as well as

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

• 9m,n with cyclopent-1-en-1-ylmethyl or cyclohex-1-en-1-ylmethyl substituents on nitrogen similarly cyclize via envelope transition states trans-21m,n and cis-21m,n with preferred trans orientation of the olefin unit and the silyloxy-bearing side chain (Scheme 10). Thus, similarly as for 12a–k, two

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• materials and it could be recovered and reused maintaining its unaltered high activity. Keywords: alkenes; cobalt nanoparticles; epoxides; oxidation; TBHP; Introduction Olefin oxidation reactions are key synthetic transformations in the production of oxygenated chemicals of high interest for both academic

• and industrial applications [1]. Among them, allylic oxidation and olefin epoxidation constitute fundamental tools for the synthesis of homoallylic alcohols or α,β-unsaturated carbonyl compounds, and epoxides, respectively. In particular, epoxides are pivotal building blocks for the synthetic chemists

• greener oxidizing agents as molecular oxygen, hydrogen peroxide or tert-butyl hydroperoxide (TBHP) [14][15][16][17]. However, using any of these oxidants alone results in considerable low reactivity and selectivity in olefin epoxidation reactions. Thus, several transition-metal-based catalytic methods

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• reactions (Scheme 1a). Diels–Alder (Scheme 1b) [15] and radical reactions (Scheme 1c) [16] directed toward helicene synthesis require high temperature conditions even for low to moderate yields. Olefin metathesis (Scheme 1d) [17] and alkyne trimerization (Scheme 1e) [18][19] require the use of expensive

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

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• formal synthesis of inthomycin C ((−)-3). In 2018, Donohoe et al. demonstrated a tin-free, short and efficient total synthesis of inthomycin C ((−)-3) by comprising the three key steps of C−C bond-forming reactions: i) a vinylogous Mukaiyama aldol reaction, ii) an olefin cross-metathesis reaction, and

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

• , activated by lithium ion in a tricyclic N,O-acetal (−)-46, and an olefin metathesis (RCM) of a dialkenylpiperidine (−)-50 for the construction of an azabicyclononane system [48]. The synthetic sequence described by the authors is shown in Scheme 6. The lactam present in 43 was opened by treatment with

• before the key cyclization step. It was also the first example of olefin metathesis in (−)-adaline (1) synthesis. Kibayashi's approach consisted of 13 steps in an overall yield of about 28.3% from precursor 43, previously used by the authors in the synthesis of (−)-adalinine [49]. The spectral data (1H

• , Spino et al. firstly made the quaternary center, followed by cyclization. Furthermore, Spino's synthesis involved key reactions such as Claisen rearrangement, olefin metathesis, and the Curtius rearrangement that allowed both natural products in good yields. Davis synthesis – 2010 Davis and Edupuganti

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

• ] cycloaddition through diyl trapping with an olefin [14][15] and Trost’s palladium-catalyzed trimethylenemethane cycloaddition [16], which allows the preparation of five-membered carbocycles, have been emerged since the 1970s. Thereafter, many novel and important all-carbon [3 + 2] cycloaddition reactions, such

• cycloaddition adduct (not shown) [39] (Scheme 4B). Subsequent treatement with t-BuOLi resulted in the isomerization of the exo-olefin followed by exposure to n-butyllithium and Davis‘ oxaziridine 76 to give 77 in 60% yield with 89% ee. A three-step synthesis from 77 gave α,β-unsaturated amide 78, which

Activation of pentafluoropropane isomers at a nanoscopic aluminum chlorofluoride: hydrodefluorination versus dehydrofluorination

• Maëva-Charlotte Kervarec,
• Thomas Braun,
• Mike Ahrens and
• Erhard Kemnitz

Beilstein J. Org. Chem. 2020, 16, 2623–2635, doi:10.3762/bjoc.16.213

• surface of ACF can occur, generating carbenium-like species and surface fluorides (Scheme 3). Via HF elimination, the olefin 1 can be produced, followed by a refluorination of the double bond by the released HF, generating 10b (Scheme 3, left). In the presence of C6D6, the hydroarylation product 12 can be

• ratio between the olefin 1 and the refluorination product 10b observed in the presence of HSiEt3 was 3:1, whereas, without the silane, a ratio of 1:2 was detected. This difference in the ratio might relate to the amount of HF present in the reaction mixture, which would be lower in the presence of

• silane because the latter can convert with HF into fluorosilane and H2 [39][50][53]. Consequently, less refluorination takes place, and a higher selectivity towards the formation of the olefin 1 is observed. In C6D6, the activation of 10a gave comparable results as when no HSiEt3 was introduced (Scheme 4

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

• cyclic olefins, such as diesters, imides, and lactams with varied functionalization patterns and different structural architectures is described. The synthetic methodologies were based on electrophilic activation through halonium ions of the ring olefin bonds, followed by nucleophilic fluorination with

• mind, further plans concerning compound (rac)-13 were abandoned. We continued our studies with strained, rigid bicyclic systems. First, the N-Boc-protected Vince lactam (rac)-14 was subjected to halofluorination reactions. Despite the asymmetric nature of the olefin, the compounds (rac)-15a and (rac

• iodofluorination at reflux afforded only unreacted starting material. Since iodofluorination is usually more efficient than bromofluorination [19], the decreased yield of (rac)-20b compared to that of (rac)-20a is possibly caused by steric hindrance around the olefin bond, which affects the electrophilic attack of

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• [13][17][18][19][20]. The first-generation TLC approach for the synthesis of molecular knots involved a single knot precursor compound that had two macrocycles and two long tails [13][21]. Solvophobic effects [22][23] were used to promote the tail threading step, ring-closing olefin metathesis (RCM

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• % yield. Next, the methyl substituents were introduced at the position of the carbonyl groups of 23 to generate the methyl-substituted olefin derivative 25 via alkenyl phosphates 24 by means of three-fold cross-coupling reaction with methylmagnesium iodide in THF. Finally, during the tandem ROM–RCM, they

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• which point an olefination with the Tebbe reagent and the addition of methanol afforded the cyclic ketal as a separable mixture of the diastereomers 68 and 69 (≈4.5:1 ratio). The desilylation of 68 gave the 2° alcohol, which after oxidation and Tebbe olefination afforded the exocyclic olefin 70. The

• exocyclic epoxide prior to the formation of the C-6–C-9 conjugated diene was necessary in order to avoid the unwanted epoxidation of the C-6–C-7 olefin. Koide employed a unique strategy in which the exocyclic epoxide was generated as the initial stereocenter (Scheme 15) [12][13]. The Sharpless asymmetric

• iodine-catalyzed Mukiyama–Michael addition of the ketene silyl acetal 104 to 103 afforded the trans-1,5-disubstituted tetrahydropyranone 105. After the generation of the C-3-exocyclic olefin and functional group manipulation, the Takai olefination [40] of the aldehyde 106 gave the trans-vinyl iodide 107

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• aromatic coupling partner, including frequently used Weinreb amides or functionalized secondary and primary amides. Regarding the scope of olefin substrates, the reaction tolerated numerous functional groups including acrylates, vinyl silanes or sulfones which was interesting from the post

• towards various functional groups such as aldehydes, ketones, and esters. Of note is that in some cases, partial hydrogenation of the double bond was observed, resulting probably from the generation of a ruthenium–hydride complex. However, this consecutive reactivity and the ratio between the olefin and