First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• as ligands in organometallic catalysts [9] and as versatile organocatalysts [10] in a very wide range of organic reactions such as classical benzoin condensation, transesterification, acylation, Knoevenagel reaction, Claisen condensation etc. The electrochemical generation of carbenes from ILs avoids

• atom is reversed (umpolung) from electrophilic to nucleophilic (Scheme 3). This approach can be exploited in many organic reactions, such as: the benzoin condensation [16][17], esterification and amidation of benzaldehydes and cinnamaldehydes [18][19], synthesis of γ-butyrolactones [20], synthesis of

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• . Jones disclosed an original synthesis of 2-hydroxypyrazines involving a double condensation between 1,2-dicarbonyls and α-aminoamides upon treatment with sodium hydroxide at low temperature. This discovery turned out to be of importance as even today there are no simple alternatives to this preparation

• occurrence of 3,5-substituted-2-hydroxypyrazine as the major reaction product. Keywords: α-aminoamide; condensation; hydroxypyrazine; methylglyoxal; phenylglyoxal; Introduction In a recent report [1], the many ways a pyrazine nucleus is able to interact with proteins were reviewed. In this text, it was

• reactions to generate libraries of pyrazine derivatives [3][4]. In any case, as depicted in Scheme 1, Reuben G. Jones, working in 1949 in Eli Lilly’s Indianapolis research facilities, reported a sodium hydroxide-promoted condensation between 1,2-dicarbonyls 1 and the free base of α-aminoamides 2 to give the

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• ) condensation of ʟ-tryptophan (1) with different aldehydes (a–e) in dry DCM at room temperature yielded tetrahydro-β-carboline derivatives 2a–e, which were then oxidized with KMnO4 in anhydrous DMF for 45 minutes to yield β-carboline derivatives 3a–e. It was encouraging to observe that the P-S condensation with

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• ]. In the same year, they also realized the synthesis of 2-phenyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxide (55) in 75% yield by heating at 190–200 °C and in 47% yield by DCC condensation of compound 54 – the oxygen analogue of 2-aminobenzyl(phenyl)dithiophosphinic acid 58. The cyclodehydration

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• includes eight steps starting from the condensation of pyruvate and ᴅ-glyceraldehyde 3-phosphate (G3P) [13][14] (Figure 1a). Due to these lengthy biosynthetic steps as well as complex metabolic regulations and extensive cofactor requirements, several groups have engineered elegant bypass pathways to

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• different kinds of aromatic aldehydes and 5-arylidene-1,3-dimethylbarbituric acids. 5-Arylidene-1,3-dimethylbarbituric acids could be easily generated through Knoevenagel condensation of aromatic aldehydes and 1,3-dimethylbarbituric acid under the catalysis of Lewis acid. We envisioned whether the desired

• 3-substituted indole, which undergoes dehydration to form the key intermediate indole-based ortho-quinodimethanes (o-QDMs, A). In the meantime, the cyclic 1,3-diones and aromatic aldehyde undergo Knoevenagel condensation to afford the different kinds of dienophiles. Subsequently, the Diels–Alder

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• scalable (i.e., a maximum of 15% by 1H NMR). Finally, due to the concentration of α-iodopropiophenone (6) employed, we detected the formation of a byproduct in the last stages of the optimization, namely the condensation of the desired product with α-propiophenone in the form of an enol ether. Once this

• perfluoroalkylating reagent that participated in such condensation (around 30%), giving us the final yields of perfluoroalkylating reagents 1a–c displayed in Scheme 3. Afterward, to show the practicality of application of these reagents in industry, we proceeded to scale up their synthesis in gram-scale

Continuous flow synthesis of azobenzenes via Baeyer–Mills reaction

• Jan H. Griwatz,
• Anne Kunz and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2022, 18, 781–787, doi:10.3762/bjoc.18.78

• based on the condensation of nitrosobenzenes with anilines (Scheme 1). This so-called Baeyer–Mills reaction, which was first published by Baeyer in 1874 and further investigated by Mills, proceeds best for electron-rich anilines with electron-poor nitrosobenzenes. The reactivity can be rationalized by

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• ” and only “slightly fruity” [9]. Kappe and co-workers disclosed an access to both odorants in a two-step synthesis (Scheme 1) [24]. In the first step, 4-aryl-3-buten-2-ones 3 and 4 are prepared via aldol condensation of the corresponding aldehydes 1 and 2 and acetone in 78–90% yield with a productivity

• . For compound 6, both individual steps were combined for a two-step aldol condensation/hydrogenation flow sequence providing raspberry ketone methyl ether (6) on a gram scale in 75% overall yield. Interestingly, also alternative flow protocols for the synthesis of 4-aryl-3-buten-2-ones 3 and 4 were

• formation of hydrazone 28. As one equivalent of water is formed in this condensation process, which is detrimental for the subsequent Shapiro reaction, water is continuously removed by in-line separation of the reaction mixture using a PTFE-membrane separator. The organic layer is then mixed with a solution

Identification of the new prenyltransferase Ubi-297 from marine bacteria and elucidation of its substrate specificity

• Jamshid Amiri Moghaddam,
• Huijuan Guo,
• Karsten Willing,
• Thomas Wichard and
• Christine Beemelmanns

Beilstein J. Org. Chem. 2022, 18, 722–731, doi:10.3762/bjoc.18.72

• -2-naphthoic acid (DHNA) via an intermediate decarboxylative coupling step yielding demethylmenaquinone (DMK) [9]. In contrast, COX10 and chlorophyll synthases are known to fuse prenyl or phytyl tails to porphyrins as acceptors, while homogentisate prenyltransferases catalyze the condensation of

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• molecules through π–π stacking with the hydrophobic aromatic wall of the host. Finally, the boat was investigated as a catalyst for the Knoevenagel condensation reaction (Figure 2) of a series of aromatic aldehydes with 1,3-dimethylbarbituric acid and Meldrum’s acid in aqueous media. One of the primary

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• -phenylenediamine. The general method for the preparation of the corresponding quinoxalines on the basis of the aforementioned condensation was implemented. It was demonstrated that the studied photoreaction does not depend on the type of pyrazole bridge. The structures of three of synthesized products were

• -hydroxy-1,2-diketones 2 is the condensation with 1,2-phenylenediamine resulting in the formation of fused quinoxalines 3 (Scheme 1A) [22]. Another variant of similar catching reaction is reduction by NaBH3CN with the formation of diols 4 (Scheme 1A) [23]. Thus, the introduction of additional reagents

• the conversion of previously obtained unstable α-hydroxy-1,2-diketone 14a–l into the corresponding quinoxalines 15a–l (Scheme 5). As it was shown earlier, acetic acid is the optimal solvent for the studied compounds and this solvent is also widely used for the condensation of α-diketones with 1,2

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• 2004, Takata and co-workers synthesized thiazolium-based chiral [2]rotaxanes as catalysts for the asymmetric benzoin condensation [56][57]. For the synthesis of the rotaxane, ammonium salts 34a/b and the BINOL-based macrocycle (R)-12 were interlocked via tributylphosphine-catalyzed acylative end

• , rotaxane (R)-38 was obtained in 35% overall yield (see Figure 8b). These rotaxanes where then used as catalysts for the asymmetric benzoin condensation of benzaldehyde (39). The best yield (90%) could be generated at 0 °C in methanol with 10 mol % of catalyst (R)-35a, albeit with a low stereoselectivity

• featuring BINOL-based [2]rotaxane side chains. Synthesis of Takata´s chiral thiazolium [2]rotaxanes (R)-35a/b and (R)-38. Results for the asymmetric benzoin condensation of benzaldehyde (39) with catalysts (R)-35a/b and (R)-38. Synthesis of Takata´s pyridine-based [2]rotaxane (R)-42. The asymmetric

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• readily incorporated by both homo and hetero [1 + 1] macrocyclic condensation of bisamine and bisisothiocyanate fragments. With the easy synthesis, gram-scale of macrocycle products can be readily obtained. These chiral macrocycles were applied in catalyzing bioinspired decarboxylative Mannich reactions

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• Michael addition with another molecule of 3-phenacylidieneoxindole to yield intermediate B. Finally, an intramolecular aldol condensation takes place between the carbanion and the carbonyl group of intermediate B towards the formation of the dispirocyclopentanebisoxindole derivative. To support the

• cyclization of two molecules of 3-phenacylideneoxindoles. In this reaction tosylhydrazine serves as reducing agent to reduce one molecule of 3-phenacylideneoxindole to 3-phenacylindolinone which, under base-catalyzed conditions, involves a sequential Michael addition/intramolecular aldol condensation with

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• mol % bismuth(III) triflate catalyst and compound 73 was obtained in 75% yield (Scheme 23). Carbonyl condensation Another possible derivatization involves transformations at the carbonyl groups in menadione that can be achieved through the addition of nucleophiles to the carbonyl group at position C-4

• . In this context, Nagaraja and co-workers reported the condensation of menadione (10) under different mild conditions, during the development of analytical methods for determining 10 in pharmaceutical preparations [124]. In method A, menadione (10) was treated with concentrated sulfuric acid and

• resorcinol (74), generating the intermediate 75 which underwent intramolecular condensation, to furnish 76. In method B, menadione (10) was treated with 3-methyl-2-benzothiazolinone hydrazone (77) in alkaline medium forming diazocompounds as addition products, which spontaneously lose N2 to form product 78

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• urea derivatives with β,γ-unsaturated ketoesters and subsequent intramolecular condensation could lead to 5-unsubstituted DHPM derivatives. β,γ-Unsaturated ketoester 7, derived from benzaldehyde and pyruvic acid [40], on exposure to ʟ-(+)-tartaric acid–N,N-dimethylurea (DMU) melt underwent smooth

A Se···O bonding catalysis approach to the synthesis of calix[4]pyrroles

• Qingzhe Tong,
• Zhiguo Zhao and
• Yao Wang

Beilstein J. Org. Chem. 2022, 18, 325–330, doi:10.3762/bjoc.18.36

• ]pyrrole derivatives. The Se···O bonding interactions between selenide catalysts and ketones gave rise to the catalytic activity in the condensation reactions between pyrrole and ketones, leading to the generation of calix[4]pyrrole derivatives in moderate to high yields. This chalcogen bonding catalysis

• approach was efficient since only 5 mol % catalyst loading was used to promote the consecutive condensation processes while the reactions could be carried out at room temperature, thus highlighting the potential of this type of nonclassical interactions in catalyzing relative complex transformations

• between ketones and pyrrole might take place to give calix[4]pyrrole derivatives under catalysis of a selenide catalyst. In the absence of a catalyst, no reaction took place. Indeed, even in presence of 5 mol % representative catalyst Ch1 [44], the condensation reaction between acetone and pyrrole worked

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• cyclization leading to the formation of polycyclic azepino[5,4,3-cd]indoles. Synthesis of azepino[3,4,5-cd]indoles via iridium-catalyzed asymmetric [4 + 3] cycloaddition of racemic 4-indolyl allylic alcohols with azomethine ylides. Aldimine condensation/1,6-hydride transfer/Mannich-type cyclization cascade of

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• from aldehydes, a carboxylic acid, and a isonitrile as the three components [23]. The sequences of Passerini reactions, followed by post-condensation reactions, constitute useful synthetic methods in the preparation of structurally diverse heterocyclic compounds [24][25][26][27][28][29]. The aza-Wittig

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• regioisomeric 1,2-oxazole derivatives. Accordingly, the synthetic route starts from the condensation of 1,3-diketones with N,N-dimethylformamide dimethylacetal to form β-enamino ketoester. The latter undergoes a subsequent cycloaddition reaction with hydroxylamine to form regioisomerically substituted 1,2

• 7.80 ppm) and the dimethylamino nitrogen (δ −269.7 ppm) was observed, thus allowing to prove the formation of β-enamino ketoester. Analysis of the possible resulting reaction showed that the condensation reaction between β-enamino ketoester precursors 3a–h and hydroxylamine could lead to the formation

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• synthesis of oxazoline derivatives [11][12]. They mainly include (1) cyclization of 2-amidoethyl halides or sulfonates, which are prepared from carboxylic acid derivatives and vicinal amino alcohols [8][9][10] (Scheme 1a); (2) direct condensation of carboxylic acid derivatives or nitriles with vicinal amino

• alcohols [13][14][15] (Scheme 1a); (3) oxidative condensation of aldehydes with vicinal amino alcohols [16] (Scheme 1b); (4) cyclization of N-allylamides in the presence of electrophilic reagents or radical initiators or catalysts [17] (Scheme 1c); (5) direct synthesis from alkenes and amides or nitriles

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• ) and PGE2 in alveolar macrophages. Then, oximes 46a,b and 48b were obtained by condensation of 45a,b and 47b with hydroxylamine, respectively. Biological results indicated that 47b significantly attenuated the release of inflammatory mediators (NO, TNF-α, and MMP-9) in a concentration-dependent manner

• + was developed by Gates and Newhall in 1948 [107]. Land and co-workers demonstrated that cyanomethyl derivatives of ortho-quinones undergo facile tautomerism to para-quinomethanes [108]. Villemin and co-workers summarized these reactions, which were expanded to several other condensation products with

• methylene acid compounds [109]. These authors developed two methods (A and B) to prepare 2-hydroxynaphthoquinomethanes 62 with diverse structures by condensation of 18 with active methylene compounds (Scheme 18). Method A involves the reaction promoted by sodium hydroxide in an ethanol/water mixture at 40

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• afforded the products in excellent yields. The authors also conducted various experimental and theoretical studies to analyze the reaction mechanism. The proposed mechanism begins with the oxidative dehydrogenation of the alcohol to afford the aldehyde which undergoes condensation with ammonia to give the

Study on the interactions between melamine-cored Schiff bases with cucurbit[n]urils of different sizes and its application in detecting silver ions

• Jun-Xian Gou,
• Yang Luo,
• Xi-Nan Yang,
• Wei Zhang,
• Ji-Hong Lu,
• Zhu Tao and
• Xin Xiao

Beilstein J. Org. Chem. 2021, 17, 2950–2958, doi:10.3762/bjoc.17.204

• : cucurbiturils; melamine; Schiff base; silver ion; Introduction Schiff bases [1] are usually synthesized by the condensation of amines and active carbonyl compounds, endowing them both nitrogen and oxygen donor atoms [2][3][4][5]. Schiff bases are not only easy to coordinate with various transition metal ions