Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• ]. One study reported a reaction involving the asymmetric reduction of ketones using an achiral borane, denoted as B(p-HC6F4)3, paired with a chiral oxazoline, as depicted in Scheme 3 [28]. Remarkably, in this study, these FLPs demonstrated the capability to achieve high conversion rates and enantiomeric

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

• versatile method using decarbonylation of benzofuranone followed by oxidation, that produces only CO2 as a non-toxic side product, is considered less hazardous. Although decarboxylation of aldehydes, carboxylic acids, and ketones are well known, albeit using metal catalysts, decarboxylation methods for

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

• . For example, Liu and colleagues demonstrated the electrochemical oxidation of benzylic C–H bonds to ketones using tert-butyl hydroperoxide as the radical initiator [14]. This method was applied to functionalize bioactive molecules, with celestolide, ibuprofen methyl ester, and papaverine being

• > secondary. Functional groups such as silyloxy, amides, ethers, esters, enolizable ketones, and nitriles were found to be compatible with this transformation. Late-stage functionalization of different molecules was demonstrated; for example, the azidation of ibuprofen occurred preferentially at the secondary

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

• usefulness for the epoxidation of the β-CF3-α,β-unsaturated ketones [40], we applied this method at first for the epoxidation of 1b. However, contrary to our anticipation, only a total recovery of the substrate was observed, and further search for an oxidant reached the usage of a NaClO aqueous solution with

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

• ) [21] are known compounds and were prepared from the corresponding commercially available ketones by reaction with NaBH4 in EtOH or EtOH/THF 1:1. 1,1-Diphenylethanol (1i) is also a known compound and was prepared according to the reported procedure [29]. 9H-Fluoren-9-ol (1m) and triphenylmethanol (1n

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• proved ineffective in facilitating the Michael addition of bisthiomalonates to conjugated ketones, whereas DABCO enabled the formation of desired products under mild conditions [30]. However, reports of highly stereoselective protocols utilizing hydrogen bonding catalysis have mainly focused on

• , condensation reactions, including the formation of transient C=N bonds, are significantly promoted under ball milling conditions [12][13][14]. It is noteworthy that the application of primary amines for activating cyclic ketones under mechanochemical conditions remains largely unexplored [36]. We aim to fill

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

• (MCRs) are one-pot reactions that utilize three or more readily available starting materials [1][2][3][4]. Typically, MCRs use reactive functional groups such as ketones or aldehydes, carboxylic acids, amines, and isocyanides where these simple building blocks can be utilized to form large libraries of

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