Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• substituents at the C-2 position. As a way of expanding the scope of this methodology, we resorted to the α-C-acylation of β-enamino amides, a reliable reaction, the utility of which we have already demonstrated in other contexts [62][63]. Results and Discussion As the starting point of our synthetic

• key o-nitrobenzoyl intermediates 3 in a reaction with o-nitrobenzoyl chloride (Scheme 1, conditions ii). The acylation of 2 to 3 proceeded with variable yields, depending on the substituents R1 and R2. Derivatives 2 with a primary carboxamide group (R2 = H) gave generally lower and poorly reproducible

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• using acylation reactions (Scheme 7). After a suspension of 5 was refluxed in excess CH(OEt)3 for 28 h, a 58:42 mixture of the starting material and a new compound was isolated. This reaction completed in 8 h in the presence of HCOOH (2.5 equiv) and the new compound was isolated in 59% yield. According

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• developed a 2-azidobenzladehyde-based reaction sequence including a one-pot [3 + 2] cycloaddition, N-acylation and Staudinger/aza-Wittig reactions for the construction of pyrroloquinazolines and pyrrolobenzodiazepines [73]. The AcOH-catalyzed reaction of 2-azidobenzaldehydes, α-substituted amino acids and

• maleimides in MeCN at 110 °C for 6 h afforded the corresponding monocycloaddition compounds followed by acylation to yield intermediates 22. The subsequent sequential Staudinger/aza-Wittig reaction of intermediates 22 gave products 23a–g in 48–75% yields with 5:1 to 6:1 dr (Scheme 14). This one-pot reaction

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

• and S–S bonds. A plausible mechanism for the metal-catalyzed acylation and acylthiolation is illustrated in Scheme 33. Firstly, oxidative addition of palladium to the C–S bond of NTSE 1’’’ afforded intermediate I. The transmetalation from boron to palladium led to intermediate III, followed by

• acylation and acylthiolation. AlCl3-catalyzed synthesis of 3,4-bisthiolated pyrroles. α-Sulfenylation of aldehydes and ketones. Acid-catalyzed sulfetherification of unsaturated alcohols. Enantioselective sulfenylation of β-keto phosphonates. Organocatalyzed sulfenylation of 3‑substituted oxindoles

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• carried out by condensation of acetophenones with chloral under reflux in acetic acid using the known literature procedure [19] (Scheme 2). Based on another literature approach [20], compounds 1p–v were obtained by acylation of electron-donating arenes with Wynberg lactone [21] (Scheme 3). Additionally

• condensation of acetophenones with chloral in refluxing acetic acid. Synthesis of 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones 1p–v by acylation of electron-donating arenes with Wynberg lactone. Synthesis of 1-aryl-4,4,4-trichlorobut-2-en-1-ones 2 by dehydration of hydroxy ketones 1. Cyclization of 1-aryl

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

• benzylation produced 4.13. Then, the deprotection of the primary alcohol in acidic conditions allows introducing the phosphocholine polar head group by using POCl3 and the choline tosylate salt as reagents to yield 4.14. Finally, the debenzylation of the secondary alcohol and its acylation produce PAF 4.15. b

• ) The second scheme is shorter (Figure 4D) and starts with the acylation of 4.16 to produce 4.17. Then, the debenzylation of the primary alcohol produced 4.18. Interestingly, the migration of the acetyl group from sn-2 to sn-3 position was not observed. Finally, the installation of the phosphocholine

• group was introduced following the same method to produce PAF 4.15. By using the same methodology, the epimer of PAF 4.15 was synthesized. The group of Bittman reported in 1995 the synthesis of PAF with a four-step sequence starting from S-glycidol 5.1 in which the acylation of the sn-2 position was

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• esters and adopted the pre-acylation activation strategies [39][40][41]. Up to now, only one report employed an oxime for the generation of iminyl radicals to obtain the similar products, in which, substrates were limited to the electron-rich alkenes (Scheme 2b) [42]. On the other hand, sulfuryl fluoride

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• precursor 102 and the complementary aldehyde 103. 3.4 Catellani-type reaction The Catellani reaction involves palladium-norbornene cooperative catalysis to functionalise the ortho- and ipso-positions of aryl halides by alkylation, arylation, amination, acylation, thiolation, etc. [63]. Della Ca' et al. [64

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• isolated by a simple crystallization from the reaction mixture. Moreover, we observed the formation of compounds 17 during acylation of enamines 15 with oxalyl chloride to prepare the starting APBTTs 1 (Scheme 21). We noticed that in this case, compounds 17 were formed when HCl was not effectively removed

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• cyclization. The chiral starting material was prepared by an asymmetric Cu-catalyzed tandem conjugate addition/acylation sequence using ethyl cyanoacetate (Mander’s reagent) as a trapping agent (Scheme 56A). Activation of the zinc enolate by MeLi was necessary, but with optimum reaction conditions the authors

• -catalyzed conjugate addition and subsequent trapping of the zinc enolate by acylation or aldol reaction with an overall yield of 71–78% and good stereoselectivity (Scheme 57) [105][106][107]. Recently, Poock and Kalesse demonstrated the first total synthesis of halioxepine, a meridoterpene isolated from the

• Indonesian sponge Haliclona sp. [108]. Their synthesis takes advantage of the same tandem procedure that gives β-ketoester 219. The asymmetric conjugate 1,4-addition and subsequent acylation provided good stereocontrol and the authors could revise the thus far incorrectly assigned configuration of the target

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• changing the redox state of the aldehyde function, we have developed a number of directed Ru(0)-catalyzed C3-functionalizations of furfurylimines, such as alkylation [21], arylation [22], alkenylation [23] and acylation [24], as well as an Ir-catalyzed directed C3-silylation (Scheme 1a) [25]. These batch

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• -substituted o-aminobenzophenone, the synthetic procedure reported in [40] was applied. For acylation of the tert-butylacetanilide, PhCCl3 in the presence of AlCl3 was used. In the reported [40] reaction conditions, a complicated mixture of products was obtained. Lowering the temperature to −15 °C (in contrast

• to rt in [40]) allowed obtaining the targeted compound; however, acylation was accompanied with the migration of the t-Bu group yielding 2-benzoyl-4-tert-butylaniline and the corresponding 5-butylated isomer in a 10:1 ratio. Our attempts to separate the isomers were unsuccessful. However, as it will

Friedel–Crafts acylation of benzene derivatives in tunable aryl alkyl ionic liquids (TAAILs)

• Swantje Lerch,
• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2023, 19, 212–216, doi:10.3762/bjoc.19.20

• Swantje Lerch Stefan Fritsch Thomas Strassner Professur für Physikalische Organische Chemie, Technische Universität Dresden, 01062 Dresden, Germany 10.3762/bjoc.19.20 Abstract An iron(III) chloride hexahydrate-catalyzed Friedel–Crafts acylation of benzene derivatives in tunable aryl alkyl ionic

• acylation; homogeneous catalysis; ionic liquids; iron catalysis; TAAILs; Introduction The Friedel–Crafts acylation is one of the oldest metal-catalyzed reactions in organic chemistry [1] and allows for the synthesis of a broad range of diverse compounds [2][3][4][5]. Starting from electron-rich aromatic

• compounds, acylation is possible by an organic acid chloride/acid anhydride and a Lewis acid [6][7]. In the course of the development of ionic liquids (ILs) as a reaction medium for chemical reactions [8][9], the Friedel–Crafts reaction was also examined [10][11][12][13][14][15][16]. First protocols were

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• reactivity and complex synthesis. Based on previous work and own initial results, a new stereospecific sequential hydrozirconation/Pd-catalyzed acylation of enynes with acyl chlorides towards conjugated (2E,4E)-dienones is reported. We investigated a number of substrates with different alkyl and aryl

• example, the sequential hydrozirconation/carbonylation of propargylic ethers 18 reported by Donato [58] yielded α,β-unsaturated lactones 19. Beside the hydrozirconation/acylation sequence of nitriles utilizing acid chlorides published by Majoral/Floreancig [59][60], Cox revealed that terminal alkynes 16

• could be converted to enones 20 by hydrozirconation followed by Pd-catalyzed acylation with acyl chlorides 21 [61]. The substrate scope required aryl units at either alkyne or acid chloride unit. Recently, we could extend this method to alkyl-substituted alkynes 16 and acetyl chloride (22), providing

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

• leaving groups. The eliminating agent (AcCl) led to O-acylation of the intermediate 14 and resulted in deoxygenation through the release of AcOH giving 2H-imidazole derivatives. On the other hand, in case of “addition–oxidation” (SNH AO, path B), the oxidant DDQ picked up a proton from intermediate 14 to

• nucleophilic acylation catalyst in THF as solvent for 1 h. In this reaction, the yield for the transformation of 2-chloro-1-(4-methoxyphenyl)-4,5-dimethyl-1H-imidazole (19a) was 80% when 1.0 equiv TsCl was used. 2-Chloro-1H-imidazoles 20b,c and the corresponding brominated products 21a–c using TsBr were also

Ionic multiresonant thermally activated delayed fluorescence emitters for light emitting electrochemical cells

• Merve Karaman,
• Abhishek Kumar Gupta,
• Subeesh Madayanad Suresh,
• Tomas Matulaitis,
• Lorenzo Mardegan,
• Daniel Tordera,
• Henk J. Bolink,
• Sen Wu,
• Stuart Warriner,
• Ifor D. Samuel and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2022, 18, 1311–1321, doi:10.3762/bjoc.18.136

• 23% overall yield. First, hydrolysis of 1, in situ conversion to the acyl chloride and subsequent Lewis acid-promoted Friedel–Crafts acylation reaction produced compound 2 (Scheme 1), where the AlCl3 was also responsible for the demethylation. Compound 2 was then subjected to monoalkylation with 1,4

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• the acylation of purines from a regioselective to a regiospecific mode. Keywords: DFT; ferrocene; nucleophilicity; purine; steric effect; Introduction Nucleosides in which the sugar part is replaced with an organometallic moiety have attracted remarkable interest [1][2][3]. One important class are

• kinetic and thermodynamic control of the acylation reaction. Results and Discussion It was shown that the reaction between the pyrimidine anion (uracil, thymine, or 5-fluorouracil) and FcCOCl in N,N-dimethylformamide (DMF) proceeded in a full regiospecific mode [19]. In the purine series, however, the

• both isomers is, therefore, a competitive process. This confirms that the adenine anion behaves as an ambident nucleophile with two competing reaction centers at the N7- and N9-position [26]. It is known that acylation [25] or alkylation [27][28][29] of adenine is rarely regiospecific, and mixtures of

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• was successfully converted into the corresponding formamide 19 as was the poorly nucleophilic diphenylamine (Scheme 2, amide 20). Lastly, we aimed to apply the procedure to the acylation of a series of amines. To our delight, we successfully extended the methodology to the mechanosynthesis of amides

• -formylation reaction of several aromatic amines. On the other side, p-Ts-Im, activated by the acid reagent, proved an efficient activating agent under mild mechanochemical conditions for the formylation and acylation of those amines with less marked or limited (see protonated aliphatic amines) reactivity

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• as ligands in organometallic catalysts [9] and as versatile organocatalysts [10] in a very wide range of organic reactions such as classical benzoin condensation, transesterification, acylation, Knoevenagel reaction, Claisen condensation etc. The electrochemical generation of carbenes from ILs avoids

Introducing a new 7-ring fused diindenone-dithieno[3,2-b:2',3'-d]thiophene unit as a promising component for organic semiconductor materials

• Valentin H. K. Fell,
• Joseph Cameron,
• Alexander L. Kanibolotsky,
• Eman J. Hussien and
• Peter J. Skabara

Beilstein J. Org. Chem. 2022, 18, 944–955, doi:10.3762/bjoc.18.94

• using polyphosphoric acid [16] and sulfuric acid failed [42], therefore we tried Friedel–Crafts acylation. For that, 27 was hydrolysed to the corresponding diacid 28 with lithium hydroxide [15]. In a manner similar to [24], firstly, a ‘cold’ Friedel–Crafts acylation in dichloromethane was attempted, in

• the ring closure proceeded on one side of the molecule. It was assumed that this species precipitated, preventing further reaction. We thus turned to a ‘hot’ Friedel–Crafts acylation, in which the reaction mixture was refluxed after the addition of oxalyl chloride, followed by removal of the volatiles

• . Since the ring-closure with a ‘hot’ Friedel–Crafts acylation [43] led to an insoluble material, we wanted to synthesise a soluble derivative by attaching 4-(2-ethylhexyl)-2-methylthiophene groups. This was done by reacting intermediate 27 with compound 32, which was prepared as shown in Scheme 3. In a

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• acylation conditions in solution (Scheme 1) allowed us to reach the pentamer length with good yields for each substitution–acylation submonomer cycle (from 56 to 76% yield, Supporting Information File 1, Scheme S1). All compounds were acetylated at the N-terminus followed by removal of the Boc protecting

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• min. The authors propose that the reaction does not follow the mechanism of the Perkin process but proceeds via acylation of salicylaldehyde (44) to intermediate 45, which forms coumarin (46) in an intramolecular aldol cyclization. Therefore, O-acylation of salicylaldehyde (44) is completed at 150 °C

• 240 °C in one tube reactor, the reaction gives incomplete conversion and the yield of coumarin (46) drops to 21%. The authors proposed that under these conditions the reaction proceeds via the Perkin process, which is significantly slower than the O-acylation/aldol sequence [42]. An odorant that is

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• synthesized in 44–98% yield by acylation of isoxazoles 11, 12 and 13 with acyl chlorides in the presence of NaH (Scheme 4). For the preparation of isoxazole 1a propionic anhydride was used. Further, isoxazoles 1 were reacted with Mo(CO)6/H2O/MeCN under the optimal conditions to give pyridones 2 (Scheme 5

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• the axle, placing it away from the polymer backbone. By N-acylation of the ammonium group, a shuttling of the macrocycle towards the ester moiety is achieved, placing the chiral information of the macrocycle in closer proximity to the polymer backbone (polymers 33). The influence of the chiral BINOL