Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• , aldehyde, fluoro, chloro, and bromo were well-tolerated and compatible under the mild reaction conditions. Substrate 1p containing a methyl substituent on the phenyl ring could also participate in the reaction and furnish the desired product in moderate yield. However, attempts to prepare the substrates

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

• esterification reaction using methanol mediated by sulfuric acid under heating conditions to provide the compound in 81% yield. The methyl ester 5 was reduced to aldehyde 6 using DIBAL-H at −78 °C. While TLC analysis revealed complete conversion of the ester to aldehyde, the isolated yield was poor (20%). The

• 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

• acrylate aldehyde 9 in 61% yield. The next step involved the crucial reductive amination reaction between aldehyde 9 with indolamine 10, which had been obtained via Fischer indole synthesis – the reaction of phenylhydrazine with 5-chloro-2-pentanone [35]. Initial reduction attempts using sodium

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• ranging from 0 to 64% and the results were not reproducible. We could not identify the reason of these problems and could not overcome them. So, although compound 15 seemed an attractive starting material for introducing alkyl chains of pheromones 1–4, we decided to abandon this substrate and use aldehyde

• 19 instead. This compound was obtained from both aldehyde 15 and its precursor ethyl thioester methyl ester 14, respectively (Scheme 3). Both substrates 14 and 15 were reduced to the corresponding diol 17 with lithium aluminum hydride with 73% or 83% yield, respectively. Next, the selective

• protection of the axial hydroxymethyl group [32][38][39] was performed affording the product with a diastereomeric ratio of 6:1. Isomer 18 was isolated by column chromatography and subjected to a Swern oxidation to give the desired aldehyde 19 in nearly quantitative yield. This aldehyde derivative 19 was

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• products. An acetal-protected aldehyde could also be used providing enol phosphonate 3g in 52% yield. In this case, prolonged reaction times led to partial evolution of 3g into enol ether 4. This transformation may be explained by an acid-mediated elimination of ethanol likely caused by trace formation of

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• phenol 8 was generated by the reaction of 2-hydroxybenzaldehyde (5) and o‐phenylenediamine (7) at rt using a cobalt catalyst. In the next step, a benzimidazole-containing aldehyde 9 was obtained by the reaction of 6 with benzimidazole-substituted phenol 8. This ligand was immobilized on propylamine

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• present on the pypzs ligand, and activates the carbonyl group. The PCET occurs, furnishing a ketyl radical that can react with another molecule (ketone or aldehyde), delivering the pinacol product. A final HAT with another equivalent of HEH or HEH+ delivers the product, and the resulting radical cation of

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• signals, including one methyl, seven sp3 methylene, four sp2 methine (δC 143.1, 137.5, 129.1, and 126.8), one carboxy (δC 178.2), and one deshielded aldehyde or keto carbon signal (δC 199.8). Four degrees of unsaturation indicated by 13C signals were consistent with the number calculated from the

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

• accomplished in this stimulating field. Keywords: acylimidazole; N-acyloxazolidinone; N-acylpyrrole; N-acylpyrrolidinone; aldehyde; amide; copper catalysis; electron-deficient alkenes; enantioselective conjugate addition; Michael acceptor; thioester; Introduction Generating high molecular complexity and

• process allowing the selective introduction of a second methyl stereogenic center was then explored to develop a straightforward access to 1,3-deoxypropionate units, a scaffold ubiquitous in numerous natural products (Scheme 17) [40]. Starting from enantioenriched β-methylated aldehyde 37, the

• neglected to varying degrees, probably owing to their particular reactivity, which led to less impressive results. Nevertheless, these substrates present a high potential in total synthesis, since the chiral products can be easily transformed into various natural compounds. For example, the aldehyde

Allylic cross-coupling using aromatic aldehydes as α-alkoxyalkyl anions

• Akihiro Yuasa,
• Kazunori Nagao and
• Hirohisa Ohmiya

Beilstein J. Org. Chem. 2020, 16, 185–189, doi:10.3762/bjoc.16.21

• -catalyzed allylic substitution. Keywords: aldehyde; copper; copper catalysis; cross-coupling; palladium; synthetic method; Introduction α-Alkoxy-substituted carbanions (α-alkoxyalkyl anions) are useful C(sp3) nucleophiles for the construction of alcohol units found in a majority of pharmaceuticals

• and allylic carbonates 2. Methyl, tert-butyl and fluoro substituents were tolerated at the ortho- or para-positions of the aromatic aldehyde (3ba–da). 2,6-Dimethylphenyl- or 1-naphthyl moieties as the γ-substituent of the primary allylic carbonate were tolerated in the reaction (3ab and 3ac). Cinnamyl

• ) species B. The 1,2-addition of silylcopper(I) B to the aromatic aldehyde 1 [15][16][17][18][19] and the subsequent [1,2]-Brook rearrangement from the obtained α-silyl-substituted copper(I) alkoxide C forms the key intermediate, an α-silyloxybenzylcopper(I) species D. The transmetallation between D and an

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• organometallics in solution resulting in mixtures of the two reagents [15]. Thus, upon reaction with an aldehyde, mixtures of propargylic and allenic alcohols can be obtained through a chelate transition state (SE2'). Attempts to improve the regioselectivity of the propargylation reaction by using allenic

• results indicated that the substituent nature, whether electron-donating or electron-withdrawing, has no dramatic influence on the product yields. When the α,β-unsaturated aldehyde, cinnamaldehyde was used, the corresponding 1,2-addition product 2i was obtained exclusively. The chemoselectivity of the

• method was evaluated using aldehydes containing different functionalities. For example, the use of vanillin, an aldehyde containing the acidic phenol group as substituent, gave the corresponding product 2o in 93% yield in an 82:18 ratio of regioisomers. In the same way, when aldehydes containing an ester

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• following three categories: (i) by Wittig or Doebner reaction of indoles bearing a 3-aldehyde group; (ii) by 1,4- or 1,2-addition of α,β-enones or carbonyl compounds, followed by oxidation or elimination, respectively; (iii) by Pd-catalysed oxidative coupling of indoles with activated alkenes. Several

• different functional groups (Table 2). It was found that the reactions tolerated carboxylic acid, ketone, halogen (Cl, Br, I, and F), aldehyde, amide, primary amine, secondary amine, and phenolic functional groups to a reasonably acceptable extent. Recovery and recyclability of the Ru nanocatalyst The

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• )-(+)-goniothalamin 2 and acylated aza-goniothalamin analogue 3 [14][15][16][17][18]. Extension of the two-pot methodology to include a variety of different aldehyde starting materials. One pot synthesis of benzyl carbamate 4 reported by Veenstra and co-workers [19]. Formation of diene 5 in 66% through a one pot

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

•  1B). The two unidentified are putative sesquiterpenoids. Compound 3 is a putative hydrocarbon sesquiterpene with a molecular mass of 204 (Figure 1C). In contrast, compound 4 has a molecular formula of C15H22O and a molecular mass of 218 (Figure 1C). It was predicated to be a sesquiterpene aldehyde

• repeated three times with similar results. 1, linalool; 2, (E)-β-caryophyllene; 3, unidentified sesquiterpene hydrocarbon (compound 3); 4, unidentified putative sesquiterpene aldehyde (compound 4); 5, α-muurolene. B) Structures of known terpenoids. The structure of compound 2 shows the (−)-enantiomer of (E

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

• corresponding aldehyde in 1–2 mL MeOH (Ar degassed) was added upon vigorous stirring (for compound Z-1a: 4-(dimethylamino)benzaldehyde (170 mg, 1.14 mmol); for compound Z-1b: p-anisaldehyde (155 mg, 1.14 mmol); for compound Z-1c: veratraldehyde (189 mg, 1.14 mmol)). After the addition of the aldehyde, the

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• synthesis of thiazolidinedione derivatives is refluxing chloroacetic acid (2) with thiourea (1), followed by a Knoevenagel condensation with an aldehyde (Scheme 1) [25]. Results and Discussion Limited reports are available dealing with the synthesis of spiro derivatives of thiazolidine-2,4-diones [26][27

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• lactone carbonyl and oxymethylene group, and the presence of signals for putative aldehyde (δC 203.3; δH 9.49, s) and olefinic methyl (δC 19.5; δH 1.51, dd) groups. Key HMBC correlations (Table S10 in Supporting Information File 1) from 9-OH to C-11 and from H-11 to C-9 positioned the aldehyde on C-9

• point, the pathway branches out to the different (iso)nananagenines via combinations of hydroxylation at C-1 (or not) and one or multiple oxidations at C-11 and C-12. The oxidations of methyl to alcohol and alcohol to aldehyde could be catalysed by one of the two P450 oxygenases, or the short-chain

• dehydrogenase could oxidise the alcohol (at C-11 or C-12) to an aldehyde. Depending on whether C-11 or C-12 formed an aldehyde, further oxidation of the aldehyde to a carboxylic acid and condensation with the γ-OH group would afford the butyrolactone ring in nanagenines A–E and isonanagenines B/D, respectively

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 toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• . proceeding through a tert-butylimine intermediate (31) formed under Dean–Stark conditions [32]. This imine was reacted with NaOiPr to form the ether 32, which was subsequently hydrolyzed to obtain the desired aldehyde 28g in high yield. Reductive amination of the aldehydes 28f–h with 7 furnished amines 16f–h

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• with sodium methoxide in toluene and the resulting enolate was condensed with ethyl formate to give a keto-aldehyde, which tautomerized into the more stable β-hydroxyenone 4 [23]. The intermediate 4 was sufficiently pure for the subsequent transaldolization reaction with formaldehyde in the presence of

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• steps without purification of the intermediates. In this strategy, three different diversity sites could be generated, i.e., those derived from the isocyano and aldehyde components and a third one from the carboxylic acid used in the last acylation step. We sought to incorporate aryl or vinyl carboxylic

• , compounds 1a–o were reacted with diphenylacetylene under the optimized catalytic conditions to furnish – eventually – the corresponding tetrazole/isoquinolone hybrids 4a–o. We first fixed the R2 substituent as H (derived from paraformaldehyde as aldehyde component in the Ugi-azide-4CR, Scheme 1) to better

• peaks are reported. Melting points ranges were recorded on a Reichert Thermovar apparatus and are uncorrected. General procedure A for the synthesis of N-acylaminomethyltetrazoles First step: synthesis of N-tritylaminomethyltetrazoles [66]. Tritylamine (2.0 mmol, 1.0 equiv) and aldehyde (3.0 mmol, 1.5

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• 1,3-dicarbonyl compound was observed in the three-component reaction. Reacting it with amine 1 and aldehyde 7a under conditions similar to those for acetoacetic esters (8a–d) led to formation of a mixture of compounds 11 and 12 (Scheme 3). Heteroaromatic tetrazolopyrimidine 11 was obtained as a single

• product is the 5-hydroxy-containing tetrahydro derivative. In our experiments, the three-component reaction of amine 1 with aldehyde 7b and compound 13 in water under microwave irradiation afforded tetrahydro derivative 14 as a mixture of two stereoisomers. Inspection of the mixture by 1H NMR revealed

• the absorbance of the test solution. Ascorbic acid dissolved in DMSO served as the reference compound. General procedure for the synthesis of 9a–g. In a septum-sealed reaction vial, a solution of 5-aminotetrazole (1, 1.7 mmol), aldehyde 7 (paraformaldehyde 7a or acetaldehyde 7b, 0.15 g, ≈2 mmol) and

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• amphimedine (1) [11]. 4-Chloro-5-methylbenzo[c][2,7]naphthyridine (8) was oxidized at the methyl group to give an aldehyde. Subsequent modifications of the formyl group and Stille couplings at C-4 gave a number of 4,5-disubstituted benzo[c][2,7]naphthyridines (Figure 2A) [12]. Organolithium compounds were

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• N3P3Cl6 [33], the first step is the nucleophilic substitution with 4-hydroxybenzaldehyde in basic conditions. The second step comprises the condensation reaction of the aldehyde terminal functions with the phosphorhydrazide H2NNMeP(S)Cl2. This reaction affords the first generation (G1) dendrimer, having

• generation from the N3P3Cl6 core [34], and up to the twelfth generation from the (S)PCl3 core [35]. Thus, to incorporate the TPA fluorophores on the surface, it should have one function being able to react with P–Cl (or aldehyde) functions. For the incorporation of a TPA fluorophore at the core, it should

• synthesized. Synthesis of phosphorhydrazone dendrimers, from the core to generation 2. Generation 1 dendrimers with P(S)Cl2 or aldehyde terminal functions are represented both as the full structure and in the linear form with parentheses. Full structure of the generation 1 dendrimer bearing 12 blue-emitting

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• substrates was reported by Yu and co-workers (Scheme 13) [50]. Enantioenriched benzyl fluorides were obtained by aid of a chiral α-amino amide transient directing group (TDG). Notably, the condensation of this bulky amino amide with the aldehyde led to control of the stereochemistry of the C–H insertion step

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• nevertheless allows the conversion of 12-hydroxy-FDP (9) to dihydroartemisinic aldehyde (10), a biosynthetic intermediate and valuable precursor in the synthesis of artemisinin [29]. Results and Discussion Here we report that ADS accepts the bulkier FDP analogues 8-methoxy-FDP (11) and 12-methoxy FDP (12) as