Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• a 4 mmol scale gave dimethyl ester 11a in 99% yield. Unexpectedly, the reaction of branched alcohols with diacyl chloride 2a failed. For example, the reaction with benzyl alcohol resulted in the formation of an overly complex mixture of products. Adding bases to trap HCl did not improve the

• reaction of more branched alcohols failed. Such esters could be prepared from the dicarboxylic acids using traditional activation or OH-insertion reaction of carbenes formed by irradiation of the appropriate diazo compound. Approaches to 2H-azirine-2,2-dicarboxylic acid derivatives. Synthesis of 2H-azirine

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• nucleophiles In 2000, Hara and co-workers reported the fluorocyclisation of unsaturated alcohols and carboxylic acids promoted by HVI reagents (Scheme 11) [36]. Using 4-tolyl difluoroiodane 10 as the reaction promoter, and pyridine·6HF as a source of fluoride, a range of unsaturated alcohols 23 to fluorinated

• tetrahydrofurans 25 and tetrahydropyrans 26. Unsaturated carboxylic acids 24 was also cyclised to form 5-membered fluorinated lactones 27. The mechanisms proposed for the cyclisation of unsaturated alcohols and carboxylic acids both proceed first through the activation of the alkene by the iodane (Scheme 11). The

• the oxyfluorination of alkenes in 2015 [31]. Under identical conditions to the aminofluorination using 1-fluoro-3,3-dimethylbenziodoxole (12) with Zn(BF4)2 catalyst, unsaturated alcohols were cyclised to fluorinated tetrahydropyrans 26 and oxepanes 28 (Scheme 12) in 1–2 hours in good yields. Gulder

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• systematic catalyst structure–reactivity and selectivity relationship study. The observed catalyst structure–enantioselectivity relationship of the present allenylation reaction was found exactly opposite to that of the analogous allylation reaction. The method provided eleven α-allenic alcohols in 22–99

• ; Introduction Enantioenriched α-allenic alcohols are an important class of chiral building blocks used for the chemical synthesis of biologically relevant molecules [1][2][3][4][5]. Their strength comes from the rich synthetic versatility [6][7][8][9] and biological relevance [10] of the allene functionality

• . Accordingly, the development of efficient access to optically active chiral α-allenic alcohols continues to be of significant interest in organic chemistry [11][12][13]. The asymmetric catalytic addition of allenylation reagents to aldehydes provides direct access to chiral α-allenic alcohols in an

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• further attacked by TBHP to give product 61. Benzyl alcohols 62 were also converted into tert-butyl perbenzoates 63 under the action of the TBAI/TBHP system (Scheme 22) [65][66]. During the process, TBHP oxidizes TBAI into iodine, which reacts with the second TBHP to generate tert-butylperoxy radical B

• , which is captured by TBHP. Pathway II: the recombination of the C-centered radical C and tert-butylperoxy radical B. The three-component approach to 4-(tert-butylperoxy)-5-phenyloxazol-2(3H)-ones 82 from benzyl alcohols 80 and isocyanates 81 using the Cu(II)/TBHP system was developed (Scheme 29) [76

• provides radical E. tert-Butylperoxy group transfer from Co(III)OO-t-Bu A to E gives the coupling product F, which gives the final three-component product 118 and releases the Co(II) catalyst. A copper(0)- and cobalt(II)-catalyzed difunctionalization of enynes 119 with the sp3 α-carbon of alcohols 120 and

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• converted into the methyl esters 10 (54%), 11 (52%), and 12 (46%). The benzyl-protecting group was removed hydrogenolytically to give products 13 (85%), 14 (65%), and 15 (99%). The alcohols were then converted to the triflates 16 (28%), 17 (41%), and 18 (63%). We have chosen 3,4,5-trimethoxybenzaldehyde (19

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• the gas phase than in solution [32][33], it has remained a challenge to control such reactions. Our group has recently reported a mechanochemical difluoromethylation of primary, secondary, and tertiary alcohols [34], yielding products with difluoromethoxy groups, which are promising organofluorine

• compounds [35][36][37][38]. Notably, also sterically hindered alcohols, which are typically less reactive in solution, could be applied under solvent-free conditions in a ball mill [39], which was attributed to a better accessibility of the difluorocarbene in the mechanochemical environment [40]. Motivated

• reaction conditions were chosen based on those reported by Ni, Hu and co-workers for the difluoromethylation of alcohols in solution [39]. The two activators KFHF and KOAc were investigated in a dichloromethane/water mixture at room temperature for 10 h. In both cases, the yield of 3a was negligible (with

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

• diastereomers 12 and 13 are often easily separable, and each diastereomer of optically active alcohols or amines can be obtained with an excellent optical purity (reactions 3 and 4 in Scheme 1). To the best of our knowledge, these are the only four works for the preparation of optically active substances having

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluorine-containing building blocks have been developed [21][22][23][24][25]. Jubault and Poisson et al. reported SN2’ reactions of hydride or alcohols to electrophilic fluorine-containing alkenes gave the corresponding fluoroalkenes (Scheme 1B) [21]. In recent years, many fluorine-containing coupling

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• synthetic route. Results and Discussion Initially, 3-arylbenzofuran-2(3H)-ones 3aa–ma were prepared following a SbCl3-catalyzed Friedel–Crafts alkylation of phenols 1a–m with benzylic alcohols 2a–d, earlier reported by us (Scheme 1) [21][22][23]. All the synthesized 3-arylbenzofuran-2(3H)-ones were

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• -hexadecylglycerol, as well as other common long-chain alcohols and amides. Although a general defensive function has been proposed for snake abdominal scent glands, the specific chemistry and moderate amounts of acids reported here may suggest a function in chemical signaling for the Mangshan pit viper. In addition

• (see, e.g., [1][2]). Comparative analysis of SGS through GC–MS has revealed an assortment of lipids (reviewed in [2]), such as cholesterol [3][4][5][6][7][8], carboxylic acids [4][5][7][8][9][10][11][12], alcohols [8], 1-O-monoalkylglycerols [6][8], and others [13]. Nitrogen-containing compounds

• components, carboxylic acids, alcohols, glycerol ethers, amides, and volatile compounds such as phenol, benzaldehyde, or indole were present (Figure 1 and Table 1). While some of these compounds were easily identified, a group of diketopiperazines (DKPs) and a series of unknown putative carboxylic acids (A–F

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

• activate alcohols presents a significant synthetic challenge. The carbazate substrates are easily prepared from ubiquitous alcohol precursors. The first stage of the transformation involves the sequential anodic oxidation of the carbazate and subsequent deprotonation to form a diazenecarboxylate. Further

• method for the formation of C–S bonds [25]. This method achieves the difunctionalization of a carbon atom by reacting isocyanide 2-isocyanoacetate with a thiophenol and an alcohol. The scope is very broad for thiophenols, alcohols, and isocyanides, and even alkyl thiols are compatible. In addition to

• aliphatic alcohols, benzyl alcohols are also suitable reagents. Numerous LSF examples and upscaling were demonstrated. The mechanism involves two anodic oxidations: first, the thiophenol is oxidized at the anode, forming a sulfur radical that attacks the isocyanide. The newly formed carbon radical is then

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

• and development of a visible light-assisted modular photo-flow reactor with a seamlessly integrated post-synthetic work-up procedure enabling the efficient synthesis of dihydropyranones from furfuryl alcohols. The reaction uses sun light as green energy source, and the novel photo-flow reactor

• platform developed with an integrated system enabling a downstream process in a time and labor-efficient manner which facilitates the Achmatowicz rearrangement, resulting in a fast (10 min) formation of the dihydropyranone products. Keywords: Achmatowicz reaction; flow chemistry; furfuryl alcohols

• ; photocatalyst; sunlight; Introduction The furan ring moiety is present in several natural products [1] and serves as a key precursor to 1,4-dicarbonyls [2], cyclopentanones [3], and carboxylic acids [4], in synthetic organic chemistry. Furfuryl alcohols, a family of 2-substituted furan molecules, are

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• containing an alkene group was readily synthesized starting from commercially available 4-acetoxy-2-azetidinone (6) by nucleophilic displacement of the 4-acetoxy group with allylic alcohols promoted by Zn(OAc)2 (see compounds 8a–h, Scheme 1) [45]. Similarly, enantiopure derivatives 10c–f were synthesized

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• ][9][10][11], yielding phenylacetic acids. For example, Troupel et al. successfully performed electrochemical reduction of benzyl ethers and several esters such as acetate, trifluoroacetate, benzoate, and dibenzyl carbonate derived from benzyl alcohols, including 1-phenylethanol compounds, in the

• contrast, little attention has been paid to electrochemical direct carboxylation of benzyl alcohols, although it is a more straightforward and simple protocol toward phenylacetic acids. In 2015, we reported an electrochemical direct carboxylation of benzyl alcohols having an electron-withdrawing group on

• the phenyl ring [17]. To the best of our knowledge, this is the first report on electrochemical carboxylation of benzyl alcohols. Only benzyl alcohols having an electron-withdrawing group, such as cyano or ester in the ortho- or para-position of the phenyl ring, were efficiently carboxylated by

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

• of racemic, configurationally stable sec-allylboronates (±)-35 (Scheme 8A). Using 2.5 equivalents of racemic boronate 35, the reaction with aldehydes produced enantioenriched Z-homoallylic alcohols 36. While this protocol was effective for aldehydes, it proved challenging to perform it with N

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

• product. Such a process would account for the simultaneous stereochemical scrambling observed and the lack of radical trapping noted. Conclusion In conclusion, we describe the activation of simple iminoiodinane reagents by fluorinated alcohols, such as HFIP. While most iminoiodinane reagents do not engage

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• enantioselectivities of a kinetic resolution of benzyl alcohols and an enantiodivergent fluorination of allylic alcohols, observing good correlations for both reactions. Since then, the proposed NCI descriptors have been successfully applied to multiple different reactions, such as an allenoate Claisen rearrangement

• mechanistic breaks in Hammett plots. However, deliberate data set design to systematically cover the relevant chemical space can aid in detecting outliers and aid in creating more relevant models, as demonstrated by Neel et al. for an enantiodivergent fluorination of allylic alcohols, catalysed by a CPA as

• additions to imines, comprising alcohols, thiols, phosphonates, diazoacetamides, peroxides, benzothiazolines and more as nucleophiles. Apart from reactant classes, the reactions also vary in additives, and solvent among others. Since these reactions all adhere to the same mechanism of enantioinduction, the

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• alcohols, polyols, polyions or polymers, has a positive effect on protein stability and the soluble fraction expressed with CFPS [17]. The variable composition of CFPS systems with a high number of ingredients and possible reaction conditions [13] thus opens a large parameter space. In addition, non

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

• ][62][63][64], we conducted research on their organic reactions in water and reported some good results, such as thioacetalization using ketene dithioacetals as odorless thiol equivalent [65], Friedel–Crafts alkylation of cyclic ketene dithioacetals with alcohols [66], the hydrolysis of chain α-oxo

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

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

• iodoalkanes 89. Subsequent reaction with acylsilanes 90 leads to alcohols, which react by Brook rearrangement to enoxysilanes and form the intermediate 92. Following a Michael addition/cyclocondensation with methylhydrazine, 4-fluoropyrazoles 91 are regioselectively formed (Scheme 32) [115]. Bouillon

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• indazoles would provide greater synthetic utility for this valuable heterocycle. These examples suggest a common intermediate such as methyl 5-bromo-1H-indazole-3-carboxylate (6) could be used to generate such compounds. An alkylation strategy that uses the vast array of commercially available alcohols as

• alcohols, react with 6 under different reaction conditions. In this paper, we report a concise and efficient approach to prepare N1- and N2-substituted analogs with high selectivity and excellent yields (>84%) from the same substrates: alcohols and 5-bromo-1H-indazole-3-carboxylate (6). Results and

• promising yield results of P1, we next explored the scope of this transformation using a variety of alcohols (13a–q, Table 3) and report their regioselectivity as determined by crude LC–MS. Sulfonates 14a–q were prepared as described above or purchased (see Supporting Information File 1). The subsequent

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

• were carried out using microwave activation. We then introduced various aromatic and aliphatic amines as well as alcohols and mercaptans into the reaction. In order to demonstrate the structural diversity of the compounds obtained, a wide range of diazotetramic acids 1 of different structures was used

• the lower stability of the less-substituted β-lactam derivatives under thermolysis conditions. Additional alkyl substituents sterically shield the ring and prevent an unwanted nucleophilic attack leading to product degradation. In reactions with alcohols and mercaptans, the corresponding esters 3k–n,r

• the exocyclic carbonyl group by preformed ring contraction and interaction of the intermediate ketene with the selected nucleophile. Various aromatic and aliphatic amines as well as alcohols and thiols can be used as nucleophiles. 5-Monosubstituted diazotetramic acids give exclusively trans

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• aldehydic component has been generated in situ through Fe3O4-mediated aerobic oxidation of benzyl alcohols. Magnetic nanoparticles were supported by Shaabani and Farhid on spent coffee ground and served also as catalyst for the GBB reaction, although the role of coffee ground was not clearly explained [33

• underwent cyclization and dehydration to produce linked polyheterocyclic indoles 75. The authors managed to prepare five adducts in 15–33% yield. Another mechanistic scenario occurred at higher temperature (Scheme 25, conditions b). The secondary amine of diol 73 substituted both secondary alcohols to