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

• chromone derivative for the total syntheses of (−)-caesalpinnone A and (−)-caesalpinflavan B (Scheme 12) [9]. Mechanistic studies of this catalytic system were also made by Stoltz’s group. A linear relationship between the ee of the catalyst and the product has been found [48]. That means that the

• catalytically relevant species is monomeric Pd–PyOx. This was further supported by a mass spectrometric study [52]. The catalytic cycle was also suggested in accordance with DFT calculations and mechanistic studies (Scheme 13) [48][49]. The key step for both, the enantioselectivity and turnover, is the

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

• carbonyl electrophilicity [105]. The use of chiral Lewis acids can induce asymmetry [106]. Yoon et al. applied this well-known form of catalysis to a photocatalytic system using enones 269 and 270 (Scheme 43a) [107]. Mechanistic studies of a closely related achiral reaction [20], showed this reaction

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• position; ketene; mixed chromophores; Introduction Enones exhibit a rich and diverse photochemistry. The deep-seated photochemical rearrangements found in these systems have attracted numerous mechanistic studies. In this context, the photochemistry of α,β-enones A and β,γ-enones B (Figure 1) has become

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

• : Here, we briefly summarize the importance of fluorine atoms in organic molecules in the context of medicinal chemistry, materials chemistry, analytical chemistry and in the mechanistic studies of synthetic reactions. The importance of fluorination reactions in organic synthesis is reviewed exhaustively

• (sp3)–H fluorination mechanistic studies: In order to unearth a greater understanding of their previously-reported photosensitized C(sp3)–H fluorination, Tan, Lu, Soo and co-workers employed a nanosecond-scale transient absorption (TA) spectroscopy and time-dependent density functional theory (TDDFT

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

• photoredox catalysis (Figure 5) [73]. The coupling products were generally isolated in good yields, although this procedure required high temperature (120 °C). Remarkably, molecular oxygen was used as the terminal oxidizing agent of the overall C–H functionalization reaction. The mechanistic studies revealed

• synthetically meaningful σ-bromo esters. The mildness of the reaction conditions warranted tolerance of sensitive and/or biologically relevant sugar, menthol, and steroid motifs (Figure 37). The mechanistic studies conducted by Ackermann et al. clearly showed that the metallacyclic intermediates resulting from

• synthesis. The mechanistic studies suggested a unique mode of action of this catalytic system (Figure 45). In the initial step both aromatic coupling partners coordinate to the Mn catalyst, thus generating a photoactive complex. Visible-light photoexcitation of the Ar–Mn species and subsequent electron

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• transition metal coordination sphere; the energy of a new M–C bond formed and the thermodynamic stability of organometallic product. With new developments in computational chemistry, mechanistic studies using density functional theory (DFT) provide valuable insights into the reactivity of organometallic

Recent synthesis of thietanes

• Jiaxi Xu

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

• mechanistic studies. The reactivity of the substituted allenes towards triplet aromatic thiones was investigated. The product analysis revealed the formation of thietanes and occasionally of [4 + 2] cycloadducts (thiopyrans) generally in high overall yields. Steady-state measurements showed that electron

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

• of the richest families of stable and persistent organic radicals with applications ranging from catalysis of selective oxidation processes and mechanistic studies to production of polymers, energy storage, magnetic materials design and spectroscopic studies of biological objects. Compared to other N

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

• converted the aryl and alkyl α-keto acids 17.1 to the 3-acylindoles 17.3 using rose bengal (OD15) as a photocatalyst under aerobic conditions. Mechanistic studies suggest that rose bengal (OD15) acts as an energy transfer sensitizer generating singlet oxygen. The authors proposed that the latter would be

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

• catalytic amination of (E)-cinnamic acid The enzyme phenylalanine aminomutase (PAM) from Taxus chinensis catalyzes the stereoselective isomerization of α-phenylalanine to β-phenyalanine 111a–c. Mechanistic studies showed that (E)-cinnamic acid is an intermediate in this transformation [63]. Accordingly

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

• coupling. Specific mechanistic studies whereby the rate limiting step or mechanism changes according to the solvent remain a valid pursuit, as does measuring the palladium contamination in products [23]. However, the works of Watson [24], Denmark [25], and others [26][27], have already elucidated many of

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• -rich and electron-deficient groups in the arylsulfinic acid and alkyl sulfinates, such as sodium ethylsulfinate and sodium methylsulfinate (Scheme 19). The authors also showed that the methodology can be applied to the sulfonation of steroid drug arimistane in 45% yield (Scheme 20). The mechanistic

• studies on this reaction are ongoing with initial suggestions of the coupling between the sulfonyl radical and the radical alkene as a key step for this transformation. In 2019, Ghaffari-Moghaddam, Oveisi and co-workers reported the synthesis of a new multifunctional MOF, namely Fe@PCN-222(Fe), and its

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

• indolinonaphthoxazoles. Herein, we present the synthesis of, and investigation on the conjugates 3a and 3b, as well as mechanistic studies on the metal ion-induced formation of the derivatives 4a and 4b, along with the pertinent spectroscopic data of the products. Results and Discussion Synthesis The spirooxazine

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• to benzoxepines and 2,2’-biphenols through catalyst control (Scheme 5, top) [20]. Extensive mechanistic studies evidenced a biomimetic pathway involving a key CuII-semiquinone intermediate in which the substrate becomes activated as a redox-active ligand (Scheme 5, bottom) [21]. This radical CuII

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

• irradiation, supporting the other two pathways. Also, mechanistic studies by Cui et al. showed that the energy levels of the reactions (1) and (2) in Scheme 5 were closely tied, so distinguishing them is not always trivial [32]. The triplet state quenching of 8 and related compounds, such as aryl ketones, has

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• more and more dominant role as the catalysis of the 3-phospholene oxide (1) 2-phospholene oxide (4) rearrangement, which explains the change in the reaction rate in the kinetic experiments. Mechanistic studies of the isomerization of 3-phospholene oxides 1 under acidic conditions The isomerization of 3

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

• featuring a 1,4-borylation of α,β-unsaturated compounds 405 was reported by Hosomi in the presence of Cu(OTf)2·C6H6/(t-Bu)3P in DMF. No reaction occurred using (CuOTf)2·C6H6 in the absence of (t-Bu)3P. Mechanistic studies showed that the coordination of phosphorus(III) to Cu(I) accelerated the reaction, as

• an appropriate electrophile led to C–C bond formation, ultimately delivering chiral tertiary alcohols. Mechanistic studies and DFT calculations showed that an in situ-formed borylcopper(I) species is responsible for the 1,2-addition (Scheme 73) [136]. C,O-Diboration of ketones 464 was explored using

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• isolated in moderate to good yields. Using the more reactive allyl sulfone, a panel of symmetrical diaryliodonium salts was reacted, giving the products in good yields. The authors conducted some mechanistic studies and suggested a plausible catalytic cycle involving [Cu(I)]/[Cu(I)]*/[Cu(II)] species. The

• conducted mechanistic studies and demonstrated the role of [Cu(dap)2]Cl as a precatalyst since the catalytically active species was a [Cu(II)] complex. To explain the formation of the product, the authors suggested that after excitation, the [Cu(I)] catalyst is oxidized to a [Cu(II)] species along with the

• , probably due to their intrinsic reduction potential. Interestingly, the bromide substrate derived from menthol was readily reduced in an excellent 74% isolated yield. The authors conducted some mechanistic studies (including cyclic voltammetry and Stern–Volmer quenching experiments, for instance), and

Room-temperature Pd/Ag direct arylation enabled by a radical pathway

• Amy L. Mayhugh and
• Christine K. Luscombe

Beilstein J. Org. Chem. 2020, 16, 384–390, doi:10.3762/bjoc.16.36

• paper, we investigated the mechanism of room-temperature direct arylation and DArP by extending the method reported by Larrosa to synthesize a conjugated polymer, polyindole (PIn). Small molecule mechanistic studies were undertaken that will help future development of mild, efficient DArP conditions

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• sulfonylethanone oxime derivatives were less reactive than the PNP one [10]. Due to the similarity in DNA photocleavage by p-pyridine amidoxime, ethanome oxime and aldoxime carbamoyl derivatives, mechanistic studies were performed for two active compounds from the series of amidoximes and aldoximes, 12 and 26

• derivatives, of both amidoxime, ethanone oxime and aldoxime derivatives showed, similarly, significant DNA photocleavage. Mechanistic studies on DNA photocleavage showed that these “synthetic nucleases” act independently of oxygen and pH. As photobase generators, upon the homolysis of their N–O bond, oxime

• 32.3% of the initial EB–DNA fluorescence intensity for 11 and 31.5% for 12). DNA photocleavage of amidoxime carbamates at a concentration of 500 μM and mechanistic studies of aldoxime carbamate 26. Gel electrophoreses pictures. For (A) and (B) wells 1 and 2 represent DNA in dark and DNA UV irradiated

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• ]. From mechanistic studies it can be inferred that the photoredox catalysis process is independent from the C–H activation process. They also successfully demonstrated the importance of a photoredox catalysts in the generation of superoxide radicals. On the other hand, recently, Xiong and co-workers

• competent organic photoredox catalyst 9,10-dihydroacridine (1) under mild conditions at room temperature [128]. As usual, no reaction was observed without photoredox catalyst 1 or LED light. Mechanistic studies showed that the reaction proceeded via the generation of an aryl radical. As such, a list of

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• . Mechanistic studies have unambiguously proven the heterogeneous nature of the catalysis. The ability of the nanocatalyst to activate the C–H bond is due to the presence of minimal stabilising groups on its surface. Studies of the surface morphology of the catalyst have revealed the presence of surface oxides

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• azobenzenes or styrylbenzothiazoles) is desirable, in particular for cell-free mechanistic studies [33]. More broadly, this work also shows that the HTI scaffold robustly enables the photoswitchable use of resonance-capable substituents that can establish high-affinity interactions (such as para-hydroxy

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• control experiments and DFT calculations. Keywords: Brønsted and Lewis acids; DFT; mechanistic studies; rearrangement; stereochemistry; sulfur atom migration; Introduction Among all organic reactions, rearrangements are an exciting class of transformations where unusual or even unexpected products can

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• yields are given. Control experiments for mechanistic studies. Proposed reaction mechanism. Application of the reported method to the synthesis of frutinone A. Optimization of reaction conditions.a Supporting Information Supporting Information File 586: Synthetic details and compound characterization