Synthesis of functionalized imidazo[4,5-e]thiazolo[3,2-b]triazines by condensation of imidazo[4,5-e]triazinethiones with DMAD or DEAD and rearrangement to imidazo[4,5-e]thiazolo[2,3-c]triazines

• Alexei N. Izmest’ev,
• Dmitry B. Vinogradov,
• Natalya G. Kolotyrkina,
• Angelina N. Kravchenko and
• Galina A. Gazieva

Beilstein J. Org. Chem. 2021, 17, 1141–1148, doi:10.3762/bjoc.17.87

• 4c–g,j–n bearing phenyl substituents contained no impurities of the corresponding isomers 5, while the structures 4a,b,h,i were isolated in individual form only during fractional crystallization from the reaction mixtures. It was previously shown [24][25][26] that the products of aldol condensation

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• aldol condensation [36]. The catalytic system for this transformation was adapted from earlier works [34][36] and included the addition of a 42% aqueous solution of HBF4 that facilitated consequent cyclization. A series of various β-(2-acylphenyl)enones and arylboronic acids was tested. Almost every

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• oxidation of (Z)-15a followed by immediate aldol condensation afforded racemic phenol ester (rac)-17 via aldehyde 16. However, several attempts to form enantioenriched aldol fragment 18 using both a chiral auxiliary [25][26][27][28] and catalytic asymmetric [29][30] procedures proceeded without success

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• later stage of the synthesis without the need of pre-installation of necessary functional groups as a reaction precursor, for instance, ring-closing metathesis, intramolecular aldol condensation, and others. One major issue that still needs to be addressed is the selectivity of the all carbon [3 + 2

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• double displacement with sodium sulfide to obtain thietane-3,3-diyldimethanol (13), which was further converted into two different thietanose nucleosides 2 and 14 [33] (Scheme 2). In the synthesis of sesquiterpene thioalkaloids, the method also was utilized. A double-aldol condensation of methyl

A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes

• Dragana Vuk,
• Irena Škorić,
• Valentina Milašinović,
• Krešimir Molčanov and
• Željko Marinić

Beilstein J. Org. Chem. 2020, 16, 1092–1099, doi:10.3762/bjoc.16.96

• 54, 10000 Zagreb, Croatia NMR Centre, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia 10.3762/bjoc.16.96 Abstract In order to prepare novel polycyclic derivatives of bicyclo[3.2.1]octadiene systems fused with a thiophene ring, photochemical cyclization and aldol condensation

• of the substituent could be seen through a shift of the aromatic singlet, which is, in the case of methoxy-substituted derivative 9, shifted downfield, due to the electronic and anisotropic effect of the methoxy group. In continuation of the study herein presented, the aldol condensation reaction of

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• can support removal of this substituent altogether, with only small potency loss (HITub-7) [20]. The progression and results of this SAR study are explained below in the section on bioactivity. General synthetic access Synthetic routes to HTIs are well established [26] and typically involve aldol

• condensation of benzaldehyde onto thioindoxyls. However, the key step is the formation (and where necessary, isolation) of the thioindoxyl species. In our studies, the electron-rich dimethoxy- and trimethoxy-substituted thioindoxyls were noted to be unstable to air, base, and silica gel during chromatography

Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• the phenyl ring was performed through the aldol condensation of indoxyl-3-acetate with the corresponding benzaldehydes under alkaline conditions (Scheme 1) [13]. All compounds 1a–c were obtained in good yields as pure Z-isomers as supported by the NMR data (Figures S5–S13 in Supporting Information

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• ]. Oxidation, iodocarboxylation and elimination yielded the lactone 43. A series of functional group manipulations provided enone 44, which underwent a cuprate-mediated Michael addition and liberation of the aldehyde 46 upon ozonolysis. After intramolecular aldol condensation the resulting enone 47 was

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• carried out in many research groups. The first racemic total synthesis of triptolide was reported 1980 by Berchtold and co-workers (Figure 2, route A, and Scheme 1) [66]. The key steps include: i) construction of the A-ring by aldol condensation, ii) construction of the butenolide (D-ring) by acid

• diastereomeric amides 39. Collins oxidation of 39 gave an aldehyde intermediate, which subsequently subjected to an aldol condensation using a ten-fold weight excess of neutral alumina quantitatively provided 40 and 41 in a small-scale reaction. The yield varied in large-scale reactions mainly due to the

• afforded triptolide (1, 21%) and 14-epitriptolide (48, 68%). Overall, the first total synthesis of racemic triptolide was finished from tetralone 22 in 16 steps. Although the intractable problems in some transformations, such as the neutral alumina-mediated aldol condensation to produce 40 and 41, the

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• tetraketide intermediate that can be cyclised by aldol condensation, followed by elimination of water to result in the aromatic ring system. Thioester hydrolysis and decarboxylation produce 29a that can be converted by SAM-dependent O-methylation into 24. In summary, this hypothetical biosynthetic mechanism

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• p-ethoxybenzaldehydes led selectively to aldol condensation products with (E)-configured double bonds in 30–40% yields. In preliminary experiments with an SF5-substituted acetic acid morpholide and p-nitrobenzaldehyde, a low amount of an aldol product was formed under similar conditions. Keywords

• (Table 2, entries 1–6). In contrast, from the reactions of 1 with benzaldehydes bearing electron-donating substituents (methyl-, methoxy-, ethoxy-) no aldol addition products could be isolated (Table 2, entries 7–9), but the aldol condensation products 4g–i were isolated in fair yields (see below). On

• state A are the major products of the aldol addition reactions. As mentioned above, aldol addition products were not isolated from the reaction of 1 with electron rich p-methyl-, p-methoxy-, and p-ethoxybenzaldehydes. Here, aldol condensation products 4g–i were obtained as single isomers after

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• ,S-acetals 9a–c since the X-ray crystal structure of Meldrum’s acid-based N,S-acetal was reported by Wentrup [84]. In addition, the intramolecular aldol condensation of Meldrum’s acids did not occur due to the ketone structures. Table 2 displays the 1H NMR result of the sulfur ylide-like intermediate

• methanimidothioate 7ao, and time dependent experiments of the intramolecular aldol condensation of N,S-acetal 7aa to 8aa in N,N-dimethylformamide-d7 at room temperature confirmed the formation of the stable sulfur ylide-like intermediates, thus indicating the successful transformation into thiophenes 8an, 8ao, and

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• aldol condensation of 2-methylpropanal with an aromatic aldehyde using a chiral amine as the catalyst. The attack of the hydroxy group of the resulting enantiomerically pure oxygen nucleophile 43 on vinyltriphenylphosphonium bromide (8) in the presence of a base, providing an ylide as an intermediate

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• (see Supporting Information File 1). This product presumably arose through aldol condensation of the readily enolisable ketone 22 with another molecule of 21. Overall then, it was concluded that approach #2 was not a viable strategy for synthesising target 6. Alternative substrates based on the

Curcuminoid–BF₂ complexes: Synthesis, fluorescence and optimization of BF₂ group cleavage

• Henning Weiss,
• Jeannine Reichel,
• Helmar Görls,
• Kilian Rolf Anton Schneider,
• Mathias Micheel,
• Michael Pröhl,
• Michael Gottschaldt,
• Benjamin Dietzek and
• Wolfgang Weigand

Beilstein J. Org. Chem. 2017, 13, 2264–2272, doi:10.3762/bjoc.13.223

• diseases and having only negligible side effects, low water solubility and fast degradation limit their potential medical application to this day [7]. The formation of the curcumin structure motif takes place by a base catalysed aldol condensation between the corresponding aldehyde and 2,4-pentanedione. To

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• hydrolysis of the oximino group gave target steroid 25 with the desired configuration of all stereogenic centers. In the attempted route to (+/−)-isocomene, Oppolzer and co-workers suggested pentalenone 29, accessible by an intramolecular aldol condensation/elimination of diketone 30, as a key precursor

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• ]. In this section some of the most important C–C bond forming reactions and their advantages are discussed. Aldol reaction In 2000, Raston and Scott first reported the aldol condensation reaction using veratraldehyde, 4-phenylcyclohexanone and 1-indanone in the presence of NaOH in a vibrating ball mill

• and the products were obtained in the yield up to 98% within 10 min (Scheme 1) [48]. However, the asymmetric version of a mechanochemical aldol condensation reaction was reported by Guillena and Nájera with co-workers (Scheme 2a) in 2008. Reactions between various ketones and aldehydes under solvent

• . Improvement in new synthetic methodologies under mechanomilling conditions with better results are always demanding, rather than “greening” the solution phase synthesis. Mechanochemical aldol condensation reactions [48]. Enantioselective organocatalyzed aldol reactions under mechanomilling. a) Based on binam

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• ’ during thiazole formation on large scale, requiring an oxidation–reduction sequence (90%) in this case. Completion of the total synthesis After evaluation of several strategies, the assembly of the two northern fragments 4 and 5 could be realized by an aldol condensation, involving a boron-mediated aldol

• reactions to set both the characteristic assemblies of neighbored methyl and hydroxy group bearing stereogenic centers. In addition, an aldol condensation was shown to enable an efficient route for construction of a delicate triene system. The final E-selective Heck coupling on a highly elaborate substrate

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• -1,3-indanodiones 77 (Scheme 26). It has been found that the intermediate 79 underwent the Stetter reaction to form the enolate intermediate 80, which next was transformed to the intermediate 81 via aldol condensation. The release of NHC gave the β-hydroxy ketone 82, which was deprotonated to enolate

• 276 [106]. The new catalytic reaction which replaced a previously described four-step synthesis [107], involved a tandem aldol condensation/dehydration and cyclization of the intermediate 275 to 276 (Scheme 77). In 1999, Ikeda and Mori have presented a cyclotrimerization of enones (e.g

The weight of flash chromatography: A tool to predict its mass intensity from thin-layer chromatography

• Freddy Pessel,
• Jacques Augé,
• Isabelle Billault and
• Marie-Christine Scherrmann

Beilstein J. Org. Chem. 2016, 12, 2351–2357, doi:10.3762/bjoc.12.228

• developed above (Scheme 1). In all cases, C was set at 0.64 and was calculated using Ncalc (Equation 16) or N = 35. The value of was determined according to the experimental data. Compound 1, obtained by aldol condensation (Scheme 1, reaction a) in 80% yield [8], was chromatographed on a manually packed

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• aldol condensation of aldohexos-5-ulose derivatives of the D-xylo and L-ribo stereoseries has been studied. Only one of the four possible inososes was isolated from both stereoseries in reasonable yields (30–38%). The results obtained, together with the previous findings for the L-arabino and L-lyxo

• ; intramolecular aldol condensation; stereoselective hydride reduction; Introduction Inositols are a family of biologically relevant compounds [1][2] constituted by nine stereoisomeric hexahydroxycyclohexanes (Figure 1): five have been found in nature (myo, scyllo, D-chiro, L-chiro, and neo), while the remaining

• -promoted [28][29][30] pinacol coupling of dialdehyde derivatives). A strategy related to the latter approach relies on a base-promoted aldol condensation of aldohexos-5-uloses followed by reduction of the carbonyl group, as reported in the retrosynthetic Scheme 1. This method again uses sugars as starting

Robust C–C bonded porous networks with chemically designed functionalities for improved CO₂ capture from flue gas

• Damien Thirion,
• Joo S. Lee,
• Ercan Özdemir and
• Cafer T. Yavuz

Beilstein J. Org. Chem. 2016, 12, 2274–2279, doi:10.3762/bjoc.12.220

• through metal-free Knoevenagel nitrile–aldol condensation, namely the covalent organic polymer, COP-156 and 157. COP-156, due to high specific surface area (650 m2/g) and easily interchangeable nitrile groups, was modified post-synthetically into free amine- or amidoxime-containing networks. The modified

• COP-156 and COP-157, through Knoevenagel nitrile–aldol condensation. COP-156 showed a high surface area (650 m2/g) with a hierarchical porosity, allowing synthetic post-modifications. The nitrile functional groups were first reduced to amine groups (COP-156-amine) and then through reaction with

Synthesis and properties of fluorescent 4′-azulenyl-functionalized 2,2′:6′,2″-terpyridines

• Adrian E. Ion,
• Liliana Cristian,
• Mariana Voicescu,
• Masroor Bangesh,
• Augustin M. Madalan,
• Daniela Bala,
• Constantin Mihailciuc and
• Simona Nica

Beilstein J. Org. Chem. 2016, 12, 1812–1825, doi:10.3762/bjoc.12.171

• the Kröhnke-type synthetic methodology [23][24] starting from azulene carbaldehydes (1) [25] and 2-acetylpyridine (Scheme 1). In the first step, the 1-azulenyl-2′-azachalcone precursor 2 is formed via a Claisen–Schmidt aldol condensation. This reaction was performed in an environmentally friendly

• ion. Conclusion Novel 4′-azulenyl-substituted terpyridines were efficiently synthesized following the Kröhnke methodology. The azulenylchalcone intermediates were conveniently synthesized using grind or microwave-assisted aldol condensation procedures. The target terpyridine compounds exhibit

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• scaffolds, we examined their one-pot transformation into α,β-diketoamides and the transformation of the latter compounds into nitrogen heterocycles bearing a peptide side chain (Scheme 1). Results and Discussion The starting 3-arylmethylene-2,5-piperazinediones 1 were readily available by aldol condensation