Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• -reductases. The reductant (usually NADH or NADPH) has to bind first to the enzyme, followed by the prochiral ketone in the second step. The chiral products are then released before the oxidised co-product. “Ping-pong, second”. Followed by most transaminases and lipase or esterase-catalysed acylation of

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• electrostatic interaction between carboxylate and iminium moieties undergoes a nucleophilic attack by isocyanide to generate nitrilium ion B. The intramolecular acylation of B forms C followed by Mumm rearrangement results in the formation of the desired products 22. The intermediate D may exist in equilibrium

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• -catalyzed acylation with isobutyric anhydride. This protocol allows for a reasonable synthetically useful s-factor of 20 and provides a novel entry to obtain this interesting planar chiral motive in an enantioenriched manner. Keywords: acylation; kinetic resolution; nucleophilic catalysis; paracyclophanes

• that allow for the kinetic resolution of racemic 4-hydroxy[2.2]paracyclophane (2) by means of an acylation with isobutyric anhydride (4a) in the presence of the chiral isothiourea catalyst HyperBTM (ITU 2). The reaction can be carried out with an s-factor around 20 and allows for the isolation of

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• , which can be considered an effective method for the generation of alkyl radicals without catalyst. In 2019, Yu and Zhang [15] reported a radical acylation reaction initiated by an EDA complex promoted by visible light. Imine 122 was employed as electron acceptor with α-keto acid 109 as electron donor to

• form the EDA complex, affording acylation product 123 under blue-light irradiation (Scheme 42). The quantum yield of the reaction was determined to be 0.08, suggesting that the reaction proceeded via radical coupling rather than a radical propagation. Moreover, the reaction was compatible with amides

• acylation product 123 initiated by an EDA complex. Mechanism of the synthesis of acylation product 123. Synthesis of trifluoromethylation product 126 initiated by an EDA complex. Synthesis of unnatural α-amino acid 129 initiated by an EDA complex. Synthesis of thioether derivative 132 initiated by an EDA

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• compounds 11 and 12, respectively, in two steps. In the first step, the ester derivatives were N-acylated by acetic anhydride in CH2Cl2 followed by hydrolysis using aqueous NaOH in THF to afford the required intermediates 3 and 4 in overall good yields. Compound 5 was obtained by direct acylation of the

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• amphiphilic C60 derivatives. Treatment of 14 with oxalyl chloride gives reactive acid chloride 15. Acylation of the presynthesized (ʟ-Ala-Aib)2-ʟ-Ala-OMe peptide with compound 15 gives the expected fullerene–peptide conjugate 16 (Scheme 8). A somewhat modified version for the synthesis of peptidofullerenes is

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• pyridine–P4S10 as sulfurization agent. The tertiary thiobenzamides 4a–c were synthetized by a one-pot acylation/thionation from the corresponding acid chlorides and dimethylamine [55]. Other chemicals and solvents were purchased from Acros Organics, Sigma-Aldrich, or Fluorochem and were used as received

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• and oxidation with sodium periodate, benzyl 2-azido-3-(((benzyloxy)(2-oxoethyl)phosphoryl)oxy)-2-methylpropanoate (69) was obtained. The latter was further transformed to the final phosphonodepsipeptide library 64 after the reductive amination with pyrrolidine derivatives 70 and acylation with a

• ester 87 was then coupled with dibenzyl (S)-2-hydroxypentanedioate (88) using BOP as the activating agent to generate the γ-phosphonodepsidipeptide 89. After hydrazinolysis, acylation with arenecarbonyl chlorides or arenecarboxylic acids, and further modification, the γ-phosphonodepsidipeptide

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• protecting group under acidic conditions was accompanied by cyclization in situ [14][15][34][35] and pyrrolizinone derivative 17 was obtained efficiently on a multigram scale over two steps. Originally, it was expected that adapting the conditions (NaH, RCOCl, THF) used for the acylation step in the

• spectrum) and a shift in the C(7a) resonance. The complication of solvent incorporation was avoided by running both the acylation and oxidative hydrolysis steps in acetonitrile, with water added in the second step. The oxidation step could be carried out either with a stoichiometric amount of I2, or just

• electrophilic activation and hydrolysis of the resulting electron-rich pyrroles in an overall N-acylation/C(7a) hydroxylation. This transformation is central to a synthesis of legonmycins A and B that requires just three laboratory operations from commercially available proline derivative 15. It is noteworthy

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• polyhydroxylated molecules of interest (e.g., antioxidants) [4][26] and of novel chromogenic feruloylated substrates with various physicochemical features for screening applications. Accordingly, we observed that transesterifications only occurred when using primary benzylic alcohols; no phenol acylation was

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Synthesis of 6,13-difluoropentacene

• Matthias W. Tripp and
• Ulrich Koert

Beilstein J. Org. Chem. 2020, 16, 2136–2140, doi:10.3762/bjoc.16.181

• subsequent reduction of the anthraquinone gave 1,4-difluoroanthracene. After ortho-lithiation and reaction with phthalic anhydride a carboxylic acid was obtained whose Friedel–Crafts acylation and subsequent reductive removal of the oxygen-functionalities resulted in the formation of the target compound. The

• two fluorine substituents was investigated. The retrosynthetic analysis for this strategy is shown in Scheme 1. The formation of the C5,5a-bond colored in red could be accomplished by an intramolecular Friedel–Crafts type acylation with the acylium-cation intermediate 6. The corresponding carboxylic

• acid precursor could be prepared by reaction of the anthracenyllithium 7 with phthalic anhydride (8). Intermediate 7 could be accessed by ortho-lithiation of anthracene 9. The synthesis of 9 by two consecutive Friedel–Crafts acylation reactions and reduction of the resulting anthraquinone could start

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