Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• affected by both halogen type and metal insertion. In compound 1 the main motifs seen are the face-to-face stacking at 3.326(4) Å (Figure 2A) and the tilted edge-on interaction (≈64°) (Figure 2B). The other motif seen is the inline interactions where layers of porphyrins are lined up with the bromine atoms

• porphyrin conformation are observed due to the metal center insertion. The first of these is the stacking between the porphyrin rings (at 3.581(3) Å), which now features the bromine atoms pointing in opposite directions with a ruffled conformation of the porphyrin macrocycle (Figure 3A). Moreover, a similar

• between compound 1 and 3 due to an increase in the saddle (B2u) conformation, while little change has occurred in the in-plane (IP) with a moderate increase in the B2g. While an increase in the size of the substituted halogen has a moderate effect, a much larger effect is observed due to metal insertion

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• progresses under neutral conditions. The authors postulated that the vacancy on the square-planar Pd(II) species allows a faster alkene insertion in comparison to Pd(0). The cationic Pd(II) enolate exists as a dynamic mixture of C- and O-bound enolate and is highly susceptible to hydrolysis. This means that

• migratory insertion via TS1 (Scheme 13). The stereochemistry is controlled mainly by the hydrogen repulsion of the methylene group neighbouring the keto group of the enone with the t-Bu group of the ligand L9. Another interesting example for the application of this reaction in the preparation of precursors

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• , two main synthetic strategies are used to prepare these analogues. One requires the insertion of the alcohol and amino groups in the α,β position with the correct stereochemistry [17][18][19][20]. The second strategy involves a bond formation between two chiral centers to produce the targeted 2-amino

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• many bioactive heterocycles [36]. These are also important precursors of diazo adducts which are used in insertion, cyclopropanation, and various rearrangements to construct various cyclic as well as acyclic moieties under metal-catalysed conditions [37][38]. On the contrary, under basic conditions

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• -bromobenzoate via palladium-catalyzed isocyanide insertion [32][33] (a method that is limited to tertiary-substituted isocyanides) or 2) the palladium or copper-catalyzed coupling of bromolactams with amines (a method that requires the usually lengthy synthesis of the bromoprecursors) [19][34]. Therefore, the

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• , reflecting the insertion in the DPPC monolayer. The higher the degree of fluorination, the higher the amount inserted, with a maximal efficiency observed for lipopeptide 3 (C8F17). However, the behavior of the F-lipopeptide 2 with an odd number of carbon atoms (C7F15) is closer to that of 1 (C6F13) than to

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• dichlorophosphites followed by alcoholysis with hydroxy esters, the phosphinylation of hydroxy esters with phosphonochloridites followed by oxidation, and the carbene insertion of N-protected amino acids with 1-diazoalkylphosphonates. This review includes the synthesis of α-, β-, and γ-phosphonodepsipeptides and

• insertion reactions. The reaction of the N-protected amino acids 209 and 210 with diethyl 1-diazo-2,2,2-trifluoroethylphosphonate (211) gave rise to the trifluoromethyl-containing phosphonodepsipeptides 212 and 213 with C-1-hydroxyalkylphosphonic acids in good yields under the catalysis of dirhodium

• tetraacetate (Scheme 39) [60][61]. To develop novel bone-targeting prodrugs, a copper-catalyzed carbene insertion of tetraethyl diazomethyldiphosphonate (216) with N-Boc-protected amino acids 214 and 215 provided a simple method to synthesize phosphonodepsipeptides 217 and 218 containing a C-1

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

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

• cations is probably the α-(trifluoromethyl) carbocation. Many efforts are currently devoted to develop methods allowing the efficient insertion of fluorine atoms or fluorinated groups into organic molecules [7][8][9][10][11][12]. The increasing demand for fluorinated scaffolds, due to the striking

Supramolecular polymers with reversed viscosity/temperature profile for application in motor oils

• Jan-Erik Ostwaldt,
• Christoph Hirschhäuser,
• Stefan K. Maier,
• Carsten Schmuck and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2021, 17, 105–114, doi:10.3762/bjoc.17.11

• performed structural modifications in order to increase the solubility. Keeping the BINAM backbone and the ACP binding unit, we performed two modifications (as described above, see Figure 2b): First, the linker unit was extended by insertion of a benzyl-protected glutamic acid between the BINAM core and the

• specific viscosity decreases significantly upon increasing the temperature (the same was also observed in toluene solution, see Supporting Information File 1, chapter 6.3.2). Thus, the modification of the linking unit by insertion of one amino acid (to give compound 3) has a detrimental effect on the RVT

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• trifluoromethyl compounds under the same reaction conditions. A reaction mechanism is proposed. Keywords: acyl fluorides; deoxyfluorination; fluorine; solvent-free; trifluoromethyl group; Introduction Due to an impressively wide effect of fluorine on the biological activity, the insertion of fluorine atoms or

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• enhanced and blue-shifts after affinity/recognition in a polar solvent. Several computational studies confirmed that the spectral change is caused by the insertion of the environment-sensitive fluorophore in the hydrophobic domains/grooves of the target protein/DNA (Figure 1A). The major problem of these

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• caffeine, claimed in the patent literature [19][20] and 7-difluoromethyl caffeine, prepared by the insertion of difluorocarbene into the N–H bond of theophylline (7) [11][21][22]. Similar to the reaction of tetrakis(trifluoromethyl)-1,3-dithietane (1) and theophylline (7, Scheme 5), this process also led

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• formed during the cyclization reaction of 16 compared to phenyl nitrene [42]. Besides H-SN4 13, which is formed by insertion of the nitrene N-atom into the C3–H σ-bond of the thienothiophene in 16 and simultaneous migration of the H-atom to the nitrogen, mostly undefined black oligomeric or polymeric

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

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

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• -fluoroalkylated indanones are shown in Scheme 5 [28][38]. Thus, the reaction presumably proceeds as follows: (1) transmetalation of the cobalt catalyst with 2-formylphenylboronic acids (2) gives the arylcobalt species Int-1, (2) insertion of the alkyne 1 into the [Co]–Ar bond (see Int-2a) [39], (3) migration

• insertion into the formyl moiety to afford the corresponding cobalt alkoxide Int-3a, (4) protonation of Int-3a with HX (X = acac, OiPr, or OH), giving rise to the desired 2-fluoroalkylated indenol 3. The formation of the 3-fluoroalkylated indanones as a side product may be explained based on the previous

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• both, the minor and major groove of the polynucleotide. Such bulky groups positioning requires the DNA double helix to shortly open at a binding site and close upon threading intercalator insertion. Also, the chosen NDI chromophore is characterised by easily tuneable emission wavelengths [23], and

Three new O-isocrotonyl-3-hydroxybutyric acid congeners produced by a sea anemone-derived marine bacterium of the genus Vibrio

• Dandan Li,
• Enjuro Harunari,
• Tao Zhou,
• Naoya Oku and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1869–1874, doi:10.3762/bjoc.16.154

• (Figure 3a). Note that the sign distribution of the Δδ(S − R) values in β,β-substituted carboxylic acids is inverted from that observed in the α,α-substituted counterparts (Figure 3b) because the PGME anisotropy group is flipped upside down due to the insertion of an extra methylene group between the

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

• electron transfer to complete the catalytic cycle and regenerate the active catalytic species. The classical Fujiwara–Moritani reaction promoting the addition of arenes to olefins illustrates a general mechanism for such traditional C–H functionalization (Figure 4, left) [70][71][72]. The insertion of a

• metal catalyst X2M into an aromatic C–H bond of a substrate (generally facilitated by the presence of a directing group (DG)), delivers a metal–aryl complex. Coordination and subsequent insertion of an alkene into the M–aryl bond then provides the desired coupling product after β-hydride elimination

• , isolated in moderate to good yields. A possible gram scale-up synthesis was also accomplished. Within the mechanistic cycle, after initial vinylic C–H bond activation and insertion of CO into the C–Pd bond, the acylpalladium intermediate is converted into its conjugated analog under DABCO assistance

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• excellent light-emitting properties with quantum yields (ΦF) up to 47%. Keywords: benzothiophene; β-carboline; metal-free; photophysical properties; sulfur insertion; Introduction The pyrido[3,4-b]indole moiety, commonly referred as β-carboline, is the core unit of about one quarter of all natural

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

• stereochemical outcome of the overall process. A carbon monoxide ligand then undergoes migratory insertion into one of the Co–C bonds in cobaltacycle V, followed by reductive elimination to release the final product (Scheme 3). As mentioned above, the regiochemistry of this transformation is, in most cases

• , predictable for unsymmetrical alkynes (things are more complex regarding the olefin). Generally, the most sterically encumbered substituent of the alkyne occupies the proximal position in the enone system. This is dictated by the migratory insertion of the olefin into the most accessible Co–C bond (Scheme 3

• groups of comparable steric demand at both ends of the alkyne, electronic effects come into play. Here, the more electron-rich substituent occupies the α position, and the more electron-poor the β position (Scheme 4). This selectivity could be rationalized by the insertion of the olefin into the weakest

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• constitute a severe limitation in the employ of BER [2][3][4]. To minimize these drawbacks, its isoquinoline portion was derivatized in positions 9 and 13 that are critical for topoisomerase inhibition and quadruplex structure binding [5][6][7][8]. The insertion of a phenyl group or a benzhydryl group linked

• insertion in the original molecule of different functions with their own peculiar features. Often, the biological properties of the resultant derivatives are not simply attributable to the sum of the characteristics shown by the individual moieties, but synergistic effects can increase their effectiveness

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

• biaryls 5.1a–d in up to excellent yields at room temperature by using α-bromoesters as radical precursors and [fac-Ir(ppy)3] as the photoredox catalyst [49]. A similar photocatalyzed tandem insertion/cyclization approach based on isocyanides and amino acid/peptide-derived Katritzky salts as precursors of