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

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• -acetalation and decarboxylative [3 + 2] cycloaddition is shown in Scheme 4. With the promotion of the protonic solvent EtOH, compound 3 (N,S-acetal) from the condensation of cysteine and an aldehyde reacts with a second equivalent of aldehyde followed by cyclization to generate thiazolooxazol-1-one I

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• , the authors revealed the product 4a as E-isomer due to the strong intramolecular H-bonding. It was also observed that the labile acetal group in the product 4g remained unaffected during the reaction process under the standard conditions. Imidazole N-oxides reacted with ethyl cyanoacetate to produce

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• products existed as the pentacyclic hemiacetals 14. The 13C NMR spectrum for 14a had resonances at δ 144.5 and 104.4 ppm, consistent with an enol ether. In the 2D HMBC spectrum, crosspeaks between these double bond carbons were seen with the H2′-methylene and the H5′-acetal resonances. The characteristic

• ring-system resonances for the 6,8-dioxabicyclo[3.2.1]octane ring-systems were still present in the 1H NMR spectrum, with the H5 and H5′ acetal signals appearing as singlets at δ 5.39 and 5.30 ppm, and the H1/H1′ resonances each coupling to only one of the neighboring H7/H7′ methylene protons due to an

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• triple alkylation of ammonia with α-halohydrazones 9a–e following a protocol previously developed by us [35] (Scheme 2a). Halohydrazones 9a–e were prepared by condensation of readily available chloroacetone or bromoacetaldehyde (generated from the corresponding diethyl acetal) with hydrazides or

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• gave a reproducible 46% yield of 23. Optimal conditions were obtained using 1.8 equivalents of vinyl iodide and 1.7 equivalents of BuLi (Table 2, entry 6). It was difficult at this stage to determine the stereoselectivity of the coupling reaction since the starting acetal in 20 was a mixture of

• diastereomers. Therefore, we decided to oxidize the acetal in 23 to the corresponding lactone (Scheme 9). The acetal was first hydrolyzed to the hemiacetal 24 in quantitative yield. Oxidation of 24 proved delicate due to the lability of the tertiary allylic alcohol, and the presence of acid-sensitive protecting

• conditions. Cleavage of enol phosphate with Red-Al. Synthesis of the protected central fragment 11b. Synthesis and derivatization of the lactone fragment. Coupling reaction between alkyne 19 and ketone 11b. Coupling reaction between vinyl iodide 20 and ketone 11b. Oxidation of the acetal to the lactone

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• completed a selective anomeric deacetylation on a gram-scale using ammonium acetate in DMF, to afford hemi-acetal 15 in good yield (80%) [11]. This was followed by phosphorylation of the anomeric position using diphenylphosphoryl chloride as the phosphorous electrophile, following deprotonation of 15 using

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• oxidation at the methyl group C25 as well as C2, leading to the highly unusual acetal-epoxide proposed for ellarinacin (15). This work therefore not only represents an important example how a CYP51H evolved by gene duplication and neofunctionalisation from a sterol biosynthetic gene, but also demonstrates

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• cycloisomerization of the α-ketoester 22, which can be described as a Friedel–Crafts-type reaction or an aldol reaction of an S,O-ketene acetal (Scheme 4). The required ketoester 22 was synthesized from sulfonylchromenone 20, accessible from dihydroxyacetophenone 19 and thiol 18 derived from known alcohol 17 [11][12

• (−)-irofulven (87), Movassaghi et al. used a CuII-catalyzed asymmetric aldol reaction of O-silyl ketene S,O-acetal 84 with methyl pyruvate (85) to enantioselectively install the crucial tertiary TMS-protected alcohol in ester 86 (Scheme 14) [29]. Eleven further steps gave (−)-irofulven (87). 2. Mesoxalic

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• modified synthetic procedure [14]. Here, it was included the chromatographic purification of the final chloroformates, which led to removing of corresponding alkyl chlorides formed as byproducts. The aldehyde 17 was prepared by a different way, because the acid-catalyzed hydrolysis of its acetal

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• known as (±)-BCH-189 (1c). The key oxathiolane 4, a precursor of the corresponding nucleoside, was obtained as a 1:1 mixture of anomers (60%) from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na. The reaction was performed in toluene in the presence of p-toluenesulfonic acid

• recrystallized to obtain the enantiomerically pure ʟ-menthyl ester 35a (Scheme 8). Milton et al. [47] synthesized the key intermediate 38 by two synthetic routes. The first route involves a reaction of bromoacetaldehyde diethyl acetal (36) with a xanthate ester, followed by treatment of ethylenediamine, which

• condensation of the sodium salt of methyl 2-mercaptoacetate (3j) with bromoacetaldehyde diethyl acetal (36) in DMF solvent and further oxidation of the sulfide using m-CPBA, followed by Pummerer rearrangement using Ac2O and sodium acetate at 90 °C, which provides compound 37 (Scheme 9). α-Acetoxy sulfide

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• the mixture of 38 and 39 induced a second α-ketol rearrangement to 40 as a tautomeric mixture. The same research group later utilized the same [3 + 2] cycloaddition and α-ketol rearrangement approach to prepare the 2′′′-epimer of 35, which bears an inverted methyl acetal in the dioxane ring, but this