Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• KOH using TBAB as a suitable phase transfer catalyst in a biphasic medium at room temperature. The scalability of the reaction has also been demonstrated. Our future efforts will involve performing an asymmetric version of this reaction using chiral phase-transfer catalysts and the results will be

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• -based catalysts (Fe, Mg, Ca, Ni, Zn, Pd, Li, Na [57] or Pd, Ru [61]). Unsaturated compounds were also applied as starting materials for 1,2-difluoroethylene preparation. Thus, chlorine atoms in 1,2-dichloro-1,2-difluoroethylene (CFO-1112) could be removed through the action of hydrogen and metal

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• overall applicability. A different approach for the synthesis of α-amino acids involves the formation of dehydroamino acids and subsequent hydrogenation [13][14]. More recently, there have been reports of techniques that utilize phase transfer catalysts (PTCs) to alkylate glycine derivatives [15][16]. A

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• metal reagents, including cobalt [10], copper [11], rhodium [12][13][14], palladium [15][16][17], silver [18], and gold [19] catalysts, have been reported. However, compared to the widespread use of metal catalysts, the synthesis of isoquinolinone scaffolds mediated by environmentally friendly

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• diazomonomalonamides under the action of various catalysts which is a very efficient method for preparing β-lactam esters [22][23][24][25]. At the same time, from the point of view of easy variation of the substituent in the exocyclic acyl group (RX), a method allowing the introduction of this moiety at the last step

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• , however, GBB has different features, either advantageous or not. Certainly, the most negative aspect of the GBB reaction is that, compared with the others, it usually requires more drastic reaction conditions. For this reason, many studies have been carried out aimed at the discovery of new catalysts to

• that time, along with some 30 solvents. The most widely used conditions, however, remained those originally discovered by Groebke, Blackburn and Bienaymé, namely the use of Sc(OTf)3, perchloric acid or p-toluenesulfonic acid as catalysts, and methanol, ethanol or toluene as solvents, or under solvent

• -free conditions. Although some new metal or Brønsted acid catalysts have been reported in the last few years, the main innovations can be found in the use of organic catalysts, enzymes, and compartmentations. A few reports on the in situ generation of reactants and on the reaction conducted under flow

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• bearing electron-donating or halogen groups. This practical method is characterised by atom economy and offers a direct route to the introduction of an aryl moiety into the C(5)-position of deazaalloxazines, thereby generating novel catalysts for photoredox catalysis without the need for subsequent

• vary from low to moderate, the reaction starts from commercially available substances and leads to valuable compounds. The procedure is low cost and operationally easy with no need for further purification and opens a new route to the synthesis of powerful, phoredox, flavin-like catalysts, as well as

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• from ligands for catalysts [2], through pharmaceuticals [3], to organic semiconductors [4][5]. Despite their fundamental and applicative importance to many fields, the vast chemical space of PASs has remained largely unexplored. As a result, the relationships between the arrangement and composition of

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• ; enantioselectivity; halogenation; lactones; organocatalysis; Introduction Catalytic asymmetric halolactonizations of alkenoic acids are powerful methods for the preparation of important chiral lactones in enantioenriched forms [1][2][3][4][5][6][7][8][9][10][11]. A wide variety of chiral catalysts have been applied

• remained a formidable challenge in the field of catalytic asymmetric synthesis (Scheme 1b) [23][24][25]. To address this limitation, we have investigated the use of BINOL-derived chiral bifunctional sulfide catalysts, which were developed by our group [10], in asymmetric bromolactonizations of α

• bifunctional sulfide (S)-1 [26][27][28][29][30][31]. To further demonstrate the utility of our chiral bifunctional sulfide catalysts in challenging halolactonizations, we next turned our attention to the asymmetric bromolactonizations of 5-hexenoic acid derivatives 2 for the synthesis of optically active δ

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• through directed evolution [11]. P450 catalysis during the oxidation phase enabled the total synthesis of mitrephorone A [12], chevalone A [13], polysin [14], excolide B [15], and gedunin [16]. Fe(II)/2OG-dependent dioxygenases, such as FtmOx1, were employed as versatile catalysts in the synthesis of 13

• novel paradigm for exploiting the inherent specificity and efficiency of enzymatic catalysts within synthetic sequences. The integration of designed substrate analogs that can be transformed by promiscuous enzymes provides a versatile synthetic platform towards natural products and their derivatives. In

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• oxidants in combination with transition-metal catalysts. Metal-free methods employ chlorodimethylsulfonium compounds as the reactive species and have gained great popularity under the name Swern oxidation or the Corey–Kim oxidation [11]. Hypervalent iodine compounds have also been studied and are well

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• ] and experimentally validated their approach using six pharmaceutical intermediates from medicinal chemistry programs. In the article, they state that ”Iridium catalysts ligated by bipyridine ligands catalyze the borylation of the aryl C–H bonds that are most acidic and least sterically hindered…”[45

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• involving the use of Sc(OTf)3 and TsOH as the catalysts were tested on a broad substrate scope, and prevalence of the first method was clearly demonstrated. Furthermore, the scope and limitations of the procedure were established. A model 790-member library was obtained with 85% synthesis success rate

• -house experience on isonitrile-based parallel reactions, electron-poor (hetero)aromatic isonitriles were not included in the study). According to Boltjes and Dömling, the following three catalysts were applied most often to promote the title reaction [21]: Sc(OTf)3 (described first in the original work

• space were found in the ChEMBL database, and some of them had high potency against various biological targets. Marketed drugs comprising imidazo[1,2-a]azine scaffolds. Yields of library members 4 synthesized using both Sc(OTf)3 and TsOH as the catalysts. Amino heterocycles 1{1–27} demonstrating poor

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• ), the charge for screening was set to 2.0 F mol−1 for rapid evaluation, and several cathode catalysts were examined. When Pd/C was used as the cathode, the reaction did not proceed (Table 3, entry 1). The desired reduction proceeded with Ru/C and 5a was obtained in 79% of current efficiency (Table 3

• F mol−1 of electricity should be required ideally to reduce quinoline (6a) to 1,2,3,4-tetrahydroquinoline (7a), 4.0 F mol−1 of electricity was applied for the reactions. Pd/C, Ir/C, Ru/C, and Pt/C were used as cathode catalysts, and 3–5% yields of 7a were obtained by the use of each catalyst (Table

•  5, entries 1–4). We chose Pt/C, one of the most common catalysts used in fuel-cell reactors, and increased the charge to complete the reaction. With 50 F mol−1 of electricity, 6a was completely consumed and 7a was obtained in 96% yield (Table 5, entry 5). However, the electrochemical reaction of 6a

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• authors displayed the stability of the secondary benzyl fluoride 9 to various SNAr conditions. While these methods demonstrate excellent application of palladium catalysts to perform benzylic fluorinations, the need to install a directing group can limit substrate scope. Therefore, methods that can

• -methylquinoline derivatives could be fluorinated in yields of up to 70%. In 2013, Groves and co-workers reported the use of manganese salen and manganese porphyrin catalysts in the preparation of a range of secondary benzyl fluorides via C–H fluorination (Figure 31) [80]. Substrates bearing electron-withdrawing

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• -covalent catalysis via bifunctional hydrogen-bonding organocatalysts. The C-4 nucleophilicity of pyrazolin-5-ones was also explored in enantioselective reactions with α,β-unsaturated carbonyl compounds through covalent catalysis with chiral amine-based catalysts; however, it has achieved limited success

• metal catalytic conditions. In continuation of our work in the field of organocatalysis [26][27][28][29], herein, we present the Michael addition reaction of 4-unsubstituted pyrazolin-5-ones with arylidene/heteroarylideneacetones using cinchona alkaloid-derived primary amine catalysts. The developed

• primary amine catalysts (see Table S1 in Supporting Information File 1) in toluene at room temperature (30–32 °C). When the test reaction was conducted in the presence of 15 mol % of 9-amino-9-deoxy-epicinchonidine (I) as catalyst [30] for 12 h and treated with Ac2O followed by DABCO, the reaction gave

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• ][25][26][27][28][29][30][31]. Such oxidative coupling strategies of two inherently nucleophilic species allow for the direct utilization of simple starting materials in an efficient manner and especially the use of quaternary ammonium iodides as redox active catalysts has emerged as a powerful

• easily available and cheapest nucleophilic N3 source (for other remarkable approaches using alternative catalysts and oxidants see references [24][25][26]). In addition to the racemic approach, they also showed that this reaction can be rendered enantioselective by using advanced Maruoka-type quaternary

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• , Iran 10.3762/bjoc.20.134 Abstract We herein report the asymmetric organocatalytic addition of azlactones to allenoates. Upon using chiral quaternary ammonium salt catalysts, i.e., Maruoka’s binaphthyl-based spirocyclic ammonium salts, the addition of various azlactones to allenoates proceeds in a β

• [29] as well as α-amino acid-based thiazolones [30] have successfully been used for asymmetric β-selective additions to allenoates when using chiral ammonium salt catalysts or chiral organobase catalysts. However, to the best of our knowledge the β-selective asymmetric addition of azlactones 1 to

• these catalysts (Table 1, entries 1–4, other cinchona alkaloid-based ammonium salt derivatives as well as free base cinchona alkaloids were tested too but did not allow for any improvement). Using the established and commercially available Maruoka catalysts B1 and B2 [39] next turned out to be more

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• efficiency. Results and Discussion Our study of this new electrophotochemical metal-catalyzed decarboxylative cyanation commenced with the evaluation of various combinations of Ce and Cu catalysts. A simple undivided cell using a carbon felt, inexpensive and practical porous material as the anode, and a Pt

• success of this transformation (Table 1, entries 6–9). We also tested other photoredox catalysts that are capable of driving the oxidative decarboxylation, only Fukuzumi catalyst [47] was able to deliver the product with a meaningful yield (Table 1, entry 10). The scope of this transformation was next

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• acceptable to high yields. Mild reaction conditions, no requirement of metal catalysts, operational simplicity and the potential for scale-up production are some of the highlighted advantages of this transformation. Keywords: aniline; (E)-2-arylidene-3-cyclohexenone; imine condensation; isoaromatization

• -benzylidenecyclohex-3-en-1-one (2a) and 4-methoxybenzylamine (3a) as starting materials to investigate the feasibility and efficiency of the reaction (Table 1). Initially, the reaction was conducted in the presence of 2.0 equiv of 3a in toluene at 60 °C without any addition of catalysts or additives. To our delight

• , 2a could be fully converted and the 2-benzylaniline 4aa was obtained in 52% yield after 46 h (Table 1, entry 1). Some commonly used acid catalysts were tested, however, neither Brønsted acids such as AcOH and TsOH, nor Lewis acids such as FeCl3 and BF3·Et2O, showed a promoting effect on the aimed

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• of cationic monovalent halogen-bond donors 37–40 with chloride as the imidazolium iodide is a well-established core of halogen-bonding catalysts [34][35] (Scheme 3). In general, we observed that more exergonic association of the halogen-bond donors with chloride were associated with closer X---Cl

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• development of chiral hypervalent iodines by Wirth, Kita, Ishihara, Muñiz, and many others, have firmly established these reagents as useful catalysts for a wide variety of chemical transformations [6][7][8][9][10][11][12][13][14][15][16][17]. A number of features, including low toxicity, high stability, ease

• of handling, and versatile reactivity, etc. render these catalysts highly attractive for adoption in organic synthesis. In particular, the field of olefin difunctionalization, known for its rapid assembly of molecular complexity, has been a fertile ground for innovation for hypervalent iodine

• alkenes regioselectively to furnish their respective oxazoline regioisomer (Scheme 1d). Herein, we report that lithium salts such as LiBF4 or LiPF6, which are often used in lithium-ion batteries, can be used to activate hypervalent iodine catalysts to enable olefin oxyamination reactions with simple

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• KSF clays as recyclable and heterogeneous catalysts to catalyze the Cannizzaro reaction by 1,4-diazabicyclo[2.2.2]octane under microwave irradiation and solvent-free conditions giving the products in excellent yields within seconds. The solid clay applied in the first cycle can be recovered and reused

• different phase-transfer reagents and catalysts such as benzyltriethylammonium chloride, tetrabutylammonium bromide and many others have had profound impacts on the Cannizzaro reaction. Entezari and Shameli [27] studied the effect of an ultrasonic wave on the Cannizzaro reaction catalyzed by a phase

• numerous modified techniques, which established the greener side of the reaction. The use of Lewis acid catalysis in this regard [34][35][36][37][38][39] played a significant role, which also suppressed the epimerization in the case of chiral molecules. Among the various Lewis acid catalysts such as

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• photocatalysts, transition-metal photoredox catalysts, and metallaphotocatalysts to produce acyl and alkyl radicals driven by visible light. Keywords: acyl radical; alkyl radical; sustainable catalysis; visible light; Introduction The growing awareness of the necessity for sustainable developments has been

• of novel synthetic strategies. It has expanded the scope of available synthetic methods and contributed to the synthesis of complex molecules with high efficiency and selectivity. Ongoing research in this field continues to explore new catalysts, photosensitizers, and reaction mechanisms to further

• side product 85 was transformed into the aldehyde by acidic workup. Conclusion The techniques, catalysts, and mechanistic analyses of homogeneous catalytic deoxygenation processes for high-value products have advanced significantly over the last few years. This review presents an extensive overview of

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• . Therefore, alternative procedures for homo-coupling reactions using other transition-metal catalysts such as palladium, nickel, manganese, and iron have been developed [5][6][7][8][9][10][11][12][13]. In recent years, transition-metal-free coupling reactions have also been developed for environmentally

• reaction mixture (Table 1, entry 10). Next, we investigated various Rh catalysts and solvents, and the results are summarized in Table 2. All Rh catalysts that were examined in this reaction gave the product in good yields, although in the absence of a Rh catalyst the reaction failed as shown in Table 2

• Grignard reagents. Rh-catalyzed one-pot Ullmann-type reaction with bromobenzene under optimized reaction conditions. Synthesis of compound 10n as a candidate for an integrin inhibitor. Examination of various alkyl halides as an oxidant. Examination of various Rh catalysts and solvents. Supporting