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

• of cytotoxic, antifungal, or antibiotic properties [10][11][12]. Modern stereoselective syntheses leading to highly substituted enamides include cross-coupling of vinyl (pseudo)halides or organoboron compounds [13], hydroamidation of alkynes [14][15][16], ynamide functionalization [17][18][19], or

• bond of vinyl (pseudo)halides during the Suzuki coupling have been published [25][26][27][28][29]. Typically, inversion of configuration occurs on substrates containing a double bond in conjugation with an electron-withdrawing group, such as the carbonyl group in enones [27][30]. We hypothesized that

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• acids have been shown to catalyze the reactions via single or double hydrogen bonding [57][58]. Saito et al. accomplished the chiral phosphoric acid-catalyzed intramolecular aza-Michael addition reaction of N-unprotected 2-aminophenyl vinyl ketones 90 to obtain chiral 2-substituted 2,3-dihydro-4

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

• found with Pd(OAc)2/bpy as the catalyst, N-methylacetamide as the solvent, and a temperature of 80 °C. Variously substituted indoles as well as esters of 118 (R = aryl, alkyl, vinyl) were generally well tolerated, but oxa- (X = O) and azo- (X = NR) cyclobutanes met with limited success. Alternative

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• . Common cryogel compositions include natural polymers such as gelatin and chitosan, and synthetic acrylamide-based polymers and poly(vinyl alcohol) (PVA) [12][13][14]. The reader is directed to a recent review by Thakor and co-workers which discusses cryogel synthesis in greater depth [15]. 2. Cryogel

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

• geometry was inferred from its NOESY spectrum, which showed a weak but distinct correlation between the vinyl proton singlet (δ 5.66) and the methylene group flanked by nitrogen and the ester (δ 4.06). The E-geometry was also suggested by the chemical shift of the hydrogen atoms at C-3 of the pyrrolidine

• the nucleophile to the carbonyl site, while in the latter case insertion of the vinyl unit between the carbonyl and the aryl ring makes the electrophilic site in the enaminone significantly less crowded. Cyclization of enaminones bearing heteroaromatic substituents proceeded very well (Table 2

• interaction between the vinyl hydrogen (δ 5.55) and the methylene unit adjacent to the ester (δ 3.96). The through-space anisotropic deshielding of C-3 in the ring (δ 3.32) by the carbonyl group also supported the assignment of the geometry. Microwave heating of intermediate 25a with silica gel in xylene

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• [Cu(dap)2Cl] and visible light are necessary for this transformation. In 2013, Ollivier and co-workers [45] successfully applied the same strategy to the allylation of diphenyliodonium 2. In 2017, Liu’s group [46] reported the copper salt-catalyzed cyclization of vinyl azides 3 with ammonium

• resulting cyanoalkyl radical then adds to the alkene to form a new alkyl radical. This radical is captured by a high-valent CuIII complex, which undergoes a reductive elimination to give the target product (Scheme 12). In 2018, Reiser and co-worker [63] established a CuII-catalyzed oxo-azidation of vinyl

• with oxime esters. Oxo-azidation of vinyl arenes. Azidation/difunctionalization of vinyl arenes. Photoinitiated copper-catalyzed Sonogashira reaction. Alkyne functionalization reactions. Alkynylation of dihydroquinoxalin-2-ones with terminal alkynes. Decarboxylative alkynylation of redox-active esters

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

• -annulation reaction may undergo a free-radical addition pathway. Firstly, NFSI oxidizes Cu(I) to form bissulfonylamidyl radical 10. Secondly, intermolecular nitrogen free-radical addition to the alkyne provides the vinyl radical 11. Then, there may be two possible pathways. Path a: vinyl radical 11 is

• trapped by Cu(II) to deliver the Cu(III) species 12, which undergoes intramolecular annulation and reductive elimination to afford the desired product 8 and regenerate the Cu(I) catalyst. Path b: vinyl radical intermediate 11 is oxidized by Cu(II) to give the cationic vinyl species 14. Finally, the

• ]. Then, they also reported another CuH-catalyzed coupling reaction of 1,3-enynes 54 and nitrile to prepare polysubstituted pyrroles 55 (Scheme 21) [66]. The substrates 54 could be easily prepared by Sonogashira coupling of terminal alkynes and vinyl halides. It is worth mentioning that the addition of

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• attractive strategy for the synthesis of carbazole derivatives [28][29][30][31][32][33][34][35][36][37][38][39][40]. In recent years, by using the one-pot domino synthetic strategy of in situ-generated 2-vinyl- or 3-vinylindolines and sequential Diels–Alder reaction with activated dienophiles, we have

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• bond of these oxadiazoles quantitatively resulted in E/Z-vinyl triflates. The reactions of the cationic intermediates have been studied by DFT calculations and the reaction mechanisms are discussed. Keywords: acetylene-oxadiazoles; Friedel–Crafts reaction; hydroarylation; superelectrophilic activation

• protonation of 5-acetylenyl-1,2,4-oxadiazoles 3 (Table 1), one would propose the following reaction pathways for compounds 3 in Brønsted superacids (Scheme 2). Protonation of oxadiazole 3 affords dication B, which may react with counter anion of acid X− giving rise to vinyl derivatives 4. In the presence of

• vinyl triflates 4a–c with a predominant formation of Z-isomers as product of an anti-addition of TfOH to the acetylene bond (Scheme 3). E/Z-Stereochemistry of compounds 4a–c was determined by H,F-NOESY correlation between vinyl proton (>C=CH–) and the CF3 group from the TfO substituent (see Supporting

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

• epoxide using vinyl Grignard reagent followed by esterification with acrylic acid (35) proved to be inefficient due to low reproducibility and poor isolation of product 36. The strategy was altered by changing the terminal epoxide 34 to an allylic alcohol (95%) utilizing dimethyl sulfonium methylide

• -promoted double bond migration. The cyclopropyl functionality in 46 can be assembled from the reaction of sulfur ylide and the α,β-unsaturated ketone 47, which in turn can be realized from the cross metathesis between commercially available ethyl vinyl ketone (48) and the C2-symmetrical diene-diol 49. The

• afforded in 78% yield as an (E)-isomer exclusively after reaction with excess ethyl vinyl ketone (48) in the presence of a catalytic amount of Grubbs II catalyst and CuI. The free secondary alcohol in 51 required a protection prior to the next transformation. For this purpose, MEMCl was chosen instead of

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• this protocol using the chiral iPrBiOx ligand under slightly modified reaction conditions (Scheme 19) [72]. Recently, Chu achieved the selective assembly of vinyl and aryl functionalities onto saturated cyclic hydrocarbons via a photoredox nickel-catalyzed sequential C–O decarboxylative vinylation

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• method using π-activated alcohols has frequently been used for xanthene synthesis. Some of these methods are the stereoselective synthesis of 9-vinyl-substituted unsymmetrical xanthenes and thioxanthenes by intramolecular FCA reaction [39], Lewis acid-catalyzed intramolecular FCA [40], and the synthesis

• synthesis is based on the o-quinone methide intermediate [54][55][56][57][58]. The carbocation formed by the activation of an alkene with acid turns into an intermediate o-quinone methide, resulting in a successful cyclization. As seen in the mechanism, the acid catalyst adds to the vinyl group, allowing

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• )vinyl)-3-cyano-5,5-dimethylfuran-2(5H)-ylidene)malononitrile in 65% yield. A second Claisen–Schmidt condensation of 2-(4-((E)-2-((E)-2-chloro-3-(ethoxymethylene)cyclohex-1-en-1-yl)vinyl)-3-cyano-5,5-dimethylfuran-2(5H)-ylidene)malononitrile with the appropriate 3-alkyl-1,1,2-trimethyl-1H-benzo[e]indol-3

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

• (transformation of the vinyl group at C-6 was preferred, except for the reactions of isoxazoline (±)-4 with 7f and 7g), while all CM reactions of (±)-6 were completely regioselective (the vinyl group at C-6 was transformed first). This can be explained by steric hindrance: the substituent at C-3 on the

• isoxazoline ring shields the vinyl group at C-4 from reacting with the bulky catalyst molecules (Figure 4). For the smaller Me or Et groups, this effect is relatively weak (only some reactions of (±)-5 with 7c and 7e were completely regioselective). The large Ph group, however, provided complete

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

• -handle, their fluorinating power was low. They could fluorinate only reactive carbanions, but not aromatics, olefins, vinyl acetates, trimethylsilyl or alkyl enol ethers, and so on. Soon after (1986), Schwartz and co-worker reported the stereospecific synthesis of alkenyl fluorides with N-fluoro-N-tert

• shows 31 examples and their methods of preparation. Umemoto and co-worker also reported the synthesis of a polymer version, poly(vinyl-N-fluoropyridinium salts) of these reagents [36]. The reactivities of many N-fluoropyridinium salts were examined [32] and mainly five kinds of N-fluoropyridinium salts

• , olefins, silyl enol ethers, vinyl acetates, sulfides and so on, under mild conditions with high selectivity and yields [29][30][31][32]. All these reactions could be carried out routinely using standard glassware in normal laboratory environments and without any specialist training. Some interesting

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

• , the difunctional divinyl sulfone was tested as the strongest Michael acceptor (E = −18.36, for phenyl vinyl sulfone [19]) under investigation. In distinction from the experiments described above, three equivalents of the alcohol were used. In general, the different catalysts perform very similar in

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• any Watson–Crick base pairing scheme, AOVP lowered the stability of PNA duplexes with complementary DNA and RNA [132]. Similarly, vinyl-modified purine (AVP) effectively crosslinked with thymine in DNA and with uracil in RNA. The crosslinking resulted in inhibition of Dicer processing of microRNA

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• ) [45]. In 2020, Ramachary et al. reported the 1,3-dipolar cycloaddition of various enones 43 and 46 with less reactive vinyl/alkyl/aryl azides 44 via an enolate-mediated organocatalyst. This protocol provides diverse double C- and N-vinylated 1,2,3-triazole derivatives and C-vinylated 1,2,3-triazole

• products. The tolylvinyl azide substituted with methyl at the ortho position afforded a lower yield of the desired product. The vinyl azides containing 2-naphthyl, β-phenyl, and 1-((2-azidoallyl)oxy)-4-nitrobenzenevinyl azides formed the corresponding products in high yield as well. Moreover, the alkyl

• -substituted cyclic enones treated successfully with azidophiles to give good yield of the corresponding double C- and N-vinylated 1,2,3-triazole derivatives 45. Then, the reaction was extended to some aryl and alkyl azides and different cyclic enones. Moreover, a variety of vinyl, alkyl, and aryl azides were

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

• sufficient. The reaction tolerated (hetero)aryl and aliphatic tosyl hydrazones as radical acceptors and a variety of olefins with different electronic natures as nucleophilic partners (i.e., vinyl ethers, sulfides, and acetamides). One example of the synthesis of a quaternary center was reported by the

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• -vinylphenyl)acetaldehyde (13a) using the route as outlined in Scheme 4. The synthesis started with the Wittig reaction of 2-bromobenzaldehyde (9a) with (methoxymethyl)triphenylphosphonium chloride (MTPPC) upon action with n-butyllithium in THF at 0 °C to give the vinyl ether 10a that was subjected to acidic

• vinyl aldehydes 13, next the cascade Prins/Friedel–Crafts reaction was examined. We started our investigations by applying aldehyde 13a as the model substrate (Scheme 5). A Lewis acid screening was carried out to identify the best catalyst for the tandem intramolecular Prins/Friedel–Crafts reaction

• of 2-(2-vinylphenyl)acetaldehyde (13a). Modified synthesis of 2-(2-vinylphenyl)acetaldehydes 13a–g and 1-vinyl-2-naphthaldehyde (13h). Lewis acid-catalyzed Prins/Friedel–Crafts reaction of 13a with veratrole. Use of different nucleophiles for the cascade reaction with 13a. Reaction conditions: a

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

• Tsutomu Kimura Koto Sekiguchi Akane Ando Aki Imafuji Department of Chemistry, Graduate School of Science, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan 10.3762/bjoc.17.94 Abstract A series of 1-heteroatom-substituted vinyl p-tolyl sulfoxides were prepared and

• rearrangement of magnesium alkylidene carbenoids 3 by using 13C-labeled sulfoxides and by using DFT calculations is also described. Results and Discussion Synthesis of 1-heteroatom-substituted vinyl p-tolyl sulfoxides As magnesium alkylidene carbenoid precursors, a series of 1-heteroatom-substituted vinyl p

• series of 1-heteroatom-substituted vinyl p-tolyl sulfoxides 2a, 5–7, and 1-unsubstituted sulfoxide 8 were treated with organometallic reagents with the aim of finding the optimal combination of the metal and heteroatom substituent for the FBW rearrangement (Table 1). The 2,2-bis(4-methoxyphenyl

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

• with InBr3 as Lewis acid, in dichloromethane at room temperature [106]. Under these reaction conditions, sulfinyl imine is formed first along with the boronate by interaction of the corresponding vinylboronic acid with the carboxylic group of the imino acid intermediate. The transfer of the vinyl unit

• to the electrophilic iminic carbon took place in a quite rigid system, with chelation of the Lewis acid with the nitrogen of the imine and carboxylate oxygen, forming a five-membered ring. The migration of the vinyl group occurred to the Re face of the imine, which is less shielded than the Si face

• products were obtained after four additional steps: cross-metathesis of allylated compounds 120 with methyl vinyl ketone, reduction of conjugated C=C double bond, removal of the sulfinyl group under acidic conditions, and final stereoselective reduction of the imine formed by intramolecular cyclization

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

• trifluoromethylation (Scheme 25). A variety of olefins, such as ene carbamates, styrene, aliphatic olefins, vinyl ethers, and acrylates are compatible in this approach, affording corresponding β-(trifluoromethyl)alkynes with good to excellent yield. The bifunctionalization was achieved by an EDA-complex-initiated