Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• removal of the silyl protecting group, followed by a carboxylation and acylation gave 13. Koide’s group [13] reported a second-generation route to 13, which utilized the Corey–Bakshi–Shibata chiral oxazaborolidine catalyst 21 [20] for the asymmetric reduction of the THP-protected 5-hydroxy-3-pentyn-2-one

• 22 to generate the secondary alcohol 23. The acylation of 23, followed by the treatment with Jones’ reagent effected the THP deprotection as well as an overoxidation to give 13. The syn-selective reduction of 13 was accomplished with a balloon worth of pressure of H2 in the presence of the Lindlar

• generate the mixed cyclic ketal 120. Finally, the removal of the C-4’ silyl protecting group, acylation of the resultant alcohol, removal of the C-4 silyl protecting group, and ketal hydrolysis generated FR901464 (1). Fragment coupling via olefin cross-metathesis Koide’s group was the first to demonstrate

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• - and 3,3′-O-acylation (Figure 1). The associated fatty acid acyl chains may be conserved within a species but can vary significantly in terms of the chain number and length for lipid A of different bacterial origins [3][4]. Lipid A represents a particularly important subject to research given the

• compound 13. Then, (2-naphthyl)methylene acetal [21] was used to protect the C-4,6-hydroxy groups using 2-naphthaldehyde dimethyl acetal and 0.2 equiv of camphorsulfonic acid (CSA). These protecting group manipulations resulted in the exposure of the C-3 hydroxy group in compound 14 for further acylation

• , followed by deprotection, acylation, and phosphorylation reactions (Scheme 4). The triflic acid (TfOH)-mediated glycosylation of donor 20 and acceptor 18 in the presence of molecular sieves in CH2Cl2 at −20 °C gave disaccharide 24 [14] in excellent yield (β-anomer only). The N’-Troc protecting group (non

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• -aminoquinoline delivered the arylated products in increased yields. Carbocyclic rings, long alkyl chains, methoxy, chloride, and phenyl groups were tolerated on the C–H substrates and electron-poor as well as electron-rich diazonium salts could be coupled smoothly. Pd-catalyzed acylation The dual catalytic

• system merging C–H activation and photoredox catalysis was also applied to C(sp2)–H acylation reactions via the generation of acyl radicals. In 2015, Li, Wang and co-workers reported the ortho-acylation of acetanilide derivatives using α-ketoacids as coupling partners and employing synergistic catalysis

• , liberating the expected product (Figure 28). In 2016, Wang et al. further demonstrated the possibility of extending this approach to the C(sp2)–H acylation of azo- and azoxybenzene derivatives (Figure 29) [90]. Similarly, acyl radicals generated by photodecarboxylation of α-ketoacids were engaged in a dual

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• proposal features a stepwise Mannich-type reaction of the enolized anhydride 17 to the imine component and a subsequent N-acylation reaction to form the lactam target product [24]. A respective Mannich-type intermediate has been recently isolated and subsequently converted into the target lactam product

One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions

• Gui-Feng Kang and
• Gang Zhang

Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120

• are versatile building blocks in organic synthesis, capable of constructing acyl derivatives [29][30][31][32][33] and ether derivatives [34][35][36] through acylation and alkylation under the appropriate conditions. In view of what was explained above, and as a result of our interest in developing

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• fragmentation, or H-abstraction (Scheme 16). A common way to access such radicals is through the decarboxylation of α-keto acids. Both reductive and oxidative strategies were implemented. In 2016, Wang and co-workers developed an organophotocatalyzed acylation of indoles (Scheme 17) [89]. They successfully

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• compound 8. Finally, the piperazinyl amide 4 was synthesized by of N-Boc deprotection. Another procedure for the synthesis of compound 8 involves acylation of compound 9, which was prepared by the reactions of 18β-glycyrrhetinic acid with 1-Boc-piperazine under similar reaction conditions. Compound 8 was

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• Figure 3, E0,0 is the energy gap between the ground state and the lowest triplet state, corresponding to the band gap in semiconductors. C–H acylation Decarboxylative acylation of acetanilides: In 2015, Wang and co-workers first reported the acylation of acetanilides via C–H functionalization using

• through this methodology is shown in Scheme 3, and the mechanistic pathway that is involved is displayed in Figure 7. Synthesis of fluorenones: Very recently, Ruzi et al. generated several fluorenone derivatives via dual photoredox-catalyzed deoxygenative intramolecular acylation reactions at room

• olefination. C–H olefination of phenolic ethers. Decarboxylative acylation of acetanilides. Synthesis of fluorenone derivatives by intramolecular deoxygenative acylation of biaryl carboxylic acids. Synthesis of benzothiazoles via aerobic C–H thiolation. Synthesis of benzothiazoles via oxidant-free C–H

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

• ). The acylation of the amino group was found necessary to allow for the cobalt-catalyzed reaction to proceed under a CO atmosphere. This step was also carried out in one pot after the KA2 reaction by diluting with pyridine and adding the acylating reagent, to achieve the corresponding product in

• slightly lower yield. Attempts to carry out the Pauson–Khand reaction directly on the amino group before the acylation step did not work, nor using a modified approach using ammonium chloride and 1.5 equivalents of Co2(CO)8 under an inert atmosphere, as reported for similar reactions in the presence of

• basic nitrogen atoms [28]. The variation of the alkyne component proved to give the KA2 coupling adduct when aromatic terminal alkynes were used, as shown in Table 1, entries 1 and 2 for those containing phenyl and thienyl moieties, resulting in 82% and 74% yield for the KA2 step. Subsequent acylation

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

• significantly lower biological activity compared to the parent compound (IC50 = 942 µM, U251 cell line) [15][16]. However, Pilli and co-workers were able to demonstrate that acylation of aza-goniothalamin 1 yielded analogues such as compound 3 with significantly improved biological profiles (IC50 = 11 µM, U251

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

• , so it was sought to minimise their exposure to these conditions during synthesis. In the end, we used two routes to the thioindoxyls: either Friedel–Crafts acylation of α-phenylthioacetic acids (which are easily accessible from thiophenols by alkylation using 2-chloroacetic acid, Figure 1b) or else

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• ]-rearrangement proceeded with additional partial enrichment of one enantiomer. The latter may have occurred through the preferential acylation of one of two diastereoisomers under the reaction conditions where the second chirality center at the phosphorus atom influenced the ratio of the acylation reaction. With

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• by BF3·OEt2-promoted glycosylation [18] with a short reaction time, exploiting anchimeric assistance, followed by Zemplén de-O-acylation. On the other hand, for the synthesis of the α-anomer 8, a SnCl4-promoted glycosylation was found to be very effective [19], but with a longer reaction time in

A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones

• Daniel P. Pienaar,
• Kamogelo R. Butsi,
• Amanda L. Rousseau and
• Dean Brady

Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287

• Daniel P. Pienaar Kamogelo R. Butsi Amanda L. Rousseau Dean Brady Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits 2050, Johannesburg, South Africa 10.3762/bjoc.15.287 Abstract The acylation of the acetonitrile anion with lactones and esters in ethereal

• catalytic amount of isopropanol, or 18-crown-6, was necessary to facilitate the reaction and to reduce side-product formation under ambient conditions. Keywords: acylation; β-ketonitrile; enolizable; trifunctionalized; sustainable; Introduction β-Ketonitriles represent highly versatile intermediates for

• , atom-economical ring opening of enolizable δ-valerolactone (3, Scheme 1). Although a two-step (or four-step, should hydroxy group O-protection prove to be necessary prior to acylation) protocol could, in theory, be envisaged to produce β-ketonitrile 2 from 3 by ring-opening esterification to afford

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

• cell lines, two bacteria, one fungus and one plant (Table 4). Compound 1 was inactive up to 100 μg mL−1 in all of the assays performed, suggesting acylation at 6-OH is important for biological activity. Compounds 4, 5 and 7 showed moderate antibacterial activity against B. subtilis, with weaker

• . The C-6 and C-8 lipid chain is likely produced by the HR-PKS encoded by gene FE257_006541, while the acylation could be attributed to the enzyme encoded by FE257_006545, which contains the conserved domain of the alpha/beta-hydrolase fold superfamily (which includes thioesterases and acyltransferases

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

• aldehydes were reacted in parallel with trimethylsilyl azide and tritylamine under microwave irradiation – followed by removal of the trityl group and acylation to afford the N-acylaminomethyltetrazoles 1a–s and 2a–l. The functionalized tetrazoles were obtained in moderate to excellent yields over three

• 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

• and the residue was used for the next step without any further purification. Third step: acylation of deprotected aminomethyltetrazoles. The N-deprotected aminomethyltetrazole obtained in the previous step was dissolved in dried DMF (4.0 mL, 0.5 M) in a flask provided with a magnetic stirring bar. The

Effect of ring size on photoisomerization properties of stiff stilbene macrocycles

• Sandra Olsson,
• Óscar Benito Pérez,
• Magnus Blom and
• Adolf Gogoll

Beilstein J. Org. Chem. 2019, 15, 2408–2418, doi:10.3762/bjoc.15.233

• well-established reactions (Scheme 2). The indanone is formed by intramolecular Friedel–Crafts acylation of 2 under microwave radiation as reported by Oliverio et al. [23]. The second step is the demethylation of indanone methyl ether 3 by aluminium trichloride in toluene at reflux [24]. Two indanone

1,2,3,4-Tetrahydro-1,4,5,8-tetraazaanthracene revisited: properties and structural evidence of aromaticity loss

• Arnault Heynderickx,
• Sébastien Nénon,
• Olivier Siri,
• Vladimir Lokshin and
• Vladimir Khodorkovsky

Beilstein J. Org. Chem. 2019, 15, 2059–2068, doi:10.3762/bjoc.15.203

• demonstrated the formation of 8 which shows 5 signals whereas the spectrum of 7a (or 7b) exhibits 12 resonances. Next, we found that acylation of 3 with a large excess of acetic anhydride or pivaloyl chloride in the presence of N,N-diisopropylethylamine afforded 1,4-diacyl derivatives 9 and 10a in high yields

• : nitrogen, blue; carbon, grey; iodine, violet. Synthesis of THTTA (3). Protonation, alkylation and acylation of 3. Charge transfer and delocalization within 3 and its diprotonated (6a) and monomethylated (7a) derivatives. Experimental and calculated selected bond lengths (Å). Supporting Information

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• in the side chain, the hydroxymethyl group in 9a–c was protected via acylation. Heating of 9a–c with an excess of acetic anhydride in chloroform quantitatively afforded the corresponding esters 10a–c. The products of acylation of the sterically hindered amino group were not detected in the reaction

• group of the cyclopentane ring (Scheme 7). The ester groups in 11a–c were easily cleaved in an aqueous–methanol solution of ammonia. Nitroxides 12a–c were isolated as orange compounds moderately soluble in water. Overall yields of these radicals via the acylation–oxidation–deprotection pathway were in

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

• , with the protecting groups removed except benzoyl. PTSA-catalyzed acetonization of 10 using 2.0 equiv DMP gave a mixture of two acetonides 19 and 13, which are separable by silica gel chromatography (Scheme 5a). In another trial (Scheme 5b), acylation of the two hydroxy groups in 9 yielded 20 in a

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

• protected diamine (R)-80a. Removal of the chiral auxiliary yielded the diamine (R)-80b which after acylation provided analogues (R)-76. Compound (R)-76 (R = C9H19) appeared inactive as inhibitor of human sphingosine kinases 1 and 2. 1,2-Diamino-3-hydroxy derivatives The interest in sphingoid analogues stems

• morpholine first required the reaction with iodotrimethylsilane and furnished diamino alcohol 82 which after N-debenzylation and acylation gave (1R,2R)-81. In a similar way other GCS inhibitors, e.g., ᴅ-threo-P4 (1R,2R)-83a and ᴅ-threo-4'-hydroxy-P4 (1R,2R)-83b (Scheme 20) were obtained and examined as

• 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

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

• ash-supported Sc(OTf)3 for Friedal–Crafts acylation reaction, also the group of Fukuzawa has exploited Sc(OTf)3 in the synthesis of N-substituted 1,4-DHPs [26][82]. Enhancement in reactivity and selectivity of many reactions, ability to polarize bonds upon coordination and thus altering their

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• reaction reported by Tan and co-workers using potassium tert-butylate in t-BuOH/dioxane at 55 °C for 6 h resulted in the desired isothiocyanate in only 34% yield [69]. In the next step, we investigated the acylation of the alcohol component by the isothiocyanate (Scheme 7, reaction 2). In the absence of a

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• bromide, see Supporting Information File 1) using 11 in the presence of trifluoroacetic acid afforded the corresponding homoallylic alcohol 14 and 15 in 84% and 92% yield, respectively. The next steps involved acylation of alcohol 14 and 15 using bromoacetyl bromide in refluxing toluene, which afforded

Mechanochemical Friedel–Crafts acylations

• Mateja Đud,
• Anamarija Briš,
• Iva Jušinski,
• Davor Gracin and
• Davor Margetić

Beilstein J. Org. Chem. 2019, 15, 1313–1320, doi:10.3762/bjoc.15.130

• Mateja Dud Anamarija Bris Iva Jusinski Davor Gracin Davor Margetic Ruđer Bošković Institute, Bijenička cesta 54, HR-10002 Zagreb, Croatia 10.3762/bjoc.15.130 Abstract Friedel–Crafts (FC) acylation reactions were exploited in the preparation of ketone-functionalized aromatics. Environmentally more

• employment of different aromatic hydrocarbons in conjunction with anhydrides and acylation reagents. It was shown that certain FC-reactive aromatics could be effectively functionalized by FC acylations carried out under ball-milling conditions without the presence of a solvent. The reaction mechanism was

• a few examples of FCRs employing manual grinding: reserpine acylation with AlCl3 [6] and acylation reaction of aromatics [7]. One of the reasons for this scarcity is the hygroscopic nature of the aluminum trichloride catalyst [8][9][10][11][12] when exposed to air humidity. This problem could be