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

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• oxidation, whereas in Nicewicz's report, the alkene is oxidized. This modification allows for a significantly larger reaction scope (Scheme 29). Terminal alkenes and several functional groups such as ethers (163), esters (165), ketones (166), nitriles (167), and enones (170) are tolerated. The

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• catalysed by copper(II) complex of ligand IV. Asymmetric aldol reactions of various aldehydes with ketones catalysed by compound IV. Supporting Information Supporting Information File 62: General information and experimental data of prepared compounds, copies of 1H and 13C NMR spectra and DFT calculations

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• , but the second fluorination step occurs only after reaction for several days. In the solid phase, mechanical milling of the diketone substrate with solid Selectfluor in the presence of sodium carbonate [13][14], and reaction of ketones with a strong base and an N–F reagent give rise to the

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• pharmaceutical and biological activities. Among indole derivatives, bis(indolyl)methanes (BIMs) are profoundly interesting, due to their wide range of pharmaceutical properties. The most common approach involves the electrophilic substitution of various aldehydes and ketones by indoles, utilizing either protic

• the corresponding BIMs in good to excellent yields (70–95%). It is important to mention that electron-withdrawing groups led to enhanced reaction rates and product yields, compared to their electron-donating substituents. However, aliphatic aldehydes and ketones displayed significantly lower

• , rendering this protocol applicable for the chemoselective conversion of aromatic aldehydes to corresponding bis(indolyl)methanes in the presence of aliphatic aldehydes and ketones [81]. The proposed reaction mechanism for this protocol is showcased in Scheme 5. At the beginning of the reaction, the bromide

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• type addition reactions (Scheme 4A). In 1991, Okada and co-workers reported the addition of alkyl radicals to α,β-unsaturated ketones, by subjecting NHPI esters to visible-light irradiation in the presence of the photocatalyst [Ru(bpy)3]Cl2 and the reductant 1-benzyl-1,4-dihydronicotinamide (BNAH) [37

• coupling of NHPI esters with aldehydes enabled by NHC catalysis [106]. The reaction proceeds with the catalyst NHC-1 at 60 °C and gives rise to ketones (Scheme 30A). The proposed mechanism begins with the reaction of benzaldehyde (143) and the NHC-catalyst 144 to form the neutral Breslow intermediate 145

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• other end of the IF core with electron-accepting moieties. An overview of general motifs targeted in this work is shown in Figure 1. Results and Discussion Synthesis The synthetic building blocks 1–8 used in this work are shown in Figure 2. The dione 1 and the ketones 4 and 6 were synthesized according

• therefore it was not possible to determine the purity of the product by this method. In an initial attempt to investigate other synthetic pathways to extended IF compounds, the reduced IF 29 was synthesized from IF dione 1 by a Wolff–Kishner reduction of the two ketones as shown in Scheme 6. Compound 29

• Hex group in 11) on the nitrogen atom in the pyrrole ring have an effect on the absorption in the visible spectrum of pyrrolo-annelated IF-DTF ketones. Interestingly, the absorption of the dihydropyrrole IF-DTF 9 is redshifted relative to that of the pyrrole IF-DTF 4, while the absorption does not

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• -Markovnikov addition, respectively. On the other hand, the hydration of an internal unsymmetrical alkyne can lead to the formation of the two possible regioisomeric ketones. The hydration reaction requires a catalytic species, able to polarize the alkyne triple bond to facilitate water attack. Initially, in

• acid, the conditions reported in entry 9 of Table 1 were chosen as reference for the study of the reactivity of different alkynes. For the internal alkyl(aryl)alkynes a regioselective hydration occurred, with the only generation of the corresponding aryl ketones, formed after the attack of water to the

• diphenylacetylene (1a), affording the corresponding ketones in high yields after 5 h. Otherwise, terminal alkynes generally showed higher reactivity compared to internal ones. For all the studied terminal alkynes, only ketone products (Markovnikov) were obtained, excluding the formation of the anti-Markovnikov ones

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• reductive cyclizations of o-nitrobenzoyl ketones [57][58], enamines [59][60], or isoxazoles [61]. The scope of these reductive cyclizations is limited by the availability of the necessary intermediates and has remained largely underexplored, especially with regard to 4-quinolones with long-chain

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• of fused ketones 34, eliminating the need for transition-metal catalysts or oxidants. The technique offered a broad substrate scope, remarkable selectivity, and simple reaction conditions. A plausible mechanism had been proposed for the photocatalytic decarboxylative [3 + 2]/[4 + 2] annulation, as

• nitroarenes 48 (Scheme 22). The protocol demonstrated excellent tolerance towards a wide range of reducible functional groups, including halogens (such as chlorine, bromine, and even iodine), aldehydes, ketones, carboxyl groups, and cyano groups. Iodination Alkyl iodide is considered to be the most reactive

• , the research groups of Chen and Wang demonstrated an elegant use of electrostatic contact to promote radical–radical cross-coupling between N-alkenoxypyridinium salts 52 and NaI, resulting in the formation of various α-iodo ketones 53 when exposed to visible light (Scheme 24) [47]. In the process, the

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• other derivatives in good yields [37] (Scheme 1). Later, Wu et al. described a diastereoselective 1,3-dipolar cycloaddition of trifluoroacetaldehyde hydrazones with α,β-ethenyl ketones to obtain polysubstituted pyrazolidines and pyrazolines. These reactions were carried out under two different sets of

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• ketones can result in a different kind of AMYs to address the issue. The reaction of trifluoromethyl ketones with glycine or α-substituted amino acids generated stabilized AMY 8 which underwent cycloaddition with maleimides to give 2-CF3-substituted pyrrolidines 9 in 50–76% yield (Scheme 5) [65]. Both the

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• photooxidation of polystyrene in the presence of FeCl3 as a radical source (Scheme 21a) [202]. A molar yield of 23% benzoyl small molecules was achieved. Reisner and co-workers employed a similar approach but using aromatic ketones as photocatalyst (Scheme 21b) [203]. Benzoic acid and other aromatic small