Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• complex heterocycle products of general structure 9 and 11. Interestingly, Wu et al. demonstrated that the reaction did not proceed when paraformaldehyde is used as the C1 synthon, indicating that formaldehyde is not involved in the reaction [43]. Furthermore, in isotope labelling studies using DMSO-d6

• using formaldehyde in only minor yields. This can be explained in terms of the regiospecificity of the reaction: when DMSO is used as the C1 synthon, two different ways of transferring the CH group at different positions in the pyrazole ring (12 and 12’) are allowed. However, this cannot be accomplished

• presence of an excellent leaving group (methyl sulfide) which permits further transformations during the domino sequences. This dual effect of MMS makes DMSO an interesting C1 synthon that works not only as a source of a methylene unit (-CH2-) in terms of formaldehyde surrogate, but also as a promotor of

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• -workers reported a dihydroquinine-derived squaramide-catalyzed (3 + 2) cycloaddition reaction of isocyanoacetates 26 and saccharin-derived 1-azadienes 14 [32]. In this work, the azadiene works as a C2 synthon, while the isocyanoacetate, bearing a protected carboxylic acid and a carbene-like divalent

• isocyanide carbon, behaves a C3 synthon affording benzo[d]isothiazole 1,1-dioxide-dihydropyrroles 27 bearing two adjacent stereocenters in high yields (27–98%) and with moderate to excellent stereoselectivities (54–97% ee) when using thiourea IX (Scheme 10). The cyclization was observed with all derivatives

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• fluoroalkyliodonium salts as sources of electrophilic trifluoroethyl synthon. Given the non-nucleophilic nature of the iodoarene byproduct, this protocol should not suffer from further reactivity that decomposes the ylide. We describe here the coupling of α-carbonyl sulfoxonium ylides with polyfluoroalkyl(aryl

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• synthon, which is used conveniently towards other applications, e.g., metal cluster synthesis, and halogen and hydrogen-bonded cavitands [77][78][79]. Our protocol works well with 2-methylresorcinol, as shown for products 1f and 1g, with significant yields around 80%. Electron-deficient and halogenated 2

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

• reactions in heterocycle synthesis [163][164] and certainly also for substituted pyrazoles. Four classes of 1,3-dipoles are considered as synthetic equivalents for the CN2 synthon: diazo compounds [165], nitrilimines [166], sydnones [167], and azomethinimines [168]. These intermediates undergo (3 + 2

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

• . Photochemical [2 + 2]-cycloaddition with fluorinated aldehydes and ketones gives access to a variety of fluorinated oxygen-containing heterocycles. We hope that this article will help chemists to utilize HFO-1132 and that this olefin will find applications as a useful synthon in organic chemistry. 1,2

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• complete conversion of the original olefins and the formation of allene 11. Thus, we have developed a method for the synthesis of the previously unknown allene 11. In addition, the possibility of using a mixture of olefins 3a,b made the allene 11 a more accessible synthon for studying its further

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• C6 synthon, by a Hunsdiecker–Borodin bromodecarboxylation, adapting the recent micellar conditions developed by Rajanna for the synthesis of alkenyl halides starting from α,β-unsaturated acids [34]. However, purification and concentration of 1-bromopenta-1,3-diene proved to only promote its

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• and carbohydrates to various carbocyclic scaffolds. This versatility arises from the possibility to chemoselectively cleave or reduce the sulfur-heterocycle to reveal a versatile C2-synthon. Keywords: 1,4-dithianes; 1,4-dithiins; 2,3-dihydro-1,4-dithiins; heterocycles; target synthesis; Introduction

• -fused dihydrodithiin ring is first hydrodesulfurized and then dehydroxylated in a stereospecific and stereoselective manner [62]. The dihydrodithiin building block 66 thus acts as a synthetic equivalent of an allyl alcohol anion and serves as a versatile synthon for de novo carbohydrate synthesis [63

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• to trisubstituted (E)-alkenylboronates 55, acting as a 1,5-synthon, similar to Gutierrez‘s vinylcyclopropanes (Scheme 4) [66]. Based on mechanistic investigations, Koh proposed the catalytically active iron-boryl species 57 is generated through the ligand exchange of 56 with B2pin2 which can undergo

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• . Therefore, there is great need to develop a more effective and rapid method for preparing diaryl methyl sulfones. p-Toluenesulfonylmethyl isocyanide (TosMIC), a versatile synthon in organic chemistry, has been widely used to synthesize a myriad of valuable chemicals due to its high reactivity shown by the

• important C1 synthon. Its special reactivity, such as the ability to react with electrophilic, nucleophilic, and radical reagents [25][26][27][28], determines that it can participate in many types of reactions such as multicomponent reactions [29][30][31][32], tandem reactions [33][34], and insertion

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• powerful nitrogen source for the synthesis of various N-heterocycles, such as isoquinolines, quinolines, pyridines, pyrroles, indoles, azoles, and azepines [40][41][42][43][44][45]. 1,3-Enyne, as a powerful Michael acceptor, is a wonderful synthon for the synthesis of N-heterocycles via tandem addition and

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• . Thus, further work is needed to develop a novel strategy for an efficient synthesis of such a versatile synthon. On the other hand, diethyl (2-oxoindolin-3-yl) phosphates 2 were easily prepared by the base-catalyzed phospha-Brook rearrangement of isatins 1 with diethyl phosphite [28][29]. This compound

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• retaining the stereogenic center. Divergence from the original route to pavettamine occurred after recovery of diol 5; and a different protecting group strategy was applied to arrive at synthon 4. The primary alcohol of the diol 5 was regioselectively protected using the trityl group under basic conditions

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• with a covalently attached fullerene molecule [86]. To this end, adduct 13 was obtained from 4-(tert-butoxycarbonyl)phenyldiazomethane and fullerene. Subsequent acid hydrolysis of the protective ester group quantitatively gave a derivative of carboxylic acid 14, a versatile synthon for the synthesis of

• methanofullerene-appended dicarboxylic acid 85 synthesized from 10 is a versatile synthon for conversion into numerous derivatives (Scheme 25). The reactivity of compound 85 was studied under DCC-promoted esterification conditions (see adducts 8 and 86) and amidation conditions (see adducts 21 and 22). Hummelen

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• , which proved to be a valuable synthon for the introduction of the CF3 group into molecules [125]. Thus, 199 exhibits a high reactivity towards many functionalities, as depicted below (Scheme 49). Interestingly, 200 and 201 are sufficiently stable to be synthesized, presumably due to electron

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding

• Subrata Nath,
• Alexander Kappelt,
• Matthias Spengler,
• Bibhisan Roy,
• Jens Voskuhl and
• Michael Giese

Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13

• behaviour of halogen-bonded liquid crystals has been reported. In 2014, Tothadi and Desiraju reported on a new supramolecular synthon based on the non-covalent interaction between 1,4-dinitrobenzene and iodobenzene [13]. Their structural analysis of a series of ternary cocrystals revealed that the nitro

• group is a suitable halogen bond acceptor, which interacts with polarised iodobenzene components in three different geometries – symmetrical, unsymmetrical or sidewise. Many other crystal structures support these findings and suggest the suitability of this synthon for the construction of supramolecular

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• obstacle was overcome by using a modified Fieser work-up procedure to yield the aldehyde 6 in high yield, 78%. Then, aldehyde 6 was converted to the α,β-unsaturated trans-ester 7 through a Wittig reaction with the phosphorane synthon 8, which was derived from ethyl bromoacetate at 60 °C for 8 h in THF in

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• BODIPY core has not yet been achieved. Inspired by the works of Waser and co-workers showing the gold(I)-catalyzed C–H electrophilic alkynylation of various heterocycles (e.g., pyrroles, indoles, etc.) with ethynylbenziodoxolone (EBX) as an activated ethynyl synthon [38][39][40][41][42], we investigated

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• product 59c, affording the key synthon 60 with a slight erosion of the optical purity (Scheme 22). α,β-Unsaturated N-acylpyrroles α,β-Unsaturated N-acylpyrroles were also investigated as Michael acceptors in enantioselective conjugate additions using organometallic reagents. In 2013, Endo and Shibata

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• cyclopentenone ring [37], as this heterocycle is a powerful synthon for the synthesis of a variety of bioactive target molecules, due to the broad diversity of chemical modifications available for the enone structural motif [38]. The most common approach to access such chemotype is the Pauson–Khand (PK) reaction

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• oxidation conditions. Based on this assumption, the corresponding silyl nitronate from 3-nitropropanal or its acetal were not tried for cycloaddition. We then set to liberate the β-hydroxy ketone synthon by ring opening of the isoxazoline 3 (Scheme 3). Raney-Ni-catalyzed hydrogenolysis in the presence of

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• /acceptor type C1 synthons [6][7][8][9][10][11][12][13][14][15]. In this context, sulfonyl oxime ethers are powerful acceptors of type C1 synthon [8][16][17], which terminates the multicomponent reaction by a β-scission of RSO2 radicals [18][19][20]. Recently, one of us reported on a three-component radical

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• which is finally easily removed [11]. Among three-carbon chirons related to Garner’s aldehyde derivatives of N-(1-phenylethyl)aziridine-2-carboxylic acid 5–8 (Figure 2) play an important role in asymmetric synthesis as they function as a chiral synthon combined with a chiral auxiliary [(R)- or (S)-1

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• performed a Cu(OAc)2-Et3N-mediated coupling reaction of α-azido ketones 115 with pyridinium ylides 114 using oxygen as a green oxidant (Scheme 40). The oxo-functionality present in α-azido ketones increased its acidity thus making it a good organic synthon. Optimization of the reaction conditions revealed