Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• a smooth [1,3]-proton shift reaction with a high chirality transfer, affording the corresponding rearranged products in acceptable yields. Without purification, these products were subjected to acid hydrolysis and the subsequent N-Cbz protection, providing the optically active tetrafluoroethylenated

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• product 6 was not observed. Instead, among the several side-products formed, we were able to isolate α-aminoamidine 7, as the result of a 3C Ugi-type reaction between an aldehyde obtained from an oxidation–hydrolysis process of compound 5, tert-butyl isocyanide and 2 equivalents of aniline, and the

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• as 6-methyluracil (MU), 1,3,6-trimethyluracil (TMU), and pyridine (Py), and the results of the experiments are presented in this article. The hydroxy derivatives of MU and Py, obtained through oxidation followed by acid hydrolysis, possess compelling biological properties, rendering them practically

• 2 was no more than 15%. Subsequently, upon acid hydrolysis of compound 2, HMU (3) was produced. The addition of PcM to the reaction mixture resulted in a significant increase in the yield of compound 2 [13][22]. The catalysts were added in quantities ranging from 0.00001–0.1 wt %, with the amount of

• derivatives). Our study marks the first time pyridine has been involved in the peroxydisulfate oxidation reaction. The oxidation of pyridine (7) using APS resulted in a single product – pyridin-2-yl ammonium sulfate (8). Upon acid hydrolysis, this product yielded HPy (9, Scheme 2). The physicochemical and

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• . Mechanistically, this transformation can be understood as follows: first, a Br/Cl/CF3 radical is formed via anodic oxidation, which subsequently attacks the olefin. The newly formed benzyl radical is oxidized to a carbocation, which undergoes nucleophilic attack by DMF. Hydrolysis of the imine delivers the final

• method for the hydrolysis of hydrosilanes to silanols using N-hydroxyphthalimide (NHPI) as the hydrogen-atom-transfer (HAT) mediator [38]. To demonstrate the potential of their approach, they showcased the LSF of natural products such as (−)-borneol and (+)-fenchol, as well as pharmaceutical drugs

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• et al. [22] have demonstrated a combined use of flow and batch processes involving an electrochemical flow cell for the oxidation of furfuryl alcohols and subsequently utilizing the crude electrolysis mixture for hydrolysis in a traditional batch process to get the rearranged Achmatowicz product. As

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• detection of benzaldehyde which was considered to be formed by the NaClO-mediated oxidation of benzyl alcohol generated by hydrolysis. Changing the oxidizing reagent to crystalline NaClO·5H2O nicely solved the problem with the realization of 86% isolated yield of 2b by the utilization of this oxidant (2

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• -diaminonaphthalene derivatives 42, which after hydrolysis and extraction into toluene, were reacted with indole, 3-methylindole, 3,4-dihydroisoquinoline, and benzoyl hydrazone ethyl glyoxylate ester to afford terminal (E)-trifluoromethyl homoallylic amines 44 with up to 3 adjacent stereocentres with high to

• molecule. The BINOL catalyst 39 forming arylboronate species, enables the shift to occur asymmetrically. In the second step, the hydrolysis of unreactive diaminonaphthalene derivative 42 gives the poorly reactive and highly air-sensitive trifluoromethylallylboronic acid 43, but after the dehydration forms

• synthesis of homoallylic amines 117 and showed increased yields and enantioselectivities for aromatic aldehydes. In addition, a simple, ambient-temperature hydrolysis procedure was reported that yielded the unprotected analytically pure homoallylic amines in high yields without the need for chromatographic

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• and PIDA [30][33]. During this experiment, a small amount of hydrolysis product 4-(trifluoromethyl)benzenesulfonamide was also observed (1.2 mM, signals at 8.0, 7.9, and 5.86 ppm), but this compound did not greatly contribute to the broadening of O–H proton signal of HFIP as a separate 4.0 mM sample

• mixtures of aziridines are obtained from aziridination reactions of cis- or trans-β-methylstyrene, suggesting aziridine formation likely to operate via a step-wise pathway. d) Aziridination is not impacted by the presence of potential radical traps. e) PhIO, potentially generated by PhINTs hydrolysis, can

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• method to prepare [D1]-formamides (D–C=O) is through a Leuckart–Wallach reaction with an amine and [D1]-methyl/ethyl formate or [D1]-dimethylformamide [19][20]. Stockmann and co-workers produced [D2]-formamides (N–D, D–C=O) via acid-catalyzed nitrile hydrolysis with HCl and D2O [21]. Thus, using the

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• 5 was prepared from phthalimide (1, Scheme 1). Iodination followed by hydrolysis afforded 4,5-diiodophthalic acid (2) in 46.7% yield. Esterification with 1-hexanol yielded compound 3 in 56.8% yield and the subsequent Sonogashira coupling with trimethylsilylacetylene provided compound 4 in 80.0

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• Haifeng Yu Wanting Zhang Xuejing Cui Zida Liu Xifu Zhang Xiaobo Zhao College of Chemistry, Baicheng Normal University, Baicheng, Jilin 137000, China 10.3762/bjoc.20.190 Abstract An eco-friendly selective hydrolysis of chain α-oxo ketene N,S-acetals in water for the switchable synthesis of β-keto

• thioesters and β-keto amides is reported. In refluxing water, the hydrolysis reactions of α-oxo ketene N,S-acetals in the presence of 1.0 equiv of dodecylbenzenesulfonic acid effectively afforded β-keto thioesters in excellent yield, while β-keto amides were successfully obtained in excellent yield when the

• hydrolysis reactions were carried out in the presence of 3.0 equiv of NaOH. The green approach to β-keto thioesters and β-keto amides avoids the use of harmful organic solvents, thiols and thiolacetates as well as amines, which could result in serious environmental and safety issues. Keywords: α-oxo ketene

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• alternariol and 9-O-methylalternariol and the alternariol-9-O-sulfate (13–15) are conjugates repeatedly present in fungal sources [134][141][145] and the 3,9-O,O-disulfate of alternariol (16) has similarly been isolated [146]. Due to the instability of these sulfates towards hydrolysis they were typically not

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• showed that the activity of a difunctional organocatalyst in lactose hydrolysis was improved 5.2-fold by immobilisation on different solid supports that mimic the active site channels of enzymes [113]. In a solid-supported system, the solvent can exert a different influence on the catalytic activity

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• radical, which induces 5-exo cyclization. The following hydrogen abstraction, intramolecular ionic cyclization, and hydrolysis during chromatography on silica gel affords the cyclic amide in good yield. They further applied this radical cyclization reaction as a key step in the synthesis of (±)-α-kainic

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• -phenyl-2,4-hexanedione was generated in situ through acid hydrolysis of 1,1,1-trichloro-4-methoxy-6-phenyl-3-hexen-2-ones 71. Subsequent cyclization with hydrazine hydrochloride followed by hydrolysis of the trichloromethyl group led to 73. This intermediate was then reacted with 2,2,2-trifluoroethanol

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• electrolyte with potassium carbonate as a base and two platinum electrodes. Mechanistically, condensation of the two reactants formed isatin-derived acylhydrazone 37. Hydrolysis of the latter in the presence of the inorganic base gave rise to potassium carboxylate 39. Meanwhile, two consecutive SET oxidations

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• heteroaromatic halides. The reaction sequence utilizes a photochemically enhanced Negishi cross-coupling as a key step, followed by oximation and reduction. The prepared amino esters were validated for on-DNA reactivity via a reverse amidation–hydrolysis–reverse amidation protocol. Keywords: amino acids; DEL

• the most employed approach for producing this family of substrates [12]. Despite its effectiveness, this approach requires hazardous cyanides and harsh conditions for the subsequent hydrolysis of the nitrile or the hydantoin. Additionally, it carries significant limitations in its scope, reducing its

• proceeded smoothly yielding 4j in quantitative yield. However, obtaining compound 4r presented some challenges due to the resistance of ester 2r towards conventional oxidation methods (see Table S5 in Supporting Information File 1). Consequently, a multi-step process involving ester hydrolysis and

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• converted into the corresponding acids 4a,b by hydrogenolysis under mild conditions, which proceeded in quantitative yields (Scheme 4). It should be noted that this method of preparing β-lactam acids compares favorably with the alkaline hydrolysis of their methyl and ethyl esters, which does not always give

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