Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• , D-53121 Bonn, Germany 10.3762/bjoc.16.71 Abstract A new, mild and efficient protocol for the synthesis of trifluoromethyl(indolyl)phenylmethanols by the reaction of indoles with a variety of aromatic fluoromethyl ketones in the presence of K2CO3 (15 mol %) and n-Bu4PBr (15 mol %) in water. The

• be synthesized by Friedel–Crafts hydroxyalkylation reactions of indoles with trifluoromethyl ketones in the presence of either Lewis/Bronsted acid catalysts. Bandini et al. reported the trifluoromethyl hydroxyalkylation of indoles catalyzed by an organic base 2-tert-butyl-1,1,3,3-tetramethylguanidine

• ketones were investigated, and the results are summarized in Table 2. Trifluoroacetophenones having a halogen substituent at the para-position of the phenyl ring such as p-F (2b), p-Cl (2c), and p-Br (2d) provided the corresponding trifluoro-1-(1H-indol-3-yl)ethan-1-ols 3b, 3c, and 3d in 97, 92 and 89

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• silyl ethers 89–92 (Scheme 18), thus showcasing the synergistic relationship between Pd and Cu catalysis [43]. Driven by the success of earlier results, the authors utilized 78 for reductive couplings between ketones 93 and imines 97 as electrophiles to form unsymmetrical 1,2-diols 94–96 and 1,2-amino

• alcohols 98–100, respectively. Palladium was no longer needed for these transformations. The scope of the reaction with ketones was not limited to diaryl species and aryl ketones participated in the reaction, including those with more hindered alkyl groups (Scheme 19) [44]. This discovery was followed by a

• -additions of cuprates derived from a silyllithium [47] to α,β-unsaturated ketones [48]. There was no effort made at that time to convert these reactions to the corresponding catalytic processes, rather, the accent was more towards using the silyl group introduced as a hydroxy group equivalent [49][50][51

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• dr values, including alkyl or halogen-substituted phenyl and 2-naphthyl ketones (Scheme 2). Unfortunately, phenylglyoxal monohydrates bearing strong electron-withdrawing groups were not compatible with the current conditions. X-ray analysis of aziridine 4a confirmed the absolute configuration of the

Efficient synthesis of 3,6,13,16-tetrasubstituted-tetrabenzo[a,d,j,m]coronenes by selective C–H/C–O arylations of anthraquinone derivatives

• Seiya Terai,
• Yuki Sato,
• Takuya Kochi and
• Fumitoshi Kakiuchi

Beilstein J. Org. Chem. 2020, 16, 544–550, doi:10.3762/bjoc.16.51

• ][21][22][23][24][25][26][27][28][29][30][31][32][33]. In the presence of ruthenium carbonyl phosphine complexes, the reaction of aromatic ketones possessing C–H bonds or C–OR (R = alkyl) bonds with arylboronates provided C–H or C–O arylation products [21][22][23][24][25][26][27][28][29][30][31][32][33

• introduction of two different aryl groups at the ortho-positions can be achieved by chemoselective C–O arylation of aromatic ketones possessing both C–H and C–O bonds and subsequent C–H arylation. We envisioned that the application of this strategy to the anthraquinone template would provide its derivatives

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• was developed during the last ten years based on new directions for nucleophilic substitution reactions proceeding via intermediate seleniranium cations 2 generated from thiaselenole 1. We have carried out new regioselective reactions of thiaselenole 1 with dithiocarbamates [31], ketones [37], thiols

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• ketones and furanyl ketones, for instance, with good yield. To explain the reaction outcome, the authors suggested that the [Cu(I)(dap)2]Cl catalyst acted as an electron shuttle between the halide derivative and the allylmetal reagent, precluding a direct electron transfer between the allylstannane and

• chlorides [20]. This ATRA reaction was carried out with various fluoroalkylsulfonyl chlorides, such as CFH2SO2Cl, CF2HSO2Cl, CF3SO2Cl, CF3CH2SO2Cl, and C4F9SO2Cl, electron-deficient alkenes, including α,β-unsaturated ketones, amides, esters, carboxylic acids, sulfones, and phosphonates (Scheme 4). In

• addition of a trifluoromethyl radical to silyl enol ethers derived from ketones using the same reaction conditions (Scheme 12) [28]. 1.3 Oxidation reactions In 2015, Bissember and co-workers used the Sauvage catalyst to generate an α-amino radical, which was used to perform the synthesis of annulated

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• trifluoromethylselenolated alkyne product could be isolated. After that, the same group studied the α-trifluoromethylselenolation of ketones and esters starting from the corresponding halides or diazoacetates (Scheme 4) [19][20]. Both methods led to the desired products with moderate to very good yields, and the reactions

• carbonyl compounds with [(bpy)CuSeCF3]2 by the group of Weng. Trifluoromethylselenolation of α,β-unsaturated ketones with [(bpy)CuSeCF3]2 by the group of Weng. Trifluoromethylselenolation of acid chlorides with [(bpy)CuSeCF3]2 by the group of Weng. Synthesis of 2-trifluoromethylselenylated benzofused

Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines

• Yana I. Sakhno,
• Maryna V. Murlykina,
• Oleksandr I. Zbruyev,
• Anton V. Kozyryev,
• Svetlana V. Shishkina,
• Dmytro Sysoiev,
• Vladimir I. Musatov,
• Sergey M. Desenko and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27

• α,β-unsaturated ketones [8][9][10][11] or via their multicomponent analogues. On the other hand, multicomponent reactions (MCRs) directly leading to tetrahydroazolopyrimidine heterocyclic systems have also been published [4][5][16][17][18][19][20][21][22][23][24]. In particular, multicomponent

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• , and Grignard reagents to Michael acceptors. In that respect, since the pioneering example reported by Alexakis and co-workers in 1993 [5], a wide range of cyclic and acyclic electron-deficient alkenes, such as α,β-unsaturated ketones, esters, nitriles, sulfones, or nitroolefines, was intensively

• . However, as depicted in Scheme 1, due to their stronger reactivity than that of usual esters or ketones, a competitive 1,2-addition to the carbonyl function of enals could occur, leading to the corresponding alcohol as a byproduct. Moreover, even if the 1,4-addition is favored, thanks to the copper/ligand

• , the acylimidazole moiety constituted a privileged surrogate of esters, amides, ketones, and aldehydes. Indeed, this peculiar function, which was readily accessible from the corresponding aldehydes or Weinreb amides, could be efficiently converted into a wide range of carbonyl derivatives, as depicted

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• reaction to achieve spirocyclic pyrrolocyclopentenone derivatives. Specifically, the KA2 reaction was envisaged taking into account cyclic ketones, to install a quaternary carbon atom carrying the required 1,6-enyne moiety for the subsequent Pauson–Khand reaction, thus achieving the corresponding tricylic

• spirocyclopentenone derivative, although in slightly lower yield as compared for the homologous ketone (Table 1, entry 5). No conversion to the KA2 adduct was achieved by using unsaturated or aromatic ketones (Table 1, entries 7 and 8, respectively), confirming an important role of the electronic content of the

• molecular platforms for the generation of high-quality small molecule collections, taking advantage of their three-dimensional shape and structural bias to develop lead compounds. The combination of multicomponent KA2 and Pauson–Khand reactions using representative cyclic ketones, allylamine and

The reaction of arylmethyl isocyanides and arylmethylamines with xanthate esters: a facile and unexpected synthesis of carbamothioates

• Narasimhamurthy Rajeev,
• Toreshettahally R. Swaroop,
• Ahmad I. Alrawashdeh,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Seegehalli M. Anil,
• Kuppalli R. Kiran,
• Chandra,
• Paris E. Georghiou,
• Kanchugarakoppal S. Rangappa and
• Maralinganadoddi P. Sadashiva

Beilstein J. Org. Chem. 2020, 16, 159–167, doi:10.3762/bjoc.16.18

• ], iron nanoparticle-catalyzed reactions of 2-naphthol with benzaldehyde and some of its derivatives with thiourea [22], isothiocyanato oxindoles with ketones [23], ammonium isothiocyanates with chalcones [24], and α-isothiocyanato esters with α-keto amides [25]. Among the synthetic methods available for

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• set of substrates 6–25 was prepared from dimethylphenylphosphine sulfide 4 (Table 1). All compounds were obtained in good yields, both from aldehydes and ketones. For aldehydes and unsymmetrically substituted ketones, the formation of the products as diastereomeric mixtures could be observed

• -hydroxyalkylphosphine sulfides (Table 2). As it turned out, the sulfides derived from aldehydes 7–9 and 11 failed to undergo a rearrangement (Table 2, entries 1–4). On the other hand, compounds derived from ketones 12, 14–17, and 20–25 underwent a ‘clean’ reaction under the conditions. However, instead of cyclization

• 1–5). On the other hand, most of the substrates derived from ketones 12–16 and 18–25 underwent intramolecular sulfur migration with the formation of mainly β-mercaptoalkylphosphine oxides in very good yields (Table 3, entries 6, 8–10, and 12–18). Only in the case of compounds 16 and 21, the

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• ][76][77], converting alkynes and alkenes to ketones [78], oxidizing alcohols to aldehydes [79][80], as well as in the direct α-hydroxylation of ketones [81]. Furthermore, it could also be used to realize oxidative C–C [82], C–N [83], and C–O [84] bond formations. However, to the best of our knowledge

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• of two equivalents of ICl, signals at 2.85–2.93 ppm, 3.96 ppm, and 4.36 ppm, in addition to the phenyl protons, were observed, without any evidence of 10 being present. Based on literature reports for α-iodo ketones [21][22], it was clear that the signal at 3.96 ppm corresponded to H-1 in 9. This was

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• asymmetric hydrogenation of ketones [22]. They showed that upon reduction with Raney nickel powder electrodes modified with (R,R)-(+)-tartaric acid, 2-hexanone 3 was converted to (S)-(+)-2-hexanol 4 with an average optical purity of 4%, whereas Raney nickel powder electrodes modified with (S,S)-(−)-tartaric

• catalyze the enantioselective hydrogenation of prochiral ketones 18. The prochiral ketones such as acetophenone, 1-tetralone and 1-indanone were reduced to their corresponding alcohols 20a, 20b and 20c, respectively, with moderate optical yields, with formation of (S) as major enantiomer (Scheme 5). After

• installation of an oxygen atom on one face, promoting the addition of CO2 from the other face, resulting in enantioenriched carboxylated product 29 after acidification (Scheme 10). The authors described similar results involving the asymmetric electrocarboxylation of other prochiral aromatic ketones in a

Synthesis of aryl-substituted thieno[3,2-b]thiophene derivatives and their use for N,S-heterotetracene construction

• Nadezhda S. Demina,
• Nikita A. Kazin,
• Nikolay A. Rasputin,
• Roman A. Irgashev and
• Gennady L. Rusinov

Beilstein J. Org. Chem. 2019, 15, 2678–2683, doi:10.3762/bjoc.15.261

• ketones were used to synthesize new N,S-heterotetracenes, namely 9H-thieno[2',3':4,5]thieno[3,2-b]indoles by their treatment with arylhydrazines in accordance with the Fischer indolization reaction. Keywords: Fiesselmann thiophene synthesis; Fischer indole synthesis; N,S-heteroacene; thieno[3,2-b

• ]thiophen-3(2H)-ones 4a–k after neutralization of the reaction mixture with a mineral acid. It should be noted that the obtained ketones 4 were more sensitive to the presence of acids than their benzo-annelated counterparts [17][18]: when an excess of a mineral acid was used, we observed a decrease in

• arylhydrazines 5b–d containing electron–acceptor substituents or electron–donor ones. There was no obvious change in the yields of compounds 6l–o (78–84%, Scheme 3), which may indicate that the starting ketones had a rather high reactivity. To confirm the structure of TTI derivatives 6, we attempted to grow

1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

• Vito A. Fiore,
• Chiara Freisler and
• Gerhard Maas

Beilstein J. Org. Chem. 2019, 15, 2603–2611, doi:10.3762/bjoc.15.253

• -catalyzed reactions of acetylenic ketones and esters with pinacolborane have been discussed [7][8]. The Michael addition of PPh3 at acetylenic carbonyl compounds generates phosphonium/vinyl anion intermediates which have been trapped with CH-, NH-, OH- and SH-acids [5]. In this manner, the 1:1:1 reaction of

• leading to butenolides occurs easily [17]. In contrast to acetylenic esters and ketones, acetylenic carboxamides have rarely been exposed to nucleophilic phosphanes in organocatalytic or stoichiometric reactions. Recently, we have reported on the synthesis and reactivity of N-triflylpropiolamides 1

• furnish the vinylphosphonium ion 6. These two steps have been proposed earlier for the formation of related betaines from acetylenic ketones and esters (see Introduction). A replacement of the N-phenyltriflamide group by the conjugate base of the active methylene compound followed by deprotonation of the

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• ligands that were obtained from readily available natural (1S)-β-pinene and (1S)-α-pinene [18]. We applied these ligands for the formation of the ruthenium complexes, which were successfully used as catalysts in asymmetric transfer hydrogenation of prochiral ketones. In continuation of our studies on the

Excited state dynamics for visible-light sensitization of a photochromic benzil-subsituted phenoxyl-imidazolyl radical complex

• Yoichi Kobayashi,
• Yukie Mamiya,
• Katsuya Mutoh,
• Hikaru Sotome,
• Masafumi Koga,
• Hiroshi Miyasaka and
• Jiro Abe

Beilstein J. Org. Chem. 2019, 15, 2369–2379, doi:10.3762/bjoc.15.229

• unit because aryl ketones have been widely used as visible-light photosensitizers [36]. While most of aryl ketones were used as triplet photosensitizers, the benzil unit in the present study acts as a singlet photosensitizer. The detail of the sensitization processes was investigated by wide ranges of

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• ketones with cyclopentadiene [1][2][3][4][5][6][7][8]. Most commonly encountered are pentafulvenes, although tria- [4][9][10][11][12], hepta- [9][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] and nonafulvenes have also been studied (Figure 1). Historically, fulvenes were of great

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• superacids or coordination by a Lewis superacid to produce a di- (tri- or higher) cationic species, the study of superelectrophilic activation became a very active area of research [11][12][13]. The acid-catalyzed condensation of ketones and aldehydes with aromatic compounds is known as the hydroxyalkylation

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• could be prepared from enantiomerically pure β-hydroxy ketones through β-hydroxy-directed carbonyl reduction following Evans’ [3] or Prasad’s [4][5][6][7][8][9][10][11] method. The Narasaka–Prasad reduction of a δ-hydroxy-β-keto esters derived from β-hydroxy esters [12][13][14][15][16][17][18][19][20

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• a mechanochemical process. Keywords: AZADO; Ertalyte®; green chemistry; mechanochemistry; NaOCl·5H2O; selective oxidation; TEMPO; Introduction The conversion of primary and secondary alcohols to the corresponding carbonyl compounds (aldehydes and ketones, respectively) is of such importance in

• synthetic route that can be scaled up to pilot and industrial levels. Results and Discussion Since the most commonly employed oxidizing agents are solid reagents, we decided to develop an efficient and eco-friendly process for the selective oxidation of alcohols to the corresponding aldehydes/ketones based

• 4-phenyl-2-butanol into benzylacetone in only 30 min (Scheme 6, ketone 11b). This protocol was successfully extended to other secondary alcohols to afford the corresponding ketones 11b–19b in high conversions and yields. The oxidation of sterically hindered secondary alcohols such as adamantan-2-ol

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• analogue SG-14 (2S,3S)-84 in inhibiting hSphK2. Sphingosine-1-phosphate (S1P) analogues (2S,3R)-89a and (2S,3R)-89b with 1,4- and 1,3-disubstituted benzene rings incorporated into the alkyl chain were obtained from aziridine ketones (2S,1'R)-90a and (2S,1'R)-90b (Scheme 23) readily prepared using Weinreb

• amide (2S,1'R)-18 which introduced the correct 2S configuration into the final product [73]. The highly stereoselective reduction of ketones 90a and 90b with a NaBH4/ZnCl2 mixture gave aziridine alcohols 91a and 91b having the required 3R configuration of the final product. The terminal hydroxymethyl

• )-6 was transformed into its higher homolog (2R,1'R)-188 employing Wittig olefination, the C=C bond reduction and Swern oxidation. The required alkyl chains were introduced by Grignard reagents and mixtures of diastereoisomeric alcohols were oxidized to ketones 189a–d. Catalytic hydrogenation allowed