Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• be carried out in a one-pot fashion with comparable results and without significant variation from the two-step procedure. Utilization of the Povarov reaction and subsequent oxidation by DDQ was also done by Wang et al. in 2020 [54]. In situ-formed imines from anilines 91 and benzaldehydes 92 were

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• catalyst tolerated all p-, m-, o-Cl-substituted benzaldehydes in terms of both reactivity and selectivity, affording the essentially same results as benzaldehyde (2b–d). Other electron-deficient substituents CF3 (2e) and Br (2f) did not adversely affect the reaction. However, electron-donating substituents

• benzaldehydes, which may be attributable to that they have smaller steric demands in the vicinity of the carbonyl carbon atom than benzaldehyde. Importantly, we did not observe the corresponding homopropargylic alcohols [51] in all cases. Since this work is the first asymmetric catalysis study of isomerically

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• 18). Reaction scope We then used optimized reaction conditions from Table 1, entry 16 (method A) and 12 (method B) to further explore the scope of the reaction (Scheme 2). By employing various EWG/EDG-substituted benzaldehydes and urea/thiourea/selenourea we synthesized novel Biginelli products 2a–q

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

• using 30 equiv of AcOH in DMA, with no damage of DNA observed. The GBB reaction, under these mild conditions, demonstrated a wide range of scope. Different aldehydes were tested: benzaldehydes with different substituents, heteroaromatic and bicyclic aromatic aldehydes, all giving good results. Only

• elimination of III, underwent intramolecular cyclization to deliver the desired products 85. The scope of reaction showed that higher yield (57–90%) of 85 were obtained when benzaldehydes 83 were equipped with electron-donating groups (R1) and when bulky groups, such as 1-adamantyl or t-Bu (R4), were

• products 109, formally derived from a GBB reaction with aromatic isocyanides and benzaldehydes. The same approach was used by Jalani and Jeong [70] where p-TsOH served as the catalyst for the one-pot reaction. A library of 21 examples of 109 were produced in 41–78% yields. Various functional groups were

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

• isolated in a high yield of 84% with reisolation of the 5-(2-iodophenyl)-1H-tetrazole (6) in 90% yield. Other para-halogenated benzaldehydes 4b–f were isolated in good yields of up to 88%. ortho-Substitution led to a lower yield of the iodinated product 4g (43%) compared to the para-iodinated analogues 4d

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• reactions in hands, we next evaluated the substrate scope by synthesizing 11 derivatives (Scheme 4) using nine benzaldehydes 1, two isonitriles or ethyl isocyanoacetate 4, allylamine hydrochloride (2), and trimethylsilyl azide (3) for the initial Ugi-azide reaction. Among them, products 6a and 6b from the

•  5) using seven benzaldehydes 1, two isonitriles 4, and allylamine hydrochloride (2) with trimethylsilyl azide (3) for the Ugi-azide reaction. The N-alkylations were conducted using benzyl bromide and iodomethane, respectively. The final products 8b–j were obtained in 66–74% yields. To evaluate the

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• Ar and CF3 groups can localize the negative charge and also provide steric effects to afford stereoselective cycloaddition products with 3:1 to 6:1 dr. The steric hindrance also prevents products 9 from undergoing a second cycloaddition. The control reactions of methyl ketone or benzaldehydes gave

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• appearance of a solid–liquid biphasic mixture as the components of the DES are water-soluble. A large volume of water should be used since otherwise some DES traces are present in the NMR spectrum of the precipitate. Benzaldehydes having electron-donating or electron-withdrawing groups were studied as well

• benzaldehydes with electron-donating or electron-withdrawing groups could be used as substrates. The method is fast, easy, catalyst-free, and sustainable as no classical organic solvents were used. The synthesized derivatives were studied for their antioxidant activities and as expected, all compounds with a

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• range of substituents at the aromatic cores was tolerant to the reaction conditions, and the yields of the desired products 4 remain moderate to good (Scheme 2). In particular, the use of starting benzaldehydes 2 containing electron-donating groups leads to the desired products 4e–g,i–k in much higher

• 2-(5-methylfuran-2-yl)ethylamine and aromatic aldehydes. The use of starting benzaldehydes containing electron-donating groups leads to the desired products in much higher yields than with aldehydes containing electron-withdrawing moieties. The availability of the starting materials, mild reaction

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• structure raised the mixing efficiency of a gas–liquid reaction system, and it effectively accelerated the aerobic oxidation of benzyl alcohols to benzaldehydes under continuous-flow conditions. This reactor is a promising device for streamlining aerobic oxidation with high process safety because it is a

• closed system. Keywords: aerobic oxidation; benzaldehydes; benzyl alcohols; homogeneous catalyst; honeycomb reactor; Introduction Oxidation plays a key role in synthesizing highly functionalized molecules [1][2]. While Jones oxidation [3] and oxidation using KMnO4 [4] are classical and powerful methods

• ], and its screening results can be transferred to obtain a wide variety of benzaldehydes from benzyl alcohols. The screening was conducted under batch conditions. Toward its application to continuous-flow synthesis, we considered the description of the reaction mixture as well as the reaction rate

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• described the selective palladium-catalyzed ortho-2,2,2-trifluoroethoxylation of a series of benzaldehydes (Scheme 22, 35 examples) using the amino acid ʟ-valine in the presence of K2S2O8 and TFA at 80 °C [153]. This reaction proved to be highly tolerant to various substituents including a CF3 group at the

• ortho-, meta- and para-positions (48m, 48j, and 48f, respectively), halogens (48d, 48h, and 48l), an ester moiety (48e and 48i), and a methoxy group (48c). Note that even di- and trisubstituted benzaldehydes 47n–q were smoothly functionalized under these conditions. The authors also suggested a

• and Wang used a similar approach for the 2,2,2-trifluoroethoxylation of benzaldehydes under palladium catalysis using the amino acid 51 as organic catalyst in the presence of the fluoropyridinium salt 52 (19 examples, up to 88% yield, Scheme 23) [183]. Pleasingly, the methodology was extended to the

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• University, Kaliningrad 236016, Russian Federation 10.3762/bjoc.18.175 Abstract The previously described α-acetyl-α-diazomethanesulfonamide was employed in a three-component reaction with azide-containing benzaldehydes and propargylamines. Besides the initial formation of the triazole core, the reaction

• benzaldehydes and propargylamines. Besides the initial formation of the triazole core, the reaction proceeded further, in uncatalyzed fashion at room temperature and yielded structurally intriguing bistriazoles whose structure was unequivocally confirmed by single-crystal X-ray analysis. Compounds are non

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• bromides from one starting aryl aldehyde. Diethyl phosphite was allowed to react with appropriately substituted benzaldehydes in THF for 48 hours at 25 °C to afford diethyl (hydroxy(aryl)methyl)phosphonates 1, which were detected by 31P NMR spectroscopy in THF (21.4 ppm for 1a, 21.0 ppm for 1b, and 21.5

• ppm for 1c). Further, reaction mixtures with compounds 1 were treated with SOCl2 for 3–4 h at 0 °C and converted to chloro derivatives 2. In the next step, compounds 2 and starting substituted benzaldehydes were subsequently treated with 2 equiv of potassium tert-butoxide in THF for 18 hours at room

• transition metal-catalyzed cross-coupling reactions broadly used for the preparation of different diarylacetylenes and, rarely, bis(chlorophenyl)acetylenes. Next, starting substituted benzaldehydes were treated with an excess of SOCl2 for 24 h at 25 °C. Corresponding substituted benzal chlorides 4 were

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

• 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

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• reacted smoothly with various substituted aldehydes (containing a bromo, fluoro, hydroxy, chloro, ethyl, or methyl group) affording the corresponding products 5b–g with good to excellent yields. Also, 3,4,5-trimethoxy-, 2,4,6-trimethyl-, anthracene-9-yl-, and naphthalene-1-yl-substituted benzaldehydes

• and fluoro-substituted anthranilamides and aldehydes (Figure 4). Initially, 2-amino-5-fluorobenzamide was reacted with various benzaldehydes having bromo, ethyl, methyl, styryl, and cyclohexyl groups to produce the respective cyclized products 6b–f with good to excellent yields. Similarly, biphenyl

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• well as by Sm(OTf)3-catalyzed stereoselective [3 + 2] cycloaddition of bis-silyldienediolate and imines, in turn synthesized from anthranylamides and benzaldehydes [32]. A promising approach to the synthesis of 2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one derivatives substituted at the pyrrolidine

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• building blocks (ring-substituted N-ethoxycarbonyl phenethylamines A and ω-methoxystyrenes B) were, if not commercially available, prepared from appropriately substituted benzaldehydes (see Supporting Information File 1). For the ω-methoxystyrenes, phenolic groups in the benzaldehydes were protected using

• ethyl chloroformate/Et3N, followed by Wittig olefination with an ylide generated from (methoxymethyl)triphenylphosphonium chloride and LDA to give the enol ethers as E/Z mixtures. N-Phenethyl carbamates were obtained from benzaldehydes via Henry reaction with nitromethane, followed by zinc dust

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• nobilone (25) in 8 steps in an overall yield of 2%. This protocol allows the synthesis of variously substituted fluorenones, since the required 2-(aminomethyl)biphenyls are readily available from commercially available building blocks (substituted benzonitriles or benzaldehydes, areneboronic acids) via

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• example, when benzaldehydes substituted with fluorine or chlorine in the para-position were employed in catalytic reaction with anthranilamide (1a), the corresponding derivatives 3i,j were isolated in 58 and 69% yield, respectively. The rates of enantioselectivity for both reactions were lower and

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• (III)-catalyzed intramolecular cyclization of O-acetyloximes (Figure 2, reaction 1). However, this transformation was limited to ketoximes and yielded only 6-substituted phenanthridines [7]. Applying photochemical conditions, Rodrıguez and Walton were able to use benzaldehydes utilizing a similar

• intramolecular cyclization of O-acetyloximes to afford phenanthridines. (Figure 2, reaction 2) [8][9]. For these transformations, the reaction is thought to go via the transient iminyl radical [10]. More recently, Yu has reported the use of in situ-derived O-acyl oximes from benzaldehydes that when subjected to

• radicals. Two possible mechanistic routes and intermediates in the synthesis of phenanthridines. Previous unexpected synthesis of the phenanthridine framework. Synthesis of biaryl benzaldehydes. Synthesis of biaryl oximes. Synthesis of phenanthridines. Reagents and conditions (i) UV irradiation (450 W

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• ortho-acetal diarylmethanols. Lewis acid-mediated regioselective cyclization of asymmetric diarylmethine dipivalates and diarylmethine diols. BF3·OEt2/CF3SO3H-mediated cyclodehydration reactions of 2-(arylmethyl)benzaldehydes and 2-(arylmethyl)benzoic acids. Synthesis of 2,3,6,7

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• paroxetine (81), loratadine (82), and suvorexant (83) was achieved in moderate yields (Scheme 29C). In 2019, Han and collaborators reported a biomimetic Fe-catalyzed aerobic oxidation of methylarenes to benzaldehydes by using inexpensive and nontoxic reactants (Scheme 30A and B) [162]. The method was

Cerium-photocatalyzed aerobic oxidation of benzylic alcohols to aldehydes and ketones

• Girish Suresh Yedase,
• Sumit Kumar,
• Jessica Stahl,
• Burkhard König and
• Veera Reddy Yatham

Beilstein J. Org. Chem. 2021, 17, 1727–1732, doi:10.3762/bjoc.17.121

• the corresponding halo-substituted benzaldehydes 2a–d in good yields. The oxidation of simple benzyl alcohol (1e) under our reaction conditions gave benzaldehyde (2e) in 55% yield. A variety of electron-donating para-substituted benzyl alcohols (1f–h) gave lower isolated yields of the corresponding

• benzaldehydes 2f–h. Our methodology tolerates a variety of functional groups containing benzylic alcohols such as -OH (1h), -CN (1i), -NO2 (1j), methyl ester (1k), and benzyloxy (1v) to produce the corresponding aldehydes (2h–k and 2v) in moderate yields. Next, electronically different ortho-substituted

• ) benzylic alcohols yielded the corresponding benzaldehydes 2o and 2p in moderate yields and to our surprise we did not observe any oxidation of the methyl or methoxy groups via hydrogen atom transfer processes [57]. Interestingly, we found that a variety of ortho-phenoxy-substituted benzylic alcohols (1q

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• ., benzaldehydes) and low-molecular-weight enolate nucleophiles, therefore, temperature regulation is vital for selectivity. This requirement for strict temperature control makes aldol reactions highly suited to flow processing conditions. In 2008, Tanaka et al. [96] disclosed several examples of aldol reaction in

• . In 2008, the group of Sartori developed a flow setup for nitroaldol condensations of different benzaldehydes exploiting a silica-supported amine (KG-60-NH2) as a heterogeneous catalyst (Scheme 21) [133]. Secondary and tertiary amine-supported catalysts were also investigated, although they were found