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

• ketene dithioacetals [67] or β-ethylthio-β-indolyl-substituted α,β-unsaturated ketones [68], the cyclocondensation reaction of β-ethylthio-β-indolyl-substituted α,β-unsaturated ketones with hydrazines/hydroxylamine [69][70][71] and the tandem [5C + 1C/1N]-cycloaromatization of α-alkenoyl ketene

Electrochemical allylations in a deep eutectic solvent

• Sophia Taylor and
• Scott T. Handy

Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189

• constant current of 20 mA. With this promising start, several other aldehydes and two ketones were explored under the same reaction conditions (Table 2). A range of aromatic aldehydes worked well as well as one aliphatic aldehyde (Table 2, entry 13) and one alkenyl aldehyde (Table 2, entry 10), although

• the highly electron-rich dimethylaminobenzaldehyde (Table 2, entry 4) afforded only recovered starting material. Both ketones (Table 2, entries 11 and 12) failed to react and resulted in just recovered starting material. 4-Nitrobenzaldehyde (Table 2, entry 5) also failed to afford any allylation

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

• ) substituent in the meta-position [38][39][40][41][42][43]. For example, several methods based on the Michael condensation–oxidation sequence starting from α,β-unsaturated ketones have been described (Scheme 1B) [44][45][46][47][48][49][50]. Recently, several methods have been developed based on the

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• amides, coumarins, alicyclic ketones, β-ketophosphonates, α-nitroketones, curcumin, and barbituric acid derivatives [1][2][8][9]. We analyzed a number of Biginelli-type products and publications and concluded that Se-containing DHPMs among the rarest examples and, in addition to this, ketosulfones have

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

• were overcome by the addition–cyclocondensation of α,β-unsaturated ketones. Embedding 1,3-dipolar cycloadditions into a one-pot process has additionally been developed for concise syntheses of pyrazoles. The MCR strategy also allows for concatenating classical condensation-based methodology with modern

• starting from 3-aminocrotononitrile to yield pyrazole 28. The authors explicitly mention that aryl ketones do not transform using this method. Besides, the functionalization of 1,3-dicarbonyl compounds and their subsequent conversion into pyrazoles can be conducted in a one-pot fashion. For instance

• phosphane ligands is crucial for the selectivity in this reaction. Suzuki coupling can also serve for the functionalization of iodochromones 55, which, as α,β-unsaturated ketones, undergo ring opening under the reaction conditions, followed by Michael addition–cyclocondensation. Xie et al. devised a method

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

• ; Introduction Hydrazones represent an important class of organic compounds. They can be readily prepared through the condensation of hydrazine derivatives with aldehydes or ketones. They have found widespread applications in materials sciences and supramolecular chemistry [1][2][3][4][5]. Importantly, they are

• -methoxymethylpyrrolidine)hydrazones could be also key intermediates for the asymmetric synthesis of α-substituted aldehydes and ketones [18][19]. Interestingly, depending on the substitution pattern, the C=N bond can feature different electronic properties [20]. For instance, various hydrazones have been employed for the

• . documented the synthesis of 1H-indazoles 9 via the electrooxidative cyclization of (hetero)aromatic ketones-derived N-phenylhydrazones 8 (Scheme 3) [38]. In contrast with the above-mentioned works, the electrolysis was carried out in an undivided cell under galvanostatic conditions. High yields were obtained

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• Haszeldine et al. [49][100]. The reaction of individual E- or Z-isomer of 1,2-difluoroethylene and fluorinated ketones (Scheme 21) led to a mixture of stereoisomers in both cases, although for the E-isomer, about 70% of the product retained the starting configuration. Overall, (E)-1,2-difluoroethylene had

• ]-cycloaddition reaction of fluorinated ketones and aldehydes [49][100] were indicative of the fact that under photochemical conditions, this reaction is likely to be a stepwise process involving the formation of a biradical intermediate. Either (Z)- or (E)-1,2-difluoroethylene easily reacted with

• . Photochemical [2 + 2]-cycloaddition with fluorinated aldehydes and ketones gives access to a variety of fluorinated oxygen-containing heterocycles. We hope that this article will help chemists to utilize HFO-1132 and that this olefin will find applications as a useful synthon in organic chemistry. 1,2

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

• steroidal 17-ketones were first alkylated in the presence of the lithium derivative of ethyl propiolate. After stereoselective formation of the corresponding adduct, the triple bond was chemoselectively reduced under catalytic hydrogenation using 5% palladium on charcoal. As a final step, a p

• starting material (35%). 16-Spiropyrazoline steroids In 2009 Mernyák et al. described the synthesis of 16-spiropyrazolines from 16-methylene-13α-estrone derivatives via a 1,3-dipolar cycloaddition reaction between the methylene of α,β-unsaturated ketones 53a,b and the ylide produced from the

• stereocenter C-3 was not provided. The same research group later reported a method for synthesizing steroidal spiro 1,3-thiazolidin-4-one derivatives in a two-step process starting from α,β-unsaturated ketones [48]. Initially, steroidal iminophenyl compounds 85 were synthesized in yields ranging from 70% to 75

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

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• strategy is founded on the build and release of molecular strain and achieves a formal transposition of a methyl group. During light irradiation, 3-phenylazetidinols are forged as reaction intermediates, which readily undergo ring opening upon the addition of electron-deficient ketones or boronic acids

• subsequent ring-opening reactions. In this regard, we uncovered a novel entry to dioxolanes by intramolecular ring opening of azetidines using ketones and boronic acids. Results and Discussion Photocyclization We initiated our study by a systematic investigating of the Norrish–Yang cyclization for the

• was shown that subsequent ring opening can be triggered by the addition of electron-deficient ketones or boronic acids, which resembles a novel strategy for azetidinol desymmetrization. The nature of the protecting group was found to be critical for the two-step process to be effective, which resulted

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• semihydrogenation of alkynes to form Z-alkenes using a PEM reactor [31]. The Pd/C catalyst was essential for the reaction. They recently found that a PEM reactor with a Rh/C catalyst was effective for the stereoselective reduction of cyclic ketones [40]. Nagaki et al. reported the electrochemical deuteration of

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

• continuous flow system (Figure 26) [71]. The authors were able to demonstrate rapid benzylic fluorination of 13 substrates, requiring residence times below 30 min. The use of photoexcited aryl ketones was further expanded in 2016 by Lectka and co-workers who reported the use of 5-dibenzosuberenone as a

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

• 10.3762/bjoc.20.136 Abstract The enantioselective 1,4-addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones catalyzed by a cinchona alkaloid-derived primary amine–Brønsted acid composite is reported. Both enantiomers of the anticipated pyrazole derivatives were obtained in good to excellent

• yields (up to 97%) and high enantioselectivities (up to 98.5% ee) under mild reaction conditions. In addition, this protocol was further expanded to synthesize highly enantioenriched hybrid molecules bearing biologically relevant heterocycles. Keywords: α,β-unsaturated ketones; iminium catalysis

• [10][11][12][13][14][15][16][17][18][19][20][21]. Among the developed organocatalyzed enantioselective 1,4-addition reactions of pyrazolin-5-ones, the catalytic asymmetric reactions of pyrazolin-5-ones with α,β-unsaturated ketones are comparatively less studied. In 2009, Zhao’s group were the first

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

• enantioselectivity of the resultant product (Scheme 1). A one-pot oxidation–Cannizzaro reaction of aryl methyl ketones to mandelic acid derivatives was observed in the presences of ytterbium triflate as the catalyst. The intramolecular reaction sequence employed a SeO2/Yb(OTf)3 combination to affect the in-situ

• oxidation of the aryl methyl ketones 5 to the corresponding aryl glyoxal with concomitant rearrangement of the aryl glyoxal to the target α-hydroxycarboxylic acid derivatives 6, catalyzed by Yb(OTf)3. The simple process reflects the generality of the methodology with yields ranging from 78–99% as

• synthesized via the Cannizzaro reaction. Proposed catalytic cycle for the dehydrogenation of alcohols. Intramolecular Cannizzaro reaction of aryl glyoxal hydrates using TOX catalysts. Intramolecular Cannizzaro reaction of aryl methyl ketones using ytterbium triflate/selenium dioxide. Intramolecular Cannizzaro

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

• optimized or slightly modified conditions, cyclic secondary, and tertiary alkyl carboxylic acids were smoothly coupled with 1,1-diphenylethylene to give 3i–m. α,α′-Diarylated ketones serve as crucial building blocks in the construction of both natural and synthetic compounds with significant biological

• relevance. In 2022, Yu et al. [29] showcased a very mild procedure for the effective synthesis of α,α′-diarylated ketones (Scheme 2). Compared to previous procedures, this methodology was a significant improvement as it did not require an excessive amount of additives or high temperature. The methodology

• , Wang and co-workers [30] demonstrated the photomediated synthesis of γ,γ-difluoroallylic ketones by reacting trifluoromethyl alkenes and acids in the presence of PPh3 additive and iridium photocatalyst in basic medium (Scheme 3). This methodology was suitable for a wide range of carboxylic acids in the

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• undergo base-promoted Boulton–Katritzky rearrangement to appropriate 1,2,3-triazoles 4 (Scheme 1c). Based on the performed investigation a general approach to the preparation of corresponding terarylenes with a 3-hydroxy-4-pyranone unit was designed. Results and Discussion The starting ketones 1 were

• , t-BuNHNH2). Unfortunately, in this case interaction of ketones 1 with aforementioned hydrazines led only to a complex mixture of unidentified products. At the same time the use of benzhydrazide or semicarbazide in the similar condensation resulted in recovery of starting compounds 1. Further, in

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

• transformations, cementing their position as a go-to option for organic chemists. Based on our continued interest in iodine(III)-mediated chemistry, we have explored numerous strategies in oxidative transformations such as direct α-tosyloxylation of ketones [12][13][14], and the oxidation of enol esters [15][16

• ], to access α-functionalized ketones. We recently developed the oxidative contraction of 3,4-dihydropyranones to access polysubstituted γ-butyrolactones [17]. In 2015 we demonstrated that [hydroxy(tosyloxy)iodo]benzene (HTIB) could be used to convert chloro- and bromoalkenes into their corresponding α

• heterocyclic compounds [20][21][22]. Particularly dialkyl bromoketones have been utilized in natural product synthesis [23][24][25], also as a precursor to reactive oxyallyl cation intermediates [26][27][28], and for their photochemical reactions [29]. However, the direct halogenation of unsymmetrical ketones

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

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

• chromones, presumably due to the electron-donating character of the methoxy group and the lower electrophilicity of the chromone. But this trend was also not general. Similar yields were obtained for ketones (R3 = Me, Ph) or esters (R3 = OMe). Treatment of 2-(salicyloyl)furan 35a with iodine in the presence

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• using 5-amino-1-benzyl-3,3-dimethoxyindolin-2-one (1) [12] and benzyl isocyanide (4), as amine and isocyanide components, respectively. Different carboxylic acids 2 and aldehydes/ketones 3 were evaluated using ZnF2 as catalyst (10 mol %) and MeOH as the solvent (Scheme 2 and Figure 2). A library of α

• ]. Carboxylic acids 2 and aldehydes/ketones 3 used in the Ugi4CR. GI50 range plot against human solid tumor cell lines of investigated α-acetamide carboxamide isatin hybrids. Green most potent, yellow intermediate, red less potent. (A) Library of isatin-based α-acetamide carboxamide oxindole derivatives

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

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

• reaction of aryl vinyl ketones, leading to the synthesis of 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1-indanones. By changing the temperature and reaction time, it was possible to modulate the reactivity, allowing the synthesis of two distinct product classes (3-aryl-2-ethoxycarbonyl-1-indanones and

• may drive further structure–activity relationship studies to identify indanone targets of pharmacological interest. Conclusion In summary, we developed a simple and efficient methodology for the Nazarov reaction of aryl vinyl ketones, leading to 3-aryl-2-ethoxycarbonyl-1-indanones and 3-aryl-1

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

• aldehydes or ketones, undergo base-assisted condensation reactions with amines providing the corresponding imines. In the last step, the active manganese hydride complexes reduce the imine compounds and afford the desired alkylated amine products (Scheme 2B). Several well-defined manganese complexes have

• )phosphine ligand (PN3P) (Mn3) and studied N-methylation reactions in the presence of t-BuOK (20 mol %) at 120 °C for 24 h in toluene [36]. This catalytic system tolerated various functional groups, including nitro, ester, amide, and ketones and gave moderate to good yields (42–98%) of the mono-N-methylated

• , which leads to the formation of a considerable amount of waste [52][53][54]. The BH approach allows a sustainable way for building C–C bonds by coupling abundant and cheap alcohols with ketones, nitriles, esters, and amides [4]. C–C Bond formation via alkylation of ketones with alcohols Several

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• for the cyclization. Alternatively (Scheme 1B), isoxazolo[4,5-b]pyridines can be constructed via intramolecular cyclization of 4-(propargylamino)isoxazoles [21] or through reactions of 4-amino-5-benzoylisoxazoles with ketones or 1,3-dicarbonyl compounds [10][13]. These and some additional examples of

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

• derivatives were isolated with good yields (Scheme 1). Instead, in the Senadi et al. approach, 1-(3-amino)-1H-indol-2-yl)-1-ketones were obtained through a Pd(0)-catalyzed cascade process consisting of isonitrile insertion as carbon monoxide surrogate and a C–H cross-coupling [13]. The reaction took place in

• of indoles/CO/alkynes (alkynylcarboxylates) towards linear α,β-unsaturated ketones [72]. The reactions occurred in the presence of Pd(CH3CN)4(BF4)2/Xantphos as catalyst system under 20.7 bar of CO at 105 °C in THF. After 15 h, each reaction led selectively to the desired products (Scheme 40). More

• recently, Zhao and co-workers published a novel synthesis of indole-3-yl aryl ketones by a Pd-catalyzed direct carbonylation of the corresponding indoles with boronic acids [73]. The best catalyst was Pd(OAc)2 which catalyzed the reaction well in the presence of a base, such as KOH, in toluene as solvent

(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

• tetrasubstituted BCHs was recently reported by Shi and co-workers [82]. They employed Hantzsch esters as catalysts in the [2π + 2σ] cycloaddition of alkenes and bicyclobutanes. The synthesis of bicyclohexyl ketones by formal (3 + 2) cycloaddition of bicyclobutane and ketenes was recently reported by Studer and co