Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• rate of decomposition was reduced significantly (green line in Figure 3). The hydrolysis of the four hypervalent iodine(V) fluorides was also investigated in acetonitrile-d3 by adding 5 equivalents of water. All four compounds decomposed to their corresponding iodosyl compounds and the order of

• –22 gave insights into the geometries of the iodine(V) fluorides compared to the iodine(III) precursors. DFT results also suggested a possible reason for not being able to make iodine(V) amides 7a and 7b. An investigation into the hydrolysis of the four hypervalent iodine(V) fluorides revealed that

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• prepared and characterized. Surprisingly, a well-documented approach to obtain peptide-containing carboxylic acids through acid hydrolysis of the convertible isocyanide moiety in the Ugi bisamides proceeded in an unexpected manner in our case, leading to the formation of derivatives of amides of

• -called convertible isocyanides [27][28][29][30][31][32][33][34][35][36] in Ugi-4CR makes it possible to obtain carboxylic acids or esters after hydrolysis of the secondary amide group in the Ugi products (Scheme 2) [27][28][29][31][32][34][35][36]. Ugi bisamides modified in this way may be subsequently

• of Ugi bisamides based on pyrrole-containing β-chlorovinylaldehyde and convertible isocyanides. The subsequent post-transformation of the products by acidic hydrolysis conditions should then lead to an acidic component. However, due to the cascade nature of the multicomponent processes and the

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• acetylenedicarboxylate (DMAD). Although this [2 + 2 + 2] cycloaddition reactivity strategy has been reported under a variety of aryne generation conditions [17][18][19], in our hands we were only able to generate practical amounts of tetraesters 3 using the method reported by Peña et al. [18]. Hydrolysis of 3 with

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• phenanthren-4-ol (6b) provided the p-dimethoxylated product 8b in 66% yield (87 mg), consuming 8 F/mol over a duration of 12.7 h (Table 3, entry 5). Next, quinone acetal 8b was hydrolysed to phenanthrene-1,4-dione (9b) using aq acetic acid and HCl in 93% yield. The hydrolysis step went smoothly for all

• multiple products were formed. The lability of the acetals prompted us to submit the crude intermediate directly to hydrolysis without prior isolation (Table 4). As mentioned above, having an aqueous reaction mixture in the electrochemical oxidation will give reduced yields. The overall yield of 9b from 6b

• while isolating the acetal in between steps (Table 3, entry 5) was 57%, whereas the direct hydrolysis of the crude provided an increased yield of 74% (Table 4, entry 7). Further, chrysene-1,4-dione (4b) and chrysene-5,6-dione (4d) were obtainable this way (Table 4, entries 3 and 5), while 1b continued

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• -toluenesulfonic acid-mediated hydrolysis led to the cyclization reaction yielding the steroidal 17-spiro derivatives. The procedure was applied to synthesize drospirenone (Figure 1) and extended to build the spirolactone 23 from DHEA, a key intermediate toward the popular diuretic spironolactone (Scheme 7). 17

• obtained in a 43% overall yield after acid hydrolysis (Scheme 8). Unsaturated spiro-2H-furan-3-ones have been synthesized using various procedures. In 2000, Lee et al. employed an intramolecular condensation reaction involving an α-ketoester derived from prednisolone precursors to produce the target spiro

• conducted via catalytic hydrogenolysis, resulting in the formation of enaminoketones 32. Finally, enaminoketones were subjected to acid hydrolysis conditions facilitating ring closure and producing the spiro-2H-furan-3-ones 33 in moderate yield (Scheme 10). This procedure was also applied to norethisterone

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• achieve the total synthesis of 5 (Scheme 10A). Basic hydrolysis of the ester on the C1 side chain of 98 proceeded under mild conditions and furnished secondary alcohol 99. Subsequent oxidation of the two phenol rings of 99, catalyzed by the cobalt complex salcomine, afforded bisquinone 100. The subsequent

• hydrolysis of the ester and oxidation of the phenol rings allowed concise access to jorunnamycin A (103) in just 4 pots from 86 and 101 [102][106]. In subsequent work, Tanifuji and Oguri designed and applied eight variants of the peptidyl aldehyde (e.g., 104, 105) bearing various ʟ- and ᴅ-amino acids in

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• agarases to be encoded which belonged to the GH-50 agarase family. The enzymes were named AgaA50, AgaB50, and AgaC50. Biochemical characterization of these three enzymes revealed that AgaA50 and AgaC50 generated neoagarobiose products implying cleavage within the agarose polymer (endolytic hydrolysis). The

• macroalgae-derived Microbulbifer sp. YNDZ01 and expressed in E coli [88]. The recombinant enzyme Lip4346 showed high stability at high temperatures and in alkaline conditions, and tolerance to organic solvents. α-Amylases are glycoside hydrolases that catalyze the hydrolysis of internal α-1,4-O-glycosidic

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• fragility of secondary and tertiary benzyl fluorides, as they observe elimination and hydrolysis in many cases [20][100], thereby raising question marks over their suitability as synthetic targets. Monofluorinated methyl arenes, however, are much more stable to these decomposition pathways. The nucleophilic

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• assembly) activates the pyrazol-5-one 2a through hydrogen bonding and forms the corresponding enol. Simultaneously, the enol form of the pyrazol-5-one attacks the Re-face of the α,β-unsaturated ketone 1b to provide the intermediate 5 (Scheme 5), which after hydrolysis leads to product ent-3ba'. In situ

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• utilizing a hypervalent iodine-catalyzed oxidative hydrolysis reaction. This catalytic process provides both symmetrical and unsymmetrical dialkyl bromoketones with moderate yields across a broad range of bromoalkene substrates. Our studies also reveal the formation of Ritter-type side products by an

• alternative reaction pathway. Keywords: bromoalkenes; bromoketones; hypervalent iodine; oxidative hydrolysis; Ritter-type; Introduction Organic synthesis heavily relies on oxidative transformations to facilitate chemical reactions. One popular method for achieving these transformations is using redox-active

• catalytic amount of TsOH·H2O (0.2 equiv each), in the presence of m-CPBA (1.2 equiv) proved to be the most superior conditions (59% NMR yield, Table 2, entry 3). To rule out the possibility of direct involvement of m-CPBA in the oxidative hydrolysis reaction, 1a was reacted in the absence of any hypervalent

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• these products can be explained, similarly to the formation of 35a–f, by generation of intermediate Y which afforded iodonium salt Z upon addition of iodine. Cyclization by attack of the salicylate hydroxy group to carbon C5 gave intermediate AB. Hydrolysis of the iodide upon aqueous work-up to give an

• is, on the other hand, significantly more difficult and usually requires the use of the Schlenck technique to avoid hydrolysis of the moisture sensitive compounds. The handling of these reagents, which have to be stored at low temperature, requires some experience. In fact, the synthesis of the

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• radical resulting from reaction of o-anisidine with SeO2 is stabilized by resonance (Scheme 7). It combines with the hydroxyl radical and undergoes subsequent oxidation to give 2-methoxycyclohexa-2,5-diene-1,4-dione. This iminoquinone upon hydrolysis gives 2-methoxycyclohexa-2,5-diene-1,4-dione, and the

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• 2 via Baeyer–Villiger oxidation, followed by hydrolysis to yield another crucial aldehyde/acid intermediate 3 [11][15]. Commencing from 3, diverse ring rearrangement reactions can occur, leading to the formation of distinct products. In the AlpJ-catalyzed reaction, compound 3 undergoes ring

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• ) and FdZ (IId) form tetrahedral intermediates after hydrolysis of the N3–C4 double bond in the active sites of A3Gctd and A3A [59][60]. The intermediates formed had the same R-stereochemistry at the C4 atom of the nucleobase as previously observed for CDA, and thus confirming the general mechanism of

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• -cored halides can be broadened by converting C–Hal functions into different functional groups. For example, aldehyde and amine functionalities can be readily derived from C(sp3)–Hal functions through hydrolysis–oxidation [13] or substitution [14], respectively. This is of significant interest in the

• ) greater electrophilicity of the halo compound due to better leaving group ability of the halide ion, (iii) reduced toxicity, presumably due to faster hydrolysis [18], and (iv) easier oxidation of the halide to molecular halogen (E0 = 1.087 V (SHE) for Br2/Br−; E0 = 1.358 V (SHE) for Cl2/Cl−) [19

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• –elimination pathway will dominate over hydrolysis. This preference was crucial to prevent the formation of undesired carboxylic acid products [28][30][31]. These results also align with the observations previously reported by Takeda and co-workers [24]. The reaction was carried out using a large excess (10

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• . Conclusion In this study, novel analogues of the antiviral HeE1-2Tyr (1) were synthesized and evaluated with respect to the in vitro inhibitory activity towards SARS-CoV-2 RdRp. To obtain the benzoxazole analogue, a new synthetic strategy avoiding base-mediated hydrolysis was successfully applied. For the

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• carried out using 2 mol % of PdI2, 20 mol % of KI and 40 bar of a 4:1 mixture of CO–air, in methanol or ethanol in the presence of an ortho-ester (1:3 mixture) as solvent to prevent hydrolysis of the substrate. After 15 hours at 80 °C the indoles derivatives were isolated in good yields (Scheme 4). Two

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• temperature gave the NH-unprotected γ-lactam 5a and the drug (R)-rolipram 5b in 79% and 97% yields, respectively, with excellent enantioselectivity. Hydrolysis of γ-lactam 5a in 6 N HCl aqueous solution at 100 °C for 10 hours then led to the formation of (R)-baclofen hydrochloride (6) in 76% yield (Scheme 6

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

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• -workers also reported the modification of these 1,2-BCHs to increase the number of derivatives accessible using this approach (Scheme 3B) [38]. Transformation of the naphthyl ketone moiety of BCH (±)-25d by Baeyer–Villiger oxidation followed by hydrolysis gave carboxylic acid (±)-26. Through Curtius

• alkenes including acrylates, vinyl sulfones, and acrylamides could all be incorporated and the number of accessible bifunctional 1,2-BCHs was increased further by chemical transformation (Scheme 3D) [35]. Among the reported transformations were reduction of the ketone (to (±)-34), hydrolysis of the

• homologation and hydrolysis led to aldehyde (±)-46 which could then be oxidised to acid (±)-47 using a Pinnick oxidation. BCH 42b also led to ester (±)-48 via a Horner–Wadsworth–Emmons reaction followed by hydrogenation of the formed alkene. 1,2-BCH 44 could be turned into amine (±)-49 by oxime formation and

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• carcinogenicity [3][4][5][6][7][8]. Biotic and abiotic degradation of cyclic nitramines often produce linear nitramine byproducts. For example, degradation of RDX and HMX by microbes or alkaline hydrolysis forms the linear nitramine 4-nitro-2,4-diazabutanal (NDAB) [9][10][11][12]. Linear nitramines are also

• orthologous protein sequences and could facilitate NNG hydrolysis in the active site (Figure S4, Supporting Information File 1). The function of these residues are being investigated. There are also several nearby conserved basic residues. The significance of these residues will be further discussed below

• , Supporting Information File 1). Notably, the YjgF protein previously proposed to aid in deamination of imines – a proposed direct product of NNG degradation by NnlA – is absent [20]. This observation suggests this protein is not needed to aid in glyoxylate formation. Therefore, imine hydrolysis to glyoxylate

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• chiral auxiliary 10a, and following a survey of conditions and isolation protocols, a 90% yield was obtained when 10a was heated in the presence of 2 equivalents of SOCl2 and 5 equivalents of pyridine in DCE. Flash chromatography of the chloroalkyl ether 11a resulted in significant loss due to hydrolysis

• groups were small, and attempts to prevent the formation of 13d by slow addition of alcohol 10d to a solution of SOCl2/pyridine in DCE reduced the yield of 11d to 14%. Heating sulfite 13d with tetrabutylammonium chloride led only to hydrolysis back to 10d without rearrangement, indicating that these

• sulfites were not intermediates in the reaction manifold. Furthermore, the isolation of some starting alcohols in the reactions of 10b and 10d following chromatography was attributed to hydrolysis of the corresponding dialkyl sulfite 13b and 13d on silica, a process that can be acid or base-catalysed [26

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• polyketides or peptides, and form an ester bond. Then, they catalyze either intramolecular macrocyclization to give macrolactones or macrolactams with attacking of internal nucleophiles (alcohols or amine), or hydrolysis to release linear acids or peptides (Scheme 1b). Although TE domains may display

• TycC TE, the precursor was effectively converted into the macrocyclic tyrocidine A (1), exhibiting a low rate of substrate hydrolysis (Scheme 2a). In addition, TycC TE demonstrated a broad range of substrate tolerance, as it can cyclize a series of decapeptide-NACs that contain non-native residues in

• , resulting in daptomycin (12) formation with a ratio of cyclization to hydrolysis of 3:1 (Scheme 4a). The significance of single amino acids for daptomycin bioactivity was evaluated, for instance, the substitution of ʟ-3-MeGlu12 by ʟ-Glu12 in Dap yielded a 7-fold increase of the MIC against B. subtilis

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• GGPP, followed by hydrolysis by acid phosphatase. GC–MS analysis revealed that AsCPS synthesizes the same product to ObCPS_11g (see Supporting Information File 1, Figure S4A and B). It should be noted that the stereochemistry of CPP needs further verification due to the lack of chiral resolution of our