Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• condensation by introducing additional functional groups into the amine moiety (Figure 3). Substituted arylamines bearing alcohol (3ae), phenol (3ad), alkene (3bi), dimethyl acetal (3bj) functionality can be accessed in good yields. Reaction of 1,3-diketone 1a with a non-amidine type heterocyclic amine, 3

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• catalysis not only enables the synthesis of alkynones, but also facilitates the introduction of protected alkynal moieties, which can be converted to pyrazoles in a one-pot fashion. Sonogashira coupling is particularly well-suited for this purpose. The alkynylation of propynal diethyl acetal (140) and

• (hetero)aryl iodides gives rise to 3-arylalkynyl acetals 142. Since 3-arylpropynals are sensitive to oligo- and polymerization, it proved useful to perform acetal deprotection and cyclization with hydrazine hydrate in a one-pot procedure to give 3-substituted pyrazoles 141 (Scheme 48) [151]. Given that

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• ’-dimethoxybenzilhydrazone (X = H, Cl). In these cases, the diazo compounds directly underwent both Wolff rearrangement and overoxidations to yield a mixture of the corresponding diphenyl acetal and benzil dimethyl acetal (akin to the conversion of 132 into 133 in Scheme 27), respectively (Scheme 29) [78]. Using a similar

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

• excellent yields (71–89%). Dömling et al. have used glyoxal dimethyl acetal as orthogonal bifunctional monoprotected aldehyde to synthetize GBB dimers as potential fluorophores. More details are given in chapter 5 [43]. The GBB reaction can be exploited also in the late-stage functionalization of natural

• Ganesher [57] reported the one-pot cascade synthesis of indole-imidazo[1,2,a]pyridine hybrids 61 (Scheme 23). In this study, the convertible isocyanide 1-isocyano-2-(2,2-dimethoxyethyl)benzene (59, Kobayashi–Wessjohann isocyanide) was utilized as one of the precursors in the GBB reaction. The acetal

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• trap the phenoxonium cation formed in the oxidation as an acetal, that later were hydrolysed to the quinone. Formation of hydrogen gas as the cathode reaction caused challenges in the flow cell and were overcome by recycling the reaction mixture through the cell at increased flow rate several times

• estitmation of the HOMO/LUMO energies to shed more light on this transformation. The easy separation of the supporting electrolyte from the product will allow recycling and makes this a green transformation. Keywords: acetal formation; cyclic voltammetry; flow electrochemistry; green oxidation; polycyclic

• , formed o-dimethoxylated products (Table 3). The oxidation of 2-naphthol (1a) to quinone acetal 2 by PhI(OAc)2 (PIDA) has been reported to provide yields ranging from 63% [48] to 76% [49], compared to 84% in our electrochemical oxidation that afforded 30 mg of 2 after 4 h (Table 3, entry 1). The

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• -hydrazino form [17][24][25], we conceived the idea of reversing the reactivity of 4a–r in the six-membered cyclization process (N- vs O-annulation) through the generation of an electrophilic oxocarbenium [26][27] cation intermediate from the acetal residue at N-3 of the (thio)hydantoin core. To pursue our

• , in this case, the formation of carbinolamine 6a becomes predominant (45%), despite a small quantity of N,O-aminal 5j (14%) is also produced, by virtue of the alcohol released from the starting acetal 4j. Probably, the higher water concentration in acetonitrile shifts the equilibrium in favour of 6a

• over the time (Scheme 4). Within our proposed catalytic cycle, when compound 4j is utilized, methanol is released, due to the presence of a dimethyl acetal residue. Therefore, using molecular sieves (MS 4 Å) little alcohol molecules, such as MeOH, can be potentially trapped, allowing the insertion of a

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

• tetracyclic cage compound 51. Acetal opening in 51 afforded the keto-aldehyde 52 which underwent an intramolecular Cannizzaro reaction to give the trihydroxy acid 53, finally cyclizing to the lactone diol 54, elaboration of which led to the desired target (Scheme 18). An interesting application of the

• , formed the product 93 in 36–59% yield along with the overoxidized compound 95, and the dimer 94 as byproducts. However, upon reaction with methanol under acidic conditions, the product 93 and the dimer 94 underwent a smooth transformation to the methyl acetal in high yields. Similar exposure of the

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

• breakdown of ethyl vinyl ether and trapping of ethanol, yielding radical 84. To regenerate the photocatalyst, PhSSPh functioned as an oxidant. After protonation upon the β-elimination step, PhS− contributed a hydrogen atom to both 83 and 84, alongside regeneration of the HAT catalyst. Lastly, the acetal

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• electrophilicity. The products are finally generated by intramolecular formation of a semi-acetal. The yields were generally good (56–78%). The yields for pentafluoroethyl- and heptafluoropropyl-substituted derivatives were slightly better than the yields of trifluoromethyl-substituted derivatives which might be

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• presence of a methoxy group after the Heck–Matsuda reaction indicates methanolysis after arylation. Given the importance of the lactam rings, we envisioned a sequential Jones oxidation protocol without isolation of the methyl N,O-acetal products to obtain the corresponding lactams 4. As observed in

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• the acetal in 3 and 6 to the neighbouring C4-position (Figure 1) [19][20]. A variety of products were reported resulting from fluorination as well as the skeletal rearrangement, with the reaction outcome highly substrate-dependent. A key finding in this work was that the configuration of the alcohol

• separated by 0.21 ppm. In the 13C NMR spectrum of 11a–f, a ≈10 ppm upfield shift for the chloroacetal was seen to δ ≈92 ppm from the C5 acetal present in the starting materials. Only a single diastereomer was formed for all 3,3-disubstituted rearrangement products due to the hindrance on the endo-face, with

• 18 containing an exocyclic alkene was subjected to the reaction conditions, a mixture of benzylic chlorides (20) was formed in low yields, and trace amounts of the allylic chloride 19 was also isolated, the materials differentiated on the basis of the coupling of the acetal H5 with the respective

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• type (Scheme 1a, path a). However, attempts to form the desired imidazolium ring from 3 using triethyl orthoformate and different additives were unsuccessful. Similarly, an imine precursor 6, prepared in high yields by synthesising the known acetal-bearing oxazole 5 [21] and reacting it with 2,6

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• acetaldehyde dimethyl acetal as a masked form of acetaldehyde, which is hydrolyzed in situ, allowing for a higher product yield and fewer byproducts [15]. The group of Müller describes an elegant consecutive four-component reaction involving an alkynylation–cyclization–iodination–alkylation sequence toward

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• -butylsilyl-4,6-acetal-protected donor, as developed by the Kiso group [13][14], was chosen. After some initial testing the known N-Troc-protected donor 3 [15][16] (Scheme 1) was selected [17]. Since donor 3 possessed a Troc group, which contains 3 chlorine atoms, nucleophilic introduction of an azido group

• 10 furnished target 1 in a 90% yield. Formation of a stannylidene acetal via tin-activation was employed to achieve selective 3’-O-sulfation of compound 1 [27], with a variety of conditions being attempted (Table 1). With a TEG-N3 lactose compound, tin-activation was performed with Bu2SnO in

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• of polarized ketene-N,O-acetal to the alkyne β-carbon and trapping of the sulfonium cation at the alkyne-α-carbon afforded 5-(arylthio)-3,6-dihydropyridin-2(1H)-one 148. The coordination of a sulfonium electrophile to the C–C triple bond of 1-I occurred through cyclopropyl intermediate 1-I. The

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• intermediate 6.3 (ᴅ- or ʟ-threitol) that was then alkylated with mesityl lipid alcohol to produce 6.4 [80][81]. The acetal protecting group was removed in acidic conditions and then the intermediate 6.5 was subjected to oxidative cleavage to yield an aldehyde that was reduced with NaBH4 to produce 6.6a,b

• deprotonation of solketal in DMF followed by the addition of oleyl alcohol tosylate. 9.3 was isolated after the hydrolysis in acidic conditions of the acetal protecting group. The protection of the primary alcohol required a protecting group that can be deprotected without affecting the C=C double bond of the

• cesium cation with the halogen atom and the activation of the Sn–O bond of the stannylene acetal via a pentacoordinated intermediate with the fluoride anion [110]. The acetylation of the secondary alcohol and the deprotection of the primary alcohol with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• because of its high reactivity. Herein, we report the Enders-type cascade reaction using acetaldehyde dimethyl acetal, as a masked form of acetaldehyde. This strategy directly converts acetaldehyde, nitroalkenes and enals into stereochemically dense cyclohexenals in good yield and excellent

• enantioselectivity. Keywords: acetaldehyde; acetaldehyde dimethyl acetal; cascade reaction; multicomponent reaction; organocatalysis; Introduction Multicomponent reactions (MCRs) are chemical processes that involve three or more compounds, in which the product contains all the atoms of the reagents, except for

• , (E)-3-chloroacrylic acid, 2,4,6-trimethyl-1,3,5-trioxane (paraldehyde) [24][27], and acetaldehyde dimethyl acetal (6) [17][18][19]. On the basis of a long-term project based on masked reagents, our group has previously demonstrated the feasibility of the addition of a masked acetaldehyde 6 to

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• the ability of MgI2 etherate to act as a Lewis acid activator. The iodine counterion is coordinated to the Lewis basic oxygen atom of the acetal group to give the more Lewis acidic cataonic Mg-coordinated intermediate A. Intermediate A upon nucleophilic reaction with amines 20 yields B, which upon

• effect on product yield and no loss of catalytic activity. Moreover, a plausible mechanism for the constructions of N-arylpyrroles is shown in Scheme 17b. In the first step, the acetal group of 2,5-DMTHF (2) is protonated by β-CD-SO3H to produce intermediate A. Intermediate A is nucleophilically attacked

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• those with hydrocarbon, ether, acetal, and ester functionalities; although, aniline nucleophiles only resulted in the one step asymmetric ring-opening (ARO) product under the standard reaction conditions. Fortunately, the authors noted the addition of triethylamine allowed for aniline nucleophiles to

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• PMB group, in presence of DDQ under anhydrous conditions [18], gratifyingly afforded acetal 25 in 74% yield, whose stereochemical assignment by NOESY NMR experiment showed the syn stereochemistry of the acetal. By deduction, it was confirmed that the asymmetric boron aldol reaction between 8 and 15

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• hydroxybenzaldehyde 80 into the corresponding acetal followed by Ullmann-type coupling with 52, led to the formation of diaryl ether 83. Subsequent Corey–Fuchs reaction [49] and in situ alkylation led to formation of the propargylic alcohol 85. Deprotection of the aldehyde followed by chain elongation through the

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• aminals with allylic or allenylboronic esters (Scheme 25) [117]. The reaction was proposed to proceed by an activation of elemental gallium to a GaI species [(18-crown-6)-GaI·(dioxane)nOTf] 99, which abstracted methoxide from the acetal 100, to give an oxocarbenium 101 and GaIOMe 102. The gallium(I

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• acetal group could be used as substrates in an aza-Nazarov cyclization with the intermediacy of in situ-generated N-acyliminium ions (Scheme 1b) [21]. The first catalytic aza-Nazarov reaction was reported by Tius and co-workers in 2010, which involved the kinetic resolution of azirine derivatives via an

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• conditions of the Heck reaction to common scaffold 70 proved unsuccessful. Screening of several reaction conditions on different analogues led to the conclusion that reduction of the C8-carbonyl side and acetal deprotection to 71 are essential in order to create the 6/6/5/6-carbocycle in the presence of Pd2

• radical reaction [87]. Indeed, when ʟ-tyrosine methyl ester (154), 1,4-cyclohexanedione monoethylene acetal (155), and dehydroalanine derivative 156 were allowed to react in the presence of TFA, molecular sieves, 1 mol % of fac-Ir(ppy)3, and Hantzsch ester under blue LED irradiation at 40 W, this resulted