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

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• preparation of thioesters, acyl disulfides, ketones, and amides starting from N-thiohydroxy succinimide esters (NTSEs) 1’’’, which can serve as the acylthiolating and acylating source (Scheme 32) [65]. First, they synthesized a series of N-thiohydroxy succinimide esters by treating potassium thiolates with N

• selectively transfer the acyl or acylthio moieties. Arylboronic acids 74 and amines 76 were suitable for the acyl transfer and led to ketones 78 and amides 80 as the desired products. While, Grignard reagents 75 and thiols 77 acted as soft nucleophiles and resulted in thioesters 79 and acyl disulfides 81

• pyrroles 83 contained higher HOMO orbital energies, and lower band gaps compared to the unsubstituted parent 2,5-diphenylpyrrole. Organocatalyzed sulfenylation by N-(sulfenyl)succinimides/phthalimides In 2004, direct sulfenylation of a series of aldehydes and ketones 84 with N-(phenylthio)phthalimide (14

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• , the O-protonated forms ArC(=OH+)CH=CHCCl3, which are then cyclized into the target CCl3-indanones. These cations have been studied experimentally by means of NMR spectroscopy in TfOH and theoretically by DFT calculations. Under the same superacidic conditions in TfOH, CCl3-hydroxy ketones (1-aryl

• -4,4,4-trichloro-3-hydroxybutan-1-ones; ArCOCH2CH(OH)CCl3) undergo dehydration to the corresponding CCl3-enones, which are further cyclized into CCl3-indanones. The yields of CCl3-indanones starting from CCl3-hydroxy ketones are up to 86% in TfOH at 80 °C within 3–18 h. Keywords: carbocations; enones

• calculations, and to study their intramolecular cyclization in triflic acid into the synthetically and medicinally relevant (see recent reviews [12][13][14][15][16][17][18]) indan-1-ones. Results and Discussion The synthesis of 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones (CCl3-hydroxy ketones) 1a–o was

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• explored as catalysts for the hydrosilylation of ketones. Besides the type of the ligand in the NHC–Cu(I) complex, the counter anions (BF4 and PF6) also influenced the catalytic activity. Furthermore, the cationic complexes were found to be more efficient than the neutral analogues under similar conditions

• . The hydrosilylation of aryl, alkyl, and cyclic ketones could be accomplished with excellent yields (Scheme 35) [48]. In 2011, Gawley and co-worker reported an excellent reactivity and enantioselectivity of a C2-symmetric NHC–Cu(I) complex for the catalytic hydrosilylation of a variety of carbonyl

• compounds, including diaryl- and dialkyl ketones and prochiral ketones, respectively (Scheme 36) [50]. Riant, Leyssens and co-workers investigated the mechanism of the hydrosilylation reaction of ketones using DFT, in situ FTIR, NMR, and kinetic methods [51][52]. The catalytic characteristics of sterically

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins

• Feng Chen,
• Xiu-Hua Xu,
• Zeng-Hao Chen,
• Yue Chen and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2023, 19, 1372–1378, doi:10.3762/bjoc.19.98

• ; Introduction Acyloins (also known as α-hydroxy ketones) are widely found as structural motif in natural products [1][2][3][4][5][6][7] and bioactive molecules [8][9][10][11] (Figure 1). They can also be used as building blocks in organic synthesis [12][13][14], involved in numerous transformations to other

• important functional groups such as dicarbonyls [15], diols [16], amino ketones [17] and so on. Recently, the introduction of a trifluoromethyl group into organic molecules has received great attention due to their wide applicability in medicinal [18][19] and materials [20][21] chemistry. The toxicological

• direct conversion of carboxylic acids to ketones is an important chemical transformation [31][32][33][34][35][36][37][38]. However, to the best of our knowledge, this protocol has not been used for the synthesis of fluoroalkylated ketones so far. Very recently, we have developed a visible-light-induced

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• oxidative alkylation of cyclic benzyl ethers with malonates or ketones. Oxygen is used as a terminal oxidant at atmospheric pressure. The key intermediate of this oxidative coupling reaction is benzyl alcohol intermediate C (Scheme 4) [52]. The generation of N–O radicals from NHPI in the presence of oxygen

• . Due to the challenges associated with the activation of C(sp3)–H bonds, this kind of activation strategy has received extensive attention. Huang et al. developed a Cu-catalyzed CDC of unactivated C(sp3)–H ethers with simple ketones under the synergistic effect of CuBr2 and pyrrolidine. By this route

• , tetrahydrofuran or tetrahydropyran can smoothly react with many methyl aryl ketones to obtain the desired coupling products (Scheme 6a) [54]. The mechanism of the dehydrogenation cross-coupling reaction may undergo a radical pathway. Initially, the tert-butoxy radical produced by the dissociation of t-BuOOH may

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• organoboron reagents were realized [12]. Also, in terms of suitable Michael acceptors as substrates, unsaturated ketones, aldehydes, esters, thioesters, amides, alkenyl heterocycles and enoyl heterocycles became viable for conjugate additions. The maturity and robustness of this methodology is documented by

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• significantly affect the C–H alkylation reaction and the reaction also proceeded well with hydrazones 13 obtained from aliphatic aldehydes or ketones. Based on mechanistic experiments and DFT calculations, the reaction presumably proceeds via a Cu–carbene migratory insertion (Scheme 4b). In the presence of CuI

• hydrolyzed to get the corresponding ketones. In 2018, Albéniz and group [99] reported the direct C3-arylation of pyridines with the help of bipy-6-OH as coordinating ligand under palladium catalysis (Scheme 29). In most of the cases the arylated pyridines 152 were obtained as mixtures of ortho-/meta-/para

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• stereoselective methodologies have been published that demonstrate the Cu- or Ni-catalyzed conjugate addition of organozincs to α,β-unsaturated ketones 14 followed by the reaction of the metal enolate with a nitroolefin (20) (Table 1) [30][31][32][33]. These reactions were facilitated by different ligand families

• nucleophile (R3Zn−) to the ketone with moderate yields but still good stereoselectivities (Scheme 9B). In 2018, Wang and co-workers extended the group of applicable electrophiles for the zinc enolate-based tandem reactions. Following the conjugate addition of Et2Zn to acyclic α,β-unsaturated ketones 41, they

• properties. In several cases the α-SCF3-substituted ketones 44 were isolated in good yields and enantioselectivities but with low diastereoselectivities. Even though no asymmetric catalyst was involved, Kawano et al. recently demonstrated an attractive one-pot procedure for preparing complex bicyclic and

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• ]. Based on its structure, many other inhibitors have been developed, such as vinyl sulfones, fluoromethyl ketones, and semicarbazides [8][9]. These inhibitors covalently bind to the nucleophilic thiol group of Cys234 in the active site of cathepsin C via a thioether bond. Phosphonates have been identified

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• a B‒O/B‒H transborylation in catalysis was the catalytic Midland reduction of propargylic ketones developed by Thomas to give enantioenriched propargylic alcohols (Scheme 10) [74]. The reaction was proposed to occur by enantioselective reduction of the propargylic ketone 42 by myrtanyl borane 43 to

• to give aldol-type products 61. Thomas reported the borane-catalysed diastereo- and enantioselective allylation of ketones with allenes and HBpin to give diastereo- and enantioenriched allylic alcohols, after workup (Scheme 15) [78]. The mechanism was investigated by single-turnover experiments and

• first example of Al‒O/B‒H exchange in catalysis was reported by Woodward, in the enantioselective catalytic hydroboration of ketones with HBcat as the terminal reductant (Scheme 23) [103]. A mixture of 1,1′-bi-2-naphthol (BINOL), 1,1'-binaphthalene-2,2'-dithiol (DTBH2), or 2-hydroxy-2'-mercapto-1,1

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• ]. Dihydrolimonene 25 was converted in 9 steps into compound 60 before subsequent RCM. As the authors knew G-I catalyst isomerizes β,γ-unsaturated ketones, G-II catalyst was chosen to produce bicyclic compound 61. Several additional steps were necessary to forge the last ring and obtain the core structure 63 of this

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• ; hydrozirconation; palladium catalysis; Schwartz's reagent; terpenes; Introduction Conjugated dienones are recurring structural motifs in natural products. Several biologically relevant compounds carry (2Ε,4E)-unsaturated ketones or the corresponding esters or amides. Selected examples are clifednamide H (1) which

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• synthesis by Taber that used dichromate as an oxidant [13] led to a less diastereoselective reaction furnishing the three ketones 9, 10, and 11 in a ratio of 36:2:5. The cis-conformation of the decalin backbone of 9 and 11 originates from the endo-selectivity of the Diels–Alder reaction and the boat

• the ratio of the minor diastereomers, the ketone mixture was treated with NaOMe, resulting in epimerization of 9, arriving at a 3:3:1 mixture of 9, 10, and 11. Unfortunately, a moderate amount of material was lost due to competing aldol reactions of the ketones. While compound 9 was epimerized to a

• concept proved to be difficult to achieve, but by optimization of different parameters of this Domino reaction, the required enantiomerically almost pure ketones 9–11 were obtained (Table 1). The Mannich reaction worked best using diisopropylammonium trifluoroacetate as the catalyst [22]. The isolation of

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• ) into cis-stilbene (62), via the dihydrodithiin intermediate 61 [58]. The addition of lithiated dihydrodithiins with aldehydes, epoxides or ketones are also all feasible, but sometimes require some more attention (Scheme 11). Palumbo and co-workers have found that substituted dithiins such as 50 can

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• reactions constitutes one of the main pillars of organic synthesis [1]. In this respect, the all-carbon Nazarov cyclization of divinyl ketones represents a direct method for the synthesis of five-membered carbocycles [2][3][4][5][6][7][8][9]. Variants of the Nazarov cyclization with substrates bearing one

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• organocatalyst forms hydrogen bonds with both H2O2 and cyclic ketones [66]. A chiral Brønsted acid was used as chirality source and activator of H2O2 for an asymmetric sulfoxidation reaction [67] (Scheme 4B). It is generally accepted that in asymmetric Brønsted acid catalysis the activation of both the

• the side process of their overoxidation to aldehydes or ketones. In another work, 3-acetoxyquinuclidine showed improved yields compared to unsubstituted quinuclidine in the α-functionalization of N-Boc-substituted secondary amines [108], showcasing an amine cation radical activity tuning by the

• –H2O2 system the adducts of H2O2 and ketones (perhydrates) can also be active oxidative species [51]. Dioxiranes formed from ketones and hydroperoxides are electrophilic oxygen transferring agents used in epoxidation (including asymmetric variants) [131][132], CH-hydroxylation, and other oxidation

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• cyclohexanone (as well as other cyclic ketones) which delivered spiro-annulated 2-benzoxepines (such as 2a) along with a minor byproduct 3a identified by 1H NMR as the product of formal insertion of the rhodium(II) carbene species into the O–H bond of cyclohexanone enol form. This minor byproduct, on heating at

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• aldol-type reactions, and reductive Mannich-type reactions using RhCl(PPh3)3 with Et2Zn [41][42][43][44][45][46][47]. The rhodium-catalyzed reductive aldol reaction of α,β-unsaturated esters with aldehydes or ketones gives aldol-type products in good to excellent yields (Scheme 1) [43][44]. In addition

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• , United Kingdom 10.3762/bjoc.18.151 Abstract The reactions of aromatic aldehydes and levoglucosenone promoted by methoxide gives bridged α,β-unsaturated ketones, formed by a series of oxa-Michael-initiated cascade reactions in yields of up to 91% (14 examples). A complex series of equilibria operate

• unreported mode of reaction between α,β-unsaturated ketones and aromatic aldehydes promoted by base. Results and Discussion The reactions of 1 with aromatic aldehydes and sodium methoxide in methanol were investigated at ambient and elevated temperatures (Table 1). In the reaction of benzaldehyde and 1 at 60

• bridged α,β-unsaturated ketones; however, these reactions do not involve initiation by an oxa-Michael addition [23][24]. The reaction between 1 and aromatic ketones under basic conditions is analogous to the well-known aldol/Michael cascade reaction observed between aldehydes and enolates giving di- and