Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• University of Technology, Stremayrgasse 9, 8010 Graz, Austria 10.3762/bjoc.20.6 Abstract The reactions of 2,4-di-tert-butyl-6-(diphenylphosphino)phenol and various Michael acceptors (acrylonitrile, acrylamide, methyl vinyl ketone, several acrylates, methyl vinyl sulfone) yield the respective phosphonium

• and exhibit a negative solvatochromism. An analysis of the kinetics of the zwitterion formation was performed for three Michael acceptors (acrylonitrile, methyl acrylate, and acrylamide) in two different solvents (chloroform and methanol). The results revealed the proton transfer step necessary to

• %) of the adducts is in the range of 20.9–18.9 ppm. Only the acrylamide-derived phosphonium phenolate 2b is an exception, showing a 31P NMR shift of 25.1 ppm. The 31P NMR signal of 2,4-di-tert-butyl-6-(triphenylphosphonium)phenolate appears at 19.6 ppm [30]. Surprisingly, the 31P NMR shifts of the

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• and 401 nt long synthetic ssODNs, and functional in biological systems. Discussion For ODN purification using CBP, one major concern has been the damage of the ODN under the radical acrylamide polymerization conditions. Although some work has been done to prove that this is unlikely [22][23][24][25

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• acrylamides bearing a disubstituted arene (29g,h) and an heteroaryl (29i) at the α-position were also suitable substrates for this reaction. Finally, acrylamides bearing a methyl group at the α-position (29j) or the α,β-dimethylated acrylamide (29k) were suitable substrates albeit the corresponding products

• reaction was also tolerant to a large class of functional groups (halogens, cyano, trifluoromethyl), affording products 34c,d and 34e in high yields (86%, 89% and 81%, respectively). The α-methyl-substituted acrylamide 33j also underwent difluoromethylthiolation to give product 34j in 81% isolated yield

• acrylamide derivatives [140]. Using the same directing group, a panel of α-arylacrylamide derivatives 39a–f was successfully functionalized with a high Z-selectivity (yields up to 98%, Scheme 18). Both, thermal reaction conditions (DMSO at 70 °C for 16 h) and microwave irradiation (100 °C using microwaves in

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• Discussion Key elements of reaction optimization are summarized in Table 1. With NaI (20 mol %) and PPh3 (20 mol %), acrylamide 1a and redox-active ester 2a were used as model substrates to react for 36 h in acetonitrile (MeCN) under blue LEDs irradiation and N2 atmosphere, delivering the desired oxindole

• , good yields of the corresponding oxindoles (3da–ga) were achieved. A trifluoromethyl-substituted acrylamide afforded the product 3fa in very high 85% yield. In addition, ortho-substitution at the N-aryl moiety was also well tolerated, albeit with slightly decreased yields (3ha–ka, 50–63

• synthesis of (±)-physovenine and (±)-physostigmine alkyl analogues exhibiting inhibitory activity against acetylcholinesterase and butyrylcholinesterase [30][78][79][80][81][82][83][84]. Subsequently, we expanded the scope of this protocol to include a benzamide derived acrylamide 1r. The expected six

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

• , including kinetic isotope effects and radical trapping, suggested a radical mechanism. The hydroperoxide, in the presence of an iron catalyst, abstracts the hydrogen atom alpha to the heteroatom. The alkyl radical may attack the acrylamide; subsequent intramolecular radical cyclization with the aryl ring

• reaction begins with a radical addition to the acrylamide 60 followed by subsequent radical cyclization with the aryl ring. A few substituent effects were noted, namely ortho-substituents on the aryl ring were detrimental to the reaction. Moreover, terminal alkenes preformed poorer than their 1,1

• of functional groups with neither EDGs nor EWGs altering the reactivity of the acrylamide. Once synthesized, the authors demonstrated the oxindoles could be transformed into fused indoline–heterocycle frameworks in good yield, an attractive scaffold found in many biologically active compounds [119

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

• accelerated freezing rate or reduction in cryogelation temperature will lead to smaller pore sizes throughout the cryogel. This is because the solvent freezes at a faster rate, allowing only a small amount of crystal growth [13][14]. Ivanov et al. researched the production of poly(acrylamide) (PAAm) cryogels

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

• . Interestingly, the individual monomers usually do not exhibit responsive properties. However, the combination within a copolymer leads to a pronounced thermoresponse. A prominent representative of such behavior is poly(acrylamide-co-acrylonitrile), which is assembled from a fully soluble, hydrophilic monomer

• continuous development and improvement of polymerization techniques, more and more diverse copolymers can be synthesized. Very recently, Kertsomboon et al. succeeded in preparing a copolymer (poly(AAm-co-MDO)) of acrylamide and a degradable, hydrophobic monomer based on a ring opening polymerisation of

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

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

• and at room temperature. The results reveal a decisive superiority of TMTPP for converting poor and intermediate Michael acceptors such as acrylamide and acrylonitrile and for converting less acidic alcohols like isopropanol. With stronger Michael acceptors and more acidic alcohols, the impact of the

• triarylphosphines TPP, MMTPP and TMTPP as catalysts for the oxa-Michael reaction three varyingly strong Michael acceptors, namely acrylonitrile (1), acrylamide (2) and divinyl sulfone (3) were reacted with four different alcohols of similar molecular mass but different acidity (Figure 1). The stoichiometry of

• than those presented here can be achieved [22][23]. Switching to the weaker Michael acceptor acrylamide (E = −23.54 for N,N-dimethylacrylamide) [19], no useful conversions on any account were obtained. However, TMTPP performs best, giving 61 and 74% conversions with 1-propanol (b) and allyl alcohol (c

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

• reacted with electron-deficient alkenes (Giese-type addition) to form new C–C bonds in intra- and intermolecular fashions. The authors reported a great diversity of electron-deficient alkenes, including α,β-unsaturated carbonyl compounds like the usually less reactive acrylamide derivative 48c

Photoinduced post-modification of graphitic carbon nitride-embedded hydrogels: synthesis of 'hydrophobic hydrogels' and pore substructuring

• Cansu Esen and
• Baris Kumru

Beilstein J. Org. Chem. 2021, 17, 1323–1334, doi:10.3762/bjoc.17.92

• . Experimental Materials: 4-Methyl-5-vinylthiazole (vTA, 97%, Sigma-Aldrich), ʟ-(+)-ascorbic acid (AsA, 98+%, Alfa Aesar), N,N-dimethylacrylamide (99.0+%, TCI), N,N′-methylenebis(acrylamide) (MBA, 99%, Sigma-Aldrich ), acrylic acid (AA, 99%, Sigma-Aldrich), acrylamide (AAM, 98.5%, Acros), albumin–fluorescein

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• cyanomethylarylation of N-aryl/benzoyl acrylamide or allylamine involving the key C–H functionalization of readily available acetonitrile is a straightforward and powerful method to access these useful structures [13][14][15][16][17]. Over the last decade, although numerous protocols have been disclosed for the direct

• independently disclosed a photocatalytic cyanomethylarylation of N-aryl/benzoyl acrylamide for the synthesis of oxindoles and isoquinolinediones using diazonium salts and PIFA/1,3,5-trimethoxybenzene as radical initiators, respectively [29][30][31]. In this case, expensive Ru and 4CzIPN-based homogeneous

• acrylamide 7a (Scheme 7a). When the reaction was conducted in the presence of the radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO), both the desired product 8a and the byproduct 15 were not observed, which indicated that the reaction proceeds through a radical pathway (Scheme 7b). It is worth

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

• -butanesulfinyl imine 168. At the allylation step, a new chiral center with S configuration in compound 169 is formed in 96% yield. After removal the chiral sulfinyl group under acid conditions, treatment with acryloyl chloride produced acrylamide derivative 170. From this common intermediate, and after several

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• conditions, 3i–o were predominantly formed in 92–99% yields. Thus, we could obtain a wide variety of 3-phenylthio lactams bearing an amide functionality by electrophilic allylation with 1. Having completed the installation of an acrylamide side chain into 3-phenylthio lactams, we subsequently proceeded to

• bearing an acrylamide side chain as a common intermediate. Finally, we subjected methylene-lactone-fused spirolactams to the assay of cytotoxicity on P388 cells (Figure 2). N-Methyl-substituted spirolactam 5c exhibited potent cytotoxicity (IC50 0.32 μg/mL) which was comparable to that of the N-acetyl

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• of perfluoroalkyl [87], acyloxy [88], or alkyl [89][90] radicals to the carbon–carbon double bond of the N-(o-cyanobiaryl)acrylamide skeleton led to the construction of differently substituted pyrido[4,3,2-gh]phenanthridines. Photocatalytically generated amidyl radicals were adopted for a direct

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• storage and/or use of BTMS, which exposes it to traces of water. As mentioned in the previous section, compounds having multiple bonds could undergo an addition reaction upon exposure to HBr [42]. We studied this problem using 1H NMR spectroscopy with the model acrylamide 11 (Scheme 3), representing a

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• , acrylamide was used in an analogous manner to the carbamates employed by Veenstra (Scheme 1) [19]. In our initial attempts, the solvent was changed from dichloromethane to acetonitrile due to solubility issues with the acrylamide and the postulated imine intermediate. The reaction proved sluggish, taking

• , the ring-closing metathesis reaction worked nicely to give 9b in 99% yield. Having demonstrated the versatility of our approach, the synthesis of racemic aza-goniothalamin was attempted. Our synthesis began with cinnamaldehyde (Scheme 5), which was condensed with acrylamide under the same conditions

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• result being consistent with analogous reactions reported in the literature [22][23]. In the reaction with acrylic acid and acrylamide, substrate 1a was recovered, probably due to the propensity of these acrylic substrates to polymerization. In case of ethyl crotonate and methyl metacrylate, only traces

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• hydrazine 114 and sulfur dioxide (Scheme 33). Rearrangement of the so-obtained intermediate 119, through radical 120, would provide oxindole 115. The same acrylamide 113 (R1 = H) has been recently used in another multicomponent synthesis along with CO (23) and benzodiazepine derivative 121 under palladium

• prepared in moderate to good yields. A wide scope of aryldiazonium reagents 68 bearing electron-donating and electron-withdrawing groups worked well in the reaction, but when a pyridyl heterocycle was employed, the reaction failed. On the acrylamide side, activating and deactivating groups worked similarly

• sulfonylacrylamide 123 (Scheme 36). Then, ipso-cyclization of radical 125 to 126, departure of SO2 and final oxidation of 127 by Cu(II) would provide oxindole 124. As a consequence of this desulfonylative 1,4-aryl migration, the SO2 group initially present in the starting acrylamide is replaced by another SO2 moiety

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• for all micrographs in this figure. A simplified (and not in scale) representation of the ELLA assay, to study the interaction between GVs or micelles of compound 8 or 5 and WGA. OPD: O-phenylenediamine dihydrochloride; PAA: poly[N-(2-hydroxyethyl)acrylamide]. Inhibition curves for the binding of WGA

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• activation; rhodium; acrylamide; heterocycles; Introduction Over the last decade, transition metal-catalyzed C(sp2)–H activation has emerged as an efficient strategy to access complex molecules [1][2][3][4][5][6]. Among the methodologies, RhIII-catalyzed oxidative annulation of a C(sp2)–H bond with 2π

• 3b in 41% yield. Acrylamide afforded the corresponding indolizinone 3c in 43% yield. Compared to α-substituted acrylamides, β-substituted acrylamides performed the reaction with lower yields under the same conditions (3d–f). It should be pointed out that α,β-disubstituted acrylamides were also

• pathways, and the one from 2a is the minor pathway. The main pathway is directly from 1a. Based on the above results, a plausible mechanism is proposed in Scheme 4 [31]. C(sp2)–H activation of acrylamide 1a, followed by subsequent intramolecular coordination of the alkyne gives intermediate B. Subsequent

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• oxidation and dehydrogenation gives the target product 49. A new and first achievement for the synthesis of CF3-contained seven-membered ring compounds 55 and 56 through trifluoromethylation of acrylamide-tethered alkylidenecyclopropanes 54 was presented by Shi and co-workers (Scheme 13) [78]. The possible

• of MCPs with AgSCF3. oxidative radical ring-opening and cyclization of MCPs with α-C(sp3)-–H of ethers. Oxidative radical ring-opening and cyclization of MCPs with aldehydes. Cu(I) or Fe(II)-catalyzed oxidative radical trifluoromethylation/ring-opening/cyclization of MCPs derivatives (acrylamide

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• diastereoselectivities of 1,3-dipolar cycloadditions which allow to control stereochemistries at C3 and C5 [79][80]. To illustrate this concept the E/Z mixture of nitrone 70 was reacted with acrylamide 71 prepared from (2S)-bornane-10,2-sultam to afford mainly (20:1) the isoxazolidine (3S,5S)-72 easily separable from