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

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• (1H,3H)-dione) by refluxing with thionyl chloride [20][23]. However, the preparation of partially hydrogenated 5,10-dihydropyrimido[4,5-b]quinolinediones has been repeatedly reported by one-pot condensation of substituted anilines, aldehydes and barbituric acids, usually in protic solvents (alcohols

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

• preparing spiro α-methylene-β-lactones from different steroidal propargylic alcohols [13]. The procedure involves a one-pot Pd-catalyzed cyclocarbonylation of alkynols using 5 mol % of Pd(CH3CN)2Cl2 as a catalyst precursor and 30 mol % of 2-(dibutyl)phosphine-1-(2,6-diisopropylphenyl)-1H-imidazole as

• -Spirofuran steroids Intramolecular cyclization of alcohols with allenes is a common method for obtaining 17-spirodihydro-(2H)-furan-3-ones. In 2006, Jiang et al. utilized a known reaction sequence to construct the 17-spiro heterocycle 27 from the commercially available ethylene deltenone 24 [20][21]. In this

• (110a and 110b, respectively). These protected compounds were subjected to alkynylation using 4-THPO-1-butyne on the carbonyl group at C-17, yielding steroids 111. Subsequent catalytic hydrogenation of the triple bonds, followed by deprotection of the alcohols from their THP ether groups and oxidation

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• iodanes (NHIs) as suitable reagents for the mild oxidation of activated alcohols. Two different protocols, both involving activation by chloride additives, were used to synthesize benzylic ketones and aldehydes without overoxidation in up to 97% yield. Based on MS experiments an activated hydroxy(chloro

• )iodane is proposed as the reactive intermediate. Keywords: alcohol oxidation; hypervalent iodine; N-heterocycles; Introduction The oxidation of alcohols to aldehydes and ketones is an essential transformation in organic chemistry [1][2]. Generating aldehydes is particularly challenging as they are

• mild oxidation of primary and secondary benzylic alcohols to aldehydes and ketones as an alternative to λ5-iodanes. Results and Discussion Initially, we investigated a variety of pyrazole-, triazole-, and oxazole-substituted hydroxy-NHIs previously developed by our group [25]. However, none of them

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• were used as received, without further purification. Solvents and air-sensitive reagents were distilled under a dry nitrogen atmosphere. Dry THF was distilled from sodium benzophenone ketyl. A Nafion N115 film was acquired from FuelCell Store and a 20 wt % mixture in lower aliphatic alcohols and water

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

• nucleophiles, including water to give benzylic alcohols, or methanol to give methoxy products. Musacchio and co-workers reported a similar approach for benzylic fluorination (Figure 33) [84], which followed a similar mechanistic blueprint to that reported by the Doyle group. Using tert-butoxide radicals

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• Morita–Baylis–Hillman (MBH) adducts [20][21], we were interested in further utilizing (E)-2-arylidene-3-cyclohexenones that can be facilely synthesized from MBH alcohols to build functionalized molecules. Herein, we wish to report our preliminary study on a catalyst- and additive-free synthesis of 2

• study began with the preparation of the (E)-2-arylidene-3-cyclohexenones 2 via DMAP-catalyzed elimination reaction of 2-cyclohexenone-MBH alcohols 1 and di-tert-butyl dicarbonate [22] as depicted in Scheme 2. Starting materials 2 were prepared in moderate to high yields. Next, we chose (E)-2

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• rearrangement using benzonorbornadiene and the chiral natural compound (+)-camphene as bicyclic alkenes, selectfluor as an electrophilic fluorine source, and water and various alcohols as nucleophile sources. The structure of bicyclic oxy- and alkoxyfluorine compounds was determined by NMR and QTOF-MS analyses

• materials, supramolecular and bioactive compounds [13][14][15][16][17]. To the best of our knowledge, although the oxyfluorination of various olefins with water and alcohols is known in the literature [18][19][20][21][22][23][24][25][26], there is no systematic study on the oxyfluorination of bicyclic

• alkenes. We previously developed a dihomohalogenation method using selectfluor as an oxidant [27]. Herein, we synthesized bicyclic oxy- and alkoxyfluorine compounds using selectflour as an electrophilic fluorination reagent, water and various alcohols as an nucleophile. Results and Discussion In this

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• in subsequent reactions. Reddy and coworkers carried out the Cannizzaro reaction of aromatic aldehydes to the corresponding alcohols in high yields by crossed-Cannizzaro reactions employing solid-supported KF-Al2O3 as catalyst [26] under microwave irradiation using solvent-free conditions. The use of

• important in synthetic organic chemistry due to its ability to provide a convenient route for the synthesis of alcohols and carboxylic acids from aldehydes. This disproportionation reaction has evoked numerous developments and applications. The Cannizzaro reaction proved to be particularly valuable in cases

• alcohols 10. Excellent yields and enantioselectivities of the intramolecular Cannizzaro version were observed furnishing a wide range of alkyl and aryl mandelate esters 9 and 3 (Scheme 5). The asymmetric intramolecular Cannizzaro reaction of anhydrous phenylglyoxal (7a) with alcohols was envisaged by

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• radicals by activation of C–O bonds using visible-light photoredox catalysis offers a mild and environmentally benign approach to useful chemical transformations. Alcohols, carboxylic acids, anhydrides, xanthates, oxalates, N-phthalimides, and thiocarbonates are some examples of alkyl and acyl precursors

• photocatalytic and electrochemical deoxygenation of acids and alcohols has attracted significant attention as the strategic cleavage of the C–O bond is quite challenging and opens up new possibilities for constructing useful compounds [12][13][14]. The use of photogenerated carbon-centered radicals, such as acyl

• becomes significant. C(sp3)–O bonds are ubiquitous in nature and can be easily found in biochemical feedstocks, such as alcohols and acids. On the other hand, alcohols and acids are easily accessible. Although the starting materials are abundant, the C–O bond strength and the high redox potential impede

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• microbes, in the form of alcohols, ketones, lactones, and glycosides, and of these various forms, the oxo derivatives in particular have strong aroma and biological activity. Interestingly, in addition to being used routinely as flavorings and aromatic agents, sesquiterpene oxo derivatives also have

• (Scheme 1) [16]. As an alternative to deprotonation, the germacradienyl cation can be captured by water to yield the sesquiterpene alcohol hedycaryol, which is an important intermediate towards the synthesis of sesquiterpene alcohols [17]. The reprotonation of (R)-(+)-1 germacrene A or hedycaryol at the

• , whereas natural products from C are unknown and a few sesquiterpenes are known products of D. Similarly, in the case of hedycaryols, cation A-OH can undergo deprotonations to yield α-eudesmol [20], β-eudesmol [14], or γ-eudesmol [15]. Cation B-OH can potentially lead to alcohols by deprotonation or to

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• reactions allow the sustainable construction of C–C and C–N bonds using alcohols as hydrogen donors. In recent years, manganese complexes have been explored as efficient catalysts in these reactions. This review highlights the significant progress made in manganese-catalyzed C–C and C–N bond-formation

• reactions via hydrogen auto-transfer, emphasizing the importance of this methodology and manganese catalysts in sustainable synthesis strategies. Keywords: alcohols; alkylation; amines; borrowing hydrogen; hydrogen auto-transfer; manganese; Introduction The construction of C–C and C–N bonds is of utmost

• friendly and atom-economical process for C–C and C–N bond formations utilizing alcohol as an alkylating agent and hydrogen donor, producing water as the only side-product [6][7][8][9]. Notably, alcohols are inexpensive, abundant and can be obtained from biomass, which makes this method even more attractive

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

• ) and the corresponding urea derivatives as byproducts. In the middle of the same year, Wu’s group succeeded in using N-(2-bromobenzoyl)indoles in the reaction with alcohols and anilines to achieve a Pd-catalyzed diasteroselective carbonylative cyclodearomatization [62]. The synthesis proceeded best

• when the reaction was performed in the presence of 10 mol % of Pd(OAc)2 and dppp as catalyst system, Na2WO4∙2H2O (1 or 2 equiv) as base and an excess of nucleophile (alcohols or anilines) in toluene as reaction solvent under 5 bar of CO at 100 °C. Also, 20 mol % of LiBr were added as additive when

• alcohols were used as the nucleophiles (Scheme 32). About three years later, the same group developed a simple and efficient method to access CO-linked heterocyclic scaffolds by a Pd-catalyzed carbonylative cyclization of alkene–indole derivatives with 2-alkynylanilines and 2-alkynylphenols, in the

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• Passerini-tetrazole product. Then, the Swern oxidation [22][23][24], which is widely exploited and has a wide tolerance of functional groups, was used to convert the tetrazole containing alcohols to aldehydes, in particular for derivatives bearing convertible isocyanides. Most building blocks were well