Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• employed as acylation reagents [1][2][3]. The strong C–F bond makes acyl fluorides relatively stable towards hydrolysis and easier to handle than other acyl halides [4][5][6][7][8]. Their reactions with nucleophiles are typically less violent than for the corresponding acyl chlorides with acyl fluorides

• of all these properties mean that acyl fluorides can provide significant advantages over acyl chlorides, especially for challenging acylation reactions [13][14]. Nevertheless, acyl chlorides still dominate in the literature; however, the recent development of safer and more practical synthetic routes

• -stoichiometric levels, further increasing the attractiveness of the method. Advantages of acyl fluorides compared to acyl chlorides, previous work on BT-SRF reagents [29][30][31][32][33] and a summary of this work on the BT-SCF3-mediated in situ formation of acyl fluorides and their use for the synthesis of

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• , 15a, and 15c, the desired 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines 7a–c were prepared in good yield (Table 1, entries 15–17, 59–66% isolated yield), enabling us to investigate the biological profiles as well as the reactions with acyl chlorides to form amides 16a–f (Scheme 2) [27]. These acylations

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• method to produce this versatile N-acyl carbazole motif involves combining 9H-carbazoles with acyl chlorides or similar activated acyl derivatives in the presence of a base (Scheme 1a) [13][14]. As an alternative, acyl carbazoles can be synthesized through step-wise metal-catalysed C–X-amidations

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

• analogues, whereas the variation of the acyl chlorides did not affect the reaction significantly. The synthetic application is demonstrated by formation of non-natural and natural dienone-containing terpenes such as β-ionone which was available in 4 steps and 6% overall yield. Keywords: cross coupling

• 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

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

• -unsaturated acyl chlorides to afford substituted α-methylene-γ-lactam heterocycles. The reactions proceed effectively in the presence of catalytic (20 mol %) amounts of AgOTf as an anion exchange agent or hydrogen-bond donors such as squaramides and thioureas as anion-binding organocatalysts. The aza-Nazarov

• cyclization of 3,4-dihydroisoquinolines with α,β-unsaturated acyl chlorides gives tricyclic lactam products 7 in up to 79% yield with full diastereocontrol (dr = >99:1). The use of acyclic imines in a similar catalytic aza-Nazarov reaction with 20 mol % of AgOTf results in the formation of α-methylene-γ

• catalytic aza-Nazarov reaction starting from cyclic and acyclic imines and TMS-substituted α,β-unsaturated acyl chlorides to yield α-methylene-γ-lactam heterocycles with high diastereoselectivities. We also report the results of our detailed mechanistic studies along with the necessary control experiments

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

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• radical source via a nickel/photoredox-catalyzed HAT processes (Scheme 28) [92]. The method was also compatible with other chlorine-containing electrophiles such as acyl chlorides 45 to afford methyl ketones 47 in moderate yields. Based on the detailed mechanistic studies, the authors proposed a catalytic

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• , carboxylic acids [16][17][18][19][20], acyl anhydrides [21][22][23], acyl chlorides [24][25][26][27], esters [28], thioamides [29][30][31], dithionates [32][33], or thiocarbamates [34] are employed as electrophilic components, but oxidative cyclocondensations with aldehydes have also been showcased [35][36

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• -designed complex [70]. In 2015, Grushin reported the generation of four well-defined CuC2F5 complexes, namely (Ph3P)2CuCF2CF3, (bpy)CuCF2CF3, (IPr*)CuCF2CF3 and (Ph3P)Cu(Phen)CF2CF3. The reactivity of the latter was studied for the synthesis of pentafluoroethyl ketones from acyl chlorides [71]. Indeed, the

• pentafluoroethylation of a large panel of acyl chlorides (23 examples) was achieved illustrating the synthetic utility and the efficiency of the newly designed (Ph3P)Cu(phen)CF2CF3 reagent (Scheme 16). Huang and Weng and co-workers reported the synthesis of air-stable perfluorocarboxylatocopper(I) complexes and their

Pd-catalyzed asymmetric Suzuki–Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position

• Yongsu Li,
• Bendu Pan,
• Xuefeng He,
• Wang Xia,
• Yaqi Zhang,
• Hao Liang,
• Chitreddy V. Subba Reddy,
• Rihui Cao and
• Liqin Qiu

Beilstein J. Org. Chem. 2020, 16, 966–973, doi:10.3762/bjoc.16.85

• rotary evaporator. Then, the corresponding arylamines (1.2 equiv) were added to the acyl chlorides, triethylamine (1.5 equiv) and DMAP (5 mol %) in DCM (20 mL). The resulting reaction mixture was stirred for 20 h at room temperature. The completion of the reaction was monitored by TLC. After completion

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• [118] coupled with aryl/heteroaryl halides using SIMesCuCl/Pd-RuPhos G3 to give the syn-isomers, while SIMesCuCl/Pd-P-iBu3 gave the anti-isomers. Styrenes could also be coupled with acyl chlorides [119] as electrophiles in the presence of B2(pin)2. Likewise, these same authors coupled 1,2-disubstituted

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

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

• acylation of the nitrogen atom with 13 selected acyl chlorides was synthesized starting from the aziridine ketone (2S,1'R)-97 (Scheme 25) [76]. To introduce the R absolute configuration at C3 (ceramide numbering) the aziridine alcohol (2S,1'R,1''R)-98 was stereoselectively obtained by reduction of the

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

• Ken Tamamoto,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 2375–2383, doi:10.3762/bjoc.14.213

• reagent could be easily transmetallated to copper species, which underwent cross-coupling reactions with various aromatic iodides or acyl chlorides to produce a broad range of CF2CF2-containing organic molecules in good-to-excellent yields. Therefore, the zinc reagent could become a new and practical

Functionalization of graphene: does the organic chemistry matter?

• Artur Kasprzak,
• Agnieszka Zuchowska and
• Magdalena Poplawska

Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177

• with improvements in the reactivity of carboxyl moieties. Carboxyl groups are not as reactive as the corresponding acyl chlorides or anhydrides. Activating a carboxylic group is therefore a crucial step in improving its reactivity toward nucleophilic reagents. A common approach is to employ

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• -dithioacetals [4] are of particular interest as attractive nucleophiles for the addition to halonium ions [5][6], acyl chlorides [7] and other electrophiles [8][9][10] and are broadly used as precursors for [2 + 2]-cycloaddition [11][12], (aza)-Diels–Alder reaction [13][14], and [3 + 2]-cycloaddition reactions

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• azirines and aldehydes also has been described by Lu and Xiao [27]. Hassner and Fowler described the reaction of azirines 2 with acyl chlorides with formation of intermediate adduct 3 to give oxazoles 4 in polar solvents (Scheme 1) [28][29]. In the latter reaction amide 5 was formed as a side-product and

• azides 1a–c. Yields refer to isolated yields. Synthesis of oxazoles 4 by addition of acyl chlorides to azirines 2, as described by Hassner et al. [28][29]. Preparation of 2-functionalized oxazoles 7 from 2-(chloromethyl)oxazoles 6 and their application to the synthesis of peptidomimetics 8. Integrated

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• POCl3 to afford the respective 1-arylpyrazolo[3,4-d]pyrimidin-4-ones 222 in a one pot single step procedure (Scheme 60). POCl3 acted as chlorinating agent as well as an oxidant in the reaction which in situ generated acyl chlorides from acids making the condensation and cyclization easier and faster

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• 4a–e were obtained in excellent yields when 2-ABA was treated with acid anhydrides as the acylating agents (Table 1, entries 1–5). Replacing anhydrides by acyl chlorides in the reaction the yields were slightly lower, and in some cases small amounts of the N,N’-diacylated products were also obtained

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• with acyl chlorides or chlorophosphates [11][12][13]. On applying the phosphoramidite chemistry, the phosphite triesters obtained are oxidized to phosphate triesters in each coupling cycle, whereas the H-phosphonate diesters may be stable enough to become oxidized only at the end of chain assembly

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• -tris(benzylamino)guanidinium chloride with acyl chlorides As an example of N,N’,N’’-tris(alkylamino)guanidines, we have recently described the synthesis of N,N’,N’’-tris(benzylamino)guanidinium chloride (4) [3]. Since the direct alkylation of TAG-Cl (1) was not possible due to the solubility problem

• hydrochloride (TAG-Cl) in aqueous alkaline solution, can be triply acylated to give 1,2,3-tris(acylamino)guanidinium salts only with acyl chlorides that are not easily hydrolyzed. On the other hand, 1,2,3-tris(benzylamino)guanidinium chloride underwent a threefold N-acylation under carefully controlled

• )guanidinium salts 4 and 5 with acyl chlorides to give 1,2,3-tris(acylamino)guanidines 6 and mesoionic 1,2,4-triazolium-3-aminides 7. See Table 1 for Ar, R and yields of 7. Protonation and methylation of 1,2,4-triazolium-3-aminides 7b,c. Catalytic hydrogenation/debenzylation of betaines 7. 1,2,4-Triazolium-3

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

• 11 (X = H/OH) and 2-(trifluoromethyl)acrylic acid (10) as a result of a Friedel–Crafts alkylation. An efficient and scalable one-pot process for the preparation of 1-indanones from benzoic acids has been described by Huang et al. [18]. In this synthesis, acyl chlorides formed in the reaction of

Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction

• Ananda Herath and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2017, 13, 239–246, doi:10.3762/bjoc.13.26

• are readily available (purchased or easily synthesized) than acyl chlorides allowing access to greater diversity. Finally, this method is easily adapatable to the synthesis of compounds with increasing complexity, as shown by our next set of experiments. To demonstrate the utility of the newly