Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• Markovnikov product (i.e. with the CF3O in the “internal” position) was predominant, whereas for the allylic alcohol derivatives, the anti-Markovnikov addition (i.e. with the CF3O in the “terminal” position) was predominant (2e vs 2g and 2h vs 2i). This could be rationalized by the electronic effect of the

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

• . If the in situ conversion of anti,syn-7a to anti,syn-7b follows the above ester alcohol exchange mechanism, employment of dibenzyl malonate should afford a single compound. This is actually the case and the expected dihydrofuran anti,syn-7c was obtained in 53% yield as a 98:2 diastereomer mixture

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

• dioxide; Introduction Electrochemical reduction of benzyl alcohol derivatives can induce reductive cleavage of a C(sp3)–O bond [1] at the benzylic position to generate the corresponding benzylic anion species. This protocol has been frequently applied to electrochemical carboxylation [2][3][4][5][6][7][8

• used as substrate, selective C–O bond cleavage, followed by fixation of carbon dioxide, occurred at the benzylic C(sp3)–O bond rather than the C(sp2)–O bond on the phenyl ring to give the corresponding diphenylacetic acid 2h in 45% yield. Not only a secondary alcohol but also a tertiary alcohol was

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

• -morpholinyl amido and benzophenone imino groups with LiAlH4 and NaBH4 afforded the corresponding syn-2-benzyl-1,3-amino alcohol 134 in 83% yield. In the case of the dimethylamide derivative, deprotection of benzophenone imine 128 with NH2OH·HCl followed by the LiAlH4 reduction gave rise to chiral syn-2-benzyl

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

• the potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis. Keywords: aziridination; electrochemistry; H-bond activation; hypervalent iodine; nitrene transfer; Introduction Hypervalent iodine reagents find widespread application in selective oxidation chemistry due to

• ), Koser’s reagent (PhI(OH)OTs), Zhdankin’s reagent (C6H4(o-COO)IN3, ABX), and Dess–Martin periodinane (DMP) – and find application in an array of synthetically important transformations including olefin difunctionalization, carbonyl desaturation, alcohol oxidation, and C–H functionalization [3][4

• described in some group-transfer schemes [23][24][25], and in particular, fluorinated alcohol solvents, such as 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), have been reported to enhance hypervalent iodine reactivity by providing a H-bonding solvent cluster that enhances the electrophilicity of the iodine

Synthesis and reactivity of the di(9-anthryl)methyl radical

• Tomohiko Nishiuchi,
• Kazuma Takahashi,
• Yuta Makihara and
• Takashi Kubo

Beilstein J. Org. Chem. 2024, 20, 2254–2260, doi:10.3762/bjoc.20.193

• to the DAntM radical is shown in Scheme 1. The alcohol precursor 3 was prepared via addition reaction of lithium reagent 2 to 10-mesitylanthracene-9-carbaldehyde (1) in moderate yield (59%). The generation of the DAntM radical was performed using stannous chloride dihydrate with hydrogen chloride in

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• condensation by introducing additional functional groups into the amine moiety (Figure 3). Substituted arylamines bearing alcohol (3ae), phenol (3ad), alkene (3bi), dimethyl acetal (3bj) functionality can be accessed in good yields. Reaction of 1,3-diketone 1a with a non-amidine type heterocyclic amine, 3

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• emulsions. The polystyrene particles were treated with sulfuric acid to form a surface layer of sulfonated polystyrene. These particles were then used to produce Pickering emulsions, which were transformed into large-pore structures when treated with an alcohol/water mixture [12]. Another method involves

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 ammonium acetate and the alcoholic solvent acted as N and C1 sources, respectively. The authors proposed the mechanism depicted in Scheme 10. The deprotonation of hydrazone 52 afforded anion 54 which underwent SET anodic oxidation to form radical 55. In parallel, an elusive oxidation of alcohol

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

• protecting group yielded the corresponding hydroxyalkynyl derivative 4. Subsequent Lindlar reduction resulted in the (Z)-alkene and a chemoselective tosylation of the primary alcohol led to the formation of tosylate 5. This intermediate underwent a stereospecific 4-exo cyclization upon exposure to iodine

• of 10% Pd/C and 5% Pd/CaCO3 yielded reduced compound 19. Cleavage of the THP group with Amberlist-15® resin and a final Jones oxidation of the primary alcohol to the carboxylic acid, led to cyclization with the 17β-OH group affording the lactone 20 in a moderate overall yield (Scheme 6). Biological

• androgenic activity. Poirier’s group reported two methodologies to prepare spiromorpholin-3-ones from a β-amino alcohol functionality [39]. Spiro compounds were synthesized starting from estrone, in which the phenol group was protected as a methoxymethyl ether. Then, the protected compound was subjected to

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

• and subsequent oxidation yielded aldehyde 18, a precursor for the intramolecular ring closure of the eight-membered ring. Upon treatment of 18 with BF3·Et2O, diastereoselective Prins cyclization of 18 proceeded to generate secondary alcohol 19. Subsequent one-pot treatment with (n-Bu)4NF·HF resulted

• secondary alcohol of 21, the utilization of another variant, MoBsc9 L110A, Y112R, generated through the directed evolution of MoBsc9, facilitated the optimal conversion in the corresponding oxidative allylic rearrangement to afford brassicicene I (9) in 64% yield. Further palladium-catalyzed allylic

• to the biosynthetic conversion of 9 into 11 (Scheme 2B), an α-hydroxylated ketone 25 with suitable protections of the C3 and C8 hydroxy groups was synthesized from 23 in one pot. Conversion of the secondary alcohol in 25 into triflate 26 enabled the alkenyl shift from C1 to C12 followed by

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

• )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

• -iodanes have drawbacks, in particular low solubility and moisture sensitivity [11]. Hypervalent iodine compounds in a lower oxidation state (λ3-iodanes), such as iodosobenzene (PhIO)n or phenyliodine(III) diacetate (PIDA) have been reported in alcohol oxidations but they often result in overoxidation to

• oxidation of the alcohol. Only small amounts of benzoic acid 4a’ were observed in all reactions with additional AlCl3, suggesting that the additive inhibits the previously observed overoxidation. Surprisingly AlCl3 activated the cyclic tetrazole iodane 1a but had almost no influence on the reactivity of the

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• cyanoborohydride as a mild reducing agent, and paraformaldehyde as a methylating agent [36]. Methanol can be used as the methylating reagent in other methods. Here, a palladium on carbon (Pd/C) catalyst processes the dehydrogenation of the alcohol to form the corresponding aldehyde. The subsequently formed imine

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

• alcohol, isopropyl alcohol, and toluene) increased the reactivity of MtCh509 relative to the aqueous system, representing the first solvent‑tolerant chitinase from Microbulbifer species and its potential applications in industrial processes [50]. rChi1602 exhibited maximal activity at 60 °C and over a

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

• optimisation campaign. The fluorinated alcohol HFIP was used to dissolve caesium fluoride allowing for the electrochemical benzylic fluorination by Fuchigami, Inagi and co-workers in 2021 (Figure 40) [98]. The HFIP/CsF system functioned as both a fluoride source and as supporting electrolyte, enabling the

• PEG and CsF. Electrochemical benzylic C(sp3)–H fluorination with caesium fluoride and fluorinated alcohol HFIP. Electrochemical secondary and tertiary benzylic C(sp3)–H fluorination. GF = graphite felt. DCE = 1,2-dichloroethane. Electrochemical primary benzylic C(sp3)–H fluorination of electron-poor

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

• benzonorbornadiene (1a), the reactions of benzonorbornadiene (1a) with selectfluor and 10 different alcohol derivatives were examined (Scheme 1). Under optimum conditions, fluoroalkoxy compounds 3a–j were obtained in excellent yields (91–98%) by the reaction of benzonorbornadiene (1a) with selectfluor and alcohols

• selectfluor and a carbocation is formed by bonding with fluorine. Subsequently, fluoroalkoxy compound 4 is formed by Wagner–Meerwein rearrangement followed by alcohol addition and deprotonation. Conclusion New bicyclic fluoroalkoxy compounds were synthesized by a molecular fluorine and metal-free methodology

• mmol of benzonorbornadiene (1a), 0.6 mmol of selectfluor, and 1.2 mmol alcohol in 2 mL of CH3CN at 90 °C for 2 h. Isolated yields. Oxyfluorination of (+)-camphene (1b) with selectfluor and alcohols. All reactions were carried out using 0.5 mmol of (+)-camphene, 0.6 mmol of selectfluor, and 1.2 mmol

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• , in this case, the formation of carbinolamine 6a becomes predominant (45%), despite a small quantity of N,O-aminal 5j (14%) is also produced, by virtue of the alcohol released from the starting acetal 4j. Probably, the higher water concentration in acetonitrile shifts the equilibrium in favour of 6a

• over the time (Scheme 4). Within our proposed catalytic cycle, when compound 4j is utilized, methanol is released, due to the presence of a dimethyl acetal residue. Therefore, using molecular sieves (MS 4 Å) little alcohol molecules, such as MeOH, can be potentially trapped, allowing the insertion of a

• more encumbered alcohol, such as benzyl alcohol, which is not sequestered by MS 4 Å. As a matter of fact, the new benzylated N,O-aminal 7 was successfully obtained in 70% isolated yield as the sole product (experiment D, Scheme 5). In this latter case, the benzyl alcohol presumably reacts with the

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

• synthetic tool for the construction of functionalized molecules. Dating back to the 19th century, this reaction, though initially used for the synthesis of an alcohol and acid functionality from aldehydes, has henceforth proven useful to generate diverse molecular entities using both intermolecular and

• aldehyde molecules, forming an alcohol and an acid [1][2][3][4]. Since its discovery in 1853, the Cannizzaro reaction has emerged as an important reaction in synthetic organic chemistry with intermolecular, crossed, and intramolecular versions as demonstrated by numerous applications. Notably, the

• produce a carboxylic acid (R1CO2H) and a primary alcohol (R1CH2OH). When a mixture of formaldehyde (HCHO) and a non-enolizable aldehyde (R1CHO) is treated with a strong base, the latter is preferentially reduced to the alcohol (R1CH2OH) while formaldehyde is oxidized to formic acid (HCO2H). Herein excess

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

• (Scheme 16). This one-pot strategy involved the reaction of xanthates formed in situ with electron-deficient alkenes under visible-light photoredox conditions in the presence of PPh3. This approach did not require multistep synthesis of starting materials. In addition, alcohol groups in polyols could be

• converted rather selectively in the order tertiary alcohol< secondary alcohol < primary alcohol. They also proposed a mechanism, which is outlined in Scheme 16. The first step involves deprotonation of alcohol in the presence of base and nucleophilic attack of CS2 to generate a xanthate salt intermediate

• , functionalization of alcohols is required, which requires an additional step. Therefore, it is quite interesting to directly employ alcohols for creating carbon-centered radicals that facilitate photomediated organic transformations. In this section, we will discuss some methods where alcohol C–O bonds were

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• implies that protonation and cyclization may be concerted for that conformer (Figure S4, Supporting Information File 1). We previously transformed 2 into the trans,trans-6/6/6-tricyclic C6 alcohol 8 using mCPBA to epoxidize the C6–C7 alkene [7]. Under the same conditions, epoxidation of 1 yielded the 6,7

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

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

• alcohol and oxidation of the latter resulted in formation of the final product. The reason for the change of the regioselectivity of cyclization, as compared to the formation of products 36, remains unclear at present. The reaction of 3-halochromones with 3H-indole-2-thiones (thiooxindoles) 38a–c afforded

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

• in a terpene hydrocarbon, or through nucleophilic water attack, yielding a terpene alcohol [5]. To date, about 80,000 terpenes and terpenoids have been discovered [3], approx. 10% of which are sesquiterpenes, composed of 15-carbon skeletons [6][7]. Sesquiterpenes are mainly distributed in plants and

• (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

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• synthesis has been reported for several transformations, such as epoxide opening [56], ketal formation and deprotection [57][58], Mannich reaction [59], intramolecular Sakurai cyclization [60], alcohol oxidation [61], aromatic hydrocarbon nitration [62], imine allylation [63], Knoevenagel condensation [64

• according to well-established protocols [71][72][73][74]. The β-ketoesters were obtained employing a sequence of two reactions, the formation of the benzylic alcohol derivative, through a Reformatsky reaction using In(0), followed by a pyridinium chlorochromate (PCC) oxidation, giving the β-ketoesters 7a–g

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

• 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

• to the scientific community [10][11][12]. In this process, first, the metal-catalyzed dehydrogenation of the alcohol provides a reactive substrate for coupling with nucleophiles and the active metal hydride species. Later, the borrowed hydrogen is used in the final step to reduce unsaturated

• synthesis of amines and imines using Mn-pincer catalyst [37]. When t-BuOK (1 equiv) was used as a base, alkylated amine products were observed selectively using alcohol as an alkylating agent, whereas when t-BuONa (1.5 equiv) was used as base, alkylated imine products were isolated (Scheme 6). This

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

• phosphinic acid 7 was further protected with benzyl alcohol by a procedure adopted from reference [67] using TBTU and Et3N in refluxing dichloroethane. Compound 8 was obtained in 65% yield after silica gel column chromatography. To synthesise a nucleobase for nucleosides Va and Vb, we first obtained

• dichlorophosphane 9 from commercially available PCl3 and ethyl vinyl ether using a previously published procedure [68]. Compound 9 reacted with 1 equiv of benzyl alcohol in absolute Et2O and pyridine at −78 °C, followed by quenching of the reaction mixture with H2O. This procedure provided phosphinate 10 in more