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

• catalyst 15 to yield the trimerized products 12 (syn) and 13 (anti) in respectable yields (Scheme 2). The alkene-bridge exchange of 12 (syn) was accomplished by tandem ring-opening and ring-closing metathesis (ROM–RCM) in the presence of Grubbs’ first generation (G-I) catalyst to generate a C3-symmetric

• 27 in a single step. They also pointed out that when ethylene gas was used as an alkene source for the ring-opening step, diluted reaction conditions were necessary to dissolve the ethylene in dichloromethane to avoid polymerization. Therefore, after several experimentations, they noticed that liquid

• Z-oct-4-ene in toluene was found to be a more effective alkene source for the ring-opening reaction in comparison to the gaseous ethylene, as it increases solubility and also improve the lifetime of the catalyst. 2.1 Derivatization at benzylic position As can be inferred from the architecture of

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• yielding a dihydronaphthalene 16. Formally speaking, 15 results from a [2 + 2] cycloaddition and 16 from a [4 + 2] cycloaddition (Diels–Alder reaction). Under the reaction conditions, cyclobutene 15 undergoes a fast electrocyclic ring opening leading to a butadiene 17, which is finally transformed into 2

• -disubstituted cyclobutene 15d and subsequent conrotatory electrocyclic ring-opening, from which Z(1,2),E(3,4)-configured butadiene intermediate 17d results. The intermediacy of a cyclobutene 15 in the mechanistic scenario of Scheme 5 is corroborated by the isolation of cyclobutene 18 from the reaction of 1a

• with the expected orientation of the cycloaddition. Cis-annelated cyclobutene 18 (1H NMR: 3JH,H = 3.8 Hz for the angular protons) and the iminium-substituted primary cycloadduct are not expected to undergo a fast ring opening under moderate thermal conditions, because the orbital-symmetry-allowed

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

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

• 110. In a fashion similar to that used by Ghosh’s group, the VO(acac)2-catalyzed epoxidation of 110 afforded the spirocyclic oxirane 111. A subsequent ring opening with LiCl gave 112, which was used in the synthesis of thailanstatin B (5). Nicolaou’s route to 111 (9 steps, 29.9% yield) is shorter and

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• Clement Q. Fontenelle Thibault Thierry Romain Laporte Emmanuel Pfund Thierry Lequeux Normandie Université, Laboratoire de Chimie Moléculaire et Thioorganique LCMT UMR 6507, ENSICAEN, UNICAEN, CNRS, 6 Bd. du Maréchal Juin, 14050 Caen, France 10.3762/bjoc.16.160 Abstract The selective ring-opening

• -opening reaction with bromide ions, even in the presence of bulky substituents. Keywords: acyclonucleotide; fluorine; monofluoroalkene; oxetane; selective ring-opening reaction; tetrasubstituted alkene; Introduction The introduction of fluorine atoms into organic compounds is known to modify their

• envisioned an alternative approach starting from fluoroalkylidene-oxetane derivatives and to the end we have studied the selectivity of the oxetane ring-opening reaction (Figure 3). Results and Discussion The preparation of a series of fluoroalkylidene-oxetanes 1–3 was previously reported from 3-oxetanone

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• pharmaceutical products [15]. Moreover, they are used as electrolyte components in Li-ion rechargeable cells and as aprotic polar solvent with high boiling point as alternative of dangerous solvents because of their good biodegradability and low toxicity [16][17][18]. Synthetic intermediates for ring-opening

• performed. Formation of oxazolidinone 9f There are two possible channels for the cyclization reaction of epoxide 7f with CSI to form oxazolidinone intermediates 10 and 11 as shown in Figure 1. In both transition states it is found that the ring-opening reaction of the epoxide, a nucleophilic attack of N4

• ′ (Figure 2). Therefore, attack by N4 of CSI on the C2 of epoxide is found to be energetically the most favored approach. The epoxide ring opening and formation of the O–C(=O) bond are almost completed before the C–N bond is formed. The changes in bond lengths along the intrinsic reaction coordinate (IRC

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• the β-disaccharide 16 (Scheme 2). A ring-opening reaction followed by subsequent glycosylation of 19 with orthogonally protected thioglucoside 10 gave trisaccharide 21 in moderate yield. To improve the yield, the nucleophilicity of the disaccharide acceptor 19 (Scheme 2) was altered by replacing the

• benzoate esters in 16 by a benzyl ether leading to compound 17. The latter then was converted into the more reactive acceptor 20 via a ring-opening reaction. Glycosylation of 20 with thioglucoside 10 resulted in the desired trisaccharide 22 in almost twice the yield when compared to trisaccharide 21

• was modified into compound 6 via benzylidene ring opening followed by benzoylation of the free C-4 secondary hydroxy group in 27. The disaccharide imidate 29 was synthesized from 6 by anomeric desilylation to afford 28 that was converted to the corresponding imidate in an excellent yield. The final [2

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• to afford intermediate isoindole 4a [2][3][4][5][6]. Then, the addition of water to the sterically less-hindered site of the latter compound followed by ring opening resulted in the rearranged aldehyde 2a [1]. As regards the formation of dimer-like product 3a, the tendency of pyrrole [7][8], indole

• case of isoindoles is that the attack of water at cation 19 and subsequent ring opening did not happen here. DFT calculations The proposed mechanism of the 1→2 rearrangement (Scheme 4) was investigated in detail by DFT level quantum chemical computations using the Gaussian 09 program package [19

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• -aroyloxyaldehydes and trifluoroacetophenones, followed by ring opening with an amine or a reducing agent is described. The resulting β-trifluoromethyl-β-hydroxyamide and alcohol products are produced with reasonable diastereocontrol (typically ≈70:30 dr) and excellent enantioselectivity, and they can be isolated in

• moderate to good yield as a single diastereoisomer. Keywords: enantioselective catalysis; formal [2 + 2] cycloaddition; N-heterocyclic carbene; ring opening; trifluoromethyl group; Introduction The trifluoromethyl unit holds a prominent and privileged position within organic chemistry [1][2][3][4][5][6

• the NHC-catalyzed formal [2 + 2] cycloaddition in THF, a subsequent ring opening step with allylamine was investigated. Although the diastereomeric ratio of the resultant crude reaction mixture was 75:25 after chromatographic purification, as seen by NMR analysis, the corresponding β-trifluoromethyl-β

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

• α‐carbonyl radicals was likewise reported [50]. On the contrary, the Mn(acac)3 photocatalyzed ring opening of cyclopropanol 6.2 gave an easy access to a β‐carbonyl radical 6.5·, which in turn added onto 2-biphenyl isocyanide 6.1 to give the corresponding 6-β-ketoalkyl phenanthridine 6.3 in a good

• turn gave intermediate 8.4· upon cyclization onto the methylenecyclopropane double bond. Ring opening of the strained cyclopropyl ring liberated an alkyl radical (in intermediate 8.5·) that readily cyclized onto the adjacent aromatic ring to give 8.6 in a good yield. The oxidation of 8.6 under radical

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• ring opening. In the case of anhydrides 6 and 7, a 6-exo-trig ring-closure reaction of the tautomer form 30a leads to the observed products 25 and 26, according to the plausible mechanistic suggestion presented in Scheme 7. In the case of compound 27 (X = direct bond), the reaction could be

Synthesis of new fluorescent molecules having an aggregation-induced emission property derived from 4-fluoroisoxazoles

• Kazuyuki Sato,
• Akira Kawasaki,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2020, 16, 1411–1417, doi:10.3762/bjoc.16.117

• or from isoxazoles 2 through a ring-opening reaction (Scheme 3). Based on the above observations, we attempted to introduce a fluorine atom into BKIs to access the corresponding α-fluorinated boron ketoiminates (F-BKIs, 9). First, we started from 1,3-diketones 1 and reacted them with ammonium formate

• diketone (Scheme 5). As an alternative method to synthesize F-BKIs 9, we turned our attention to the ring-opening reaction of isoxazoles. The reductive cleavage of the N–O bond in isoxazoles can be achieved by transition metals or their complexes to give the corresponding enaminoketones [35][37

• ]. Consequently, we examined several conditions for the ring opening of fluorinated isoxazoles 3, and found that using Mo(CO)6 gave the corresponding α-fluorinated enaminoketones 8 in moderate yields (Scheme 6). With the enaminoketones 8 at hand, the subsequent boron complexation with BF3·Et2O in the presence of

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• converted into 3,5-anhydro-3-thiopentofuranosides 135 through a Mitsunobu reaction with thiolacetic acid and hydrolysis followed by an intramolecular nucleophilic ring-opening of the oxirane ring. The newly generated thiolate underwent a nucleophilic ring-opening of the oxirane to generate the thietane ring

• [55] (Scheme 26). After the ring-opening of methyl 2,3-anhydro-α-D-ribofuranoside (133a) with NaOMe, following a sequence of a Mitsunobu reaction, mesylation, and treatment with sodium bicarbonate, another 3,5-anhydro-3-thiopentofuranoside 138 was prepared [51] (Scheme 26). The 2-amino-3,5-anhydro-3

• -thiofuranoside 141 by reduction with triphenylphosphine [55] (Scheme 27). 2.2.3 Synthesis via the nucleophilic ring-opening of three-membered heterocycles and subsequent displacement from halomethyloxirane derivatives: Chloromethyloxirane (142a) and its 2 and 3-phenyl derivatives 142b and 142c reacted with H2S

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

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

• excited state, together with an intense absorption in the visible-light region. The transformation proceeds via the single-electron oxidation of 2H-azirines, forming a nitrogen-centered radical cation, which is prone to ring opening. The driving force of the ring strain release and irreversible ring

• performs an SET oxidation of an cyclopropylaniline 36.1, leading to an N-centred radical cation after ring opening. The latter undergoes a [3 + 2] annulation with cyclopropenes 36.2, affording a bicyclic product 36.3. The key to the broad substrate tolerance relied on using 4DPAIPN (OD7), which is a mild

• carboxylates. Aminyl and aminium radical generation The prevalent strategy for accessing aminium radicals is SET oxidations. The efficiency of this approach is closely related to the stabilization of the generated radical on the substrate (delocalization, electronic effects) or through a strain release ring

The charge-assisted hydrogen-bonded organic framework (CAHOF) self-assembled from the conjugated acid of tetrakis(4-aminophenyl)methane and 2,6-naphthalenedisulfonate as a new class of recyclable Brønsted acid catalysts

• Svetlana A. Kuznetsova,
• Alexander S. Gak,
• Yulia V. Nelyubina,
• Vladimir A. Larionov,
• Han Li,
• Michael North,
• Vladimir P. Zhereb,
• Alexander F. Smol'yakov,
• Artem O. Dmitrienko,
• Michael G. Medvedev,
• Igor S. Gerasimov,
• Ashot S. Saghyan and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2020, 16, 1124–1134, doi:10.3762/bjoc.16.99

• , including the ring opening of epoxides by water and alcohols. A Diels–Alder reaction between cyclopentadiene and methyl vinyl ketone was also catalyzed by F-1 in heptane. Depending on the polarity of the solvent mixture, the CAHOF F-1 could function as a purely heterogeneous catalyst or partly dissociate

• , providing some dissolved F-1 as the real catalyst. In all cases, the catalyst could easily be recovered and recycled. Keywords: Brønsted acid catalyst; charge-assisted hydrogen-bonded framework; Diels–Alder; epoxide ring opening; heterogeneous catalyst; Introduction Tremendous successes in homogeneous

• catalyst for the Brønsted acid-catalyzed ring opening reactions of epoxides with alcohols and water, with the latter reaction occurring in a three-phase medium. In addition, a Diels–Alder reaction was promoted by F-1 in heptane. Results and Discussion Mixing together aqueous solutions of two equivalents of

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

• necessary in order to obtain a clean release of the truxillic esters. In addition to the methoxycarbonylation of the Pd–C, the reaction also involves ring opening of the oxazolone moiety to afford the corresponding ester and amido groups. This ring opening was also observed in the case of the hydrogenation

• spectra show in all cases the presence of two different CO2Me units and one N(H)C(O)C(H)=C(H)Ph moiety, thus demonstrating the incorporation of the methoxycarbonyl group and the ring opening of the oxazolone by methanol. The expected signals for the aryl and cyclobutane rings are also observed. These

• -diaminotruxillic bis-amino acids. The reaction of the cyclobutanes 4 with CO (1 atm) in MeOH/NCMe results in the ring opening of the oxazolone group, methoxycarbonylation of the Pd–C bonds, reductive elimination, and finally release of the 1,3-diaminotruxillic bis-amino esters 5 as single isomers (ε-isomer). The

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

•  29). 2.4. Fluorodehydroxylation of β-hydroxyphenylalanine Alternatively, Kollonitach et al. prepared racemic 3-fluorophenylalanine (136) through the fluorodehydroxylation of 3-hydroxyphenylalanine (137) using sulfur tetrafluoride (SF4) in HF [67] (Scheme 30). 2.5. Ring opening of aziridine

• derivatives by HF/Py The ring opening reaction of aziridines 138a,b by treatment with hydrogen fluoride in pyridine afforded 3-fluorophenylalanine esters 139a,b. The subsequent enzymatic hydrolysis of esters 139a,b gave the threo-isomer 136 in an enantiomerically pure form [68][69] (Scheme 31). On the other

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• access various derivatives, such as 12 and 13, derived from the trapping and Baeyer–Villiger oxidation of 11, respectively, or compound 16, obtained via the ring opening reaction of 15 with an amine (Scheme 5). Taking the enolate intermediate derived from the addition of EtMgBr to coumarin as an example

• reaction, two seven-membered heterocyclic bisphosphates (O- and N-containing, respectively,) underwent Cu/L15-catalysed AAAs and provided the corresponding chiral products with good yield and high enantioselectivity (92–93% ee) [40]. Ring opening reactions where carbon–carbon bonds are formed upon the

• addition of organometallics to heterocyclic acceptors, resulting in products that are not heterocyclic, provide an alternative strategy to generate important building blocks with two stereocentres, starting from heterocyclic substrates. The copper-catalysed ring opening of oxygen-bridged heterocyclic

Suzuki–Miyaura cross coupling is not an informative reaction to demonstrate the performance of new solvents

• James Sherwood

Beilstein J. Org. Chem. 2020, 16, 1001–1005, doi:10.3762/bjoc.16.89

• , caution is advised in the presence of nucleophilic reagents, as this has previously been reported to cause ring opening of propylene carbonate during Suzuki–Miyaura cross couplings [7]. In this work no decomposition of propylene carbonate was identified. Using only water as a solvent is also appealing

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• might come from ring opening [20][21]. Conclusion In summary, we have developed a new workflow allowing to efficiently perform photoredox-nickel dual-catalyzed reactions in parallel for fragment-based library generation. We have screened 29 combinations of complex spirocyclic amines and (hetero)aryl

Cation-induced ring-opening and oxidation reaction of photoreluctant spirooxazine–quinolizinium conjugates

• Phil M. Pithan,
• Sören Steup and
• Heiko Ihmels

Beilstein J. Org. Chem. 2020, 16, 904–916, doi:10.3762/bjoc.16.82

• a certain extent Hg2+) initially induced a ring-opening reaction that was irreversibly followed by a fast ring closure–deprotonation–oxidation sequence to give styryl-substituted naphthoxazole derivatives as the products quantitatively. For the quinolizinium-substituted spirooxazine derivative, the

• ., 1aSO: λabs = 317 nm, 1aMC: λabs = 602 nm, in MeCN) [16]. In some instances, the ring-opening reaction may also be induced in the dark through the addition of particular metal cations that are able to coordinate to the phenolate oxygen atom and/or other additional coordinating atoms and substituents

• that have been introduced into the structure of the spirooxazine and spiropyran derivatives [17][18][19][20][21][22][23][24][25][26]. Regardless of whether the ring-opening reaction is induced by cations or irradiation, the coordination of metal ions to the substrate usually results in a negative

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• chiral cyclobutene 180, providing highly functionalized cyclobutanes 182 and an access to the enantioenriched cyanosulfones 183, resulting from cyclobutane ring opening, or the new tetrasubstituted cyclobutanes 184 (Scheme 42). The cyclobutenes 180 were subjected to a photocatalyzed radical addition, and

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• PhMe2Si group could also be prepared in moderate yield (276). The regiocontrolled ring opening reactions of the same aryl-substituted aziridines 277 have also been shown by Minakata and Takeda et al. to be susceptible to dual Pd/Cu catalysis. Depending upon the ligand on each metal, either the 2 or 3

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• free aziridine 5a in 81% yield while maintaining the ee value. The reduction of the carbonyl moiety with either NaBH4 or LiAlH4 produced hydroxy-substituted CF2-functionalized aziridine 5b in excellent yield with exclusive diastereoselectivity [47]. Furthermore, the ring-opening of 4a under acidic