N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• ketone derivative 111, which was not isolated. After removal of the sulfinyl group under acidic conditions, and intramolecular N-alkylation upon treatment with sodium bicarbonate, (−)-pelletierine (112) was formed, and easily isolated as its hydrochloride derivative (Scheme 32) [120]. Compound 112 is a

• products were obtained after four additional steps: cross-metathesis of allylated compounds 120 with methyl vinyl ketone, reduction of conjugated C=C double bond, removal of the sulfinyl group under acidic conditions, and final stereoselective reduction of the imine formed by intramolecular cyclization

• (Scheme 33) [122]. The group of Prasad reported the diastereoselective synthesis of β-amino ketone derivatives from N-tert-butanesulfinyl imines and silyl enol ethers of aryl methyl ketone [123]. The synthetic interest in β-amino ketones was exemplified in the synthesis of alkaloid (+)-sedamine (125

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• Peter J. Halling WestCHEM, Dept Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland, UK 10.3762/bjoc.17.73 Abstract The kinetics of enzymatic desymmetrisation were analysed for the most common kinetic mechanisms: ternary complex ordered (prochiral ketone reduction); ping

• -pong second (ketone amination, diol esterification, desymmetrisation in the second half reaction); ping-pong first (diol ester hydrolysis) and ping-pong both (prochiral diacids). For plausible values of enzyme kinetic parameters, the product enantiomeric excess (ee) can decline substantially as the

• -reductases. The reductant (usually NADH or NADPH) has to bind first to the enzyme, followed by the prochiral ketone in the second step. The chiral products are then released before the oxidised co-product. “Ping-pong, second”. Followed by most transaminases and lipase or esterase-catalysed acylation of

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• condensation between ketone and formylquinoline. The amine and the intermediate A undergo Michael addition furnishing the keto-amine B. Further, an intramolecular cyclization with the attack of the amino group onto the carbonyl functionality with subsequent elimination of a water molecule results in the

• min). The protocol adroitly represents the efficiency of microwave and multicomponent strategy in the generation of complex molecules like steroids. The mechanism follows a pathway where an imine A is generated from the reaction between steroidal ketone and ammonium acetate. Simultaneously, the

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• corresponding ketone 10bc. Eventually, pyrrole derivative 10bc, having a carbonyl group, was obtained by these reactions (Scheme 7). In order to increase the conjugation of dibenzosuberenone 1 for the photophysical aspect, the p-quinone methide derivative of dibenzosuberenone 11 was synthesized according to the

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• substituent at the nitrogen atom also plays essentially no role for the diastereoselectivity of the cyclization (Table 3, entry 10 vs entry 9). The minor cis-diastereomer of N-(1-β-naphthylethyl)pyrrolidone 12j crystallized after oxidation to ketone 13j and its configuration was unequivocally established by X

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• with tosylhydrazone The first publication on the synthesis of methanofullerenes via tosyl derivatives appeared in 1993 [83]. According to the original source, C60 cyclopropanation is assumed to involve a diazo compound preliminarily synthesized from an aldehyde- or ketone-based tosylhydrazone. The

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• activation of the chain-linking group of the polymer (either an ester, carbonate, ketone or amide) toward the nucleophilic attack of the various solvents. Specific examples, broken down according to the nature of the polymer and the process, will be reported in the next sections, in which metal catalysts are

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• , ketone 2 (1.01 g, 99%) was isolated as white amorphous solid. [α]D20 +177.4 (c 0.46, CHCl3); 1H NMR (CDCl3, 400 MHz) δ 5.69 (d, J = 1.3 Hz, 1H), 4.45 (q, J = 3.0 Hz, 1H), 2.58–1.97 (m, 10H), 1.95 (dd, J = 14.4, 2.7 Hz, 1H), 1.85 (td, J = 13.5, 4.6 Hz, 1H), 1.73–1.58 (m, 1H), 1.52–1.47 (m, 1H), 1.46 (s

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• structure and/or degree of substitution at the C=C double bond. Thus, 1-phenylcyclohexene (1j, Table 2, entry 10), gave the epoxide 2j as the main product along with 19% of the corresponding allylic ketone in position 3 of the cyclohexenyl moiety (α-oxidation product). On the other hand, the epoxidation of

• the diene (±)-limonene (1k, Table 2, entry 11) took place mainly on the endocyclic C=C double bond with good selectivity, although with a relatively modest conversion. On the contrary, for cyclohexene (1l, Table 2, entry 12) the main oxidation product was found to be the corresponding allylic ketone

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• flash column chromatography, using a n-hexane/ethyl acetate mixture as eluent to yield the products 12a–o. General procedure for the synthesis of sulfones A solution of β-naphthyl-β-sulfanyl ketone (0.1 mmol) in 0.8 mL DCM was cooled to 0 °C. m-CPBA (0.22 mmol, 37.97 mg) was added to this stirred

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• ][70][71], but the use of HCF3 for this transformation reaction is still limited. In 1998, Russel and Roques examined the transformation of methyl benzoate to trifluoromethyl phenyl ketone with HCF3 in the presence of KHMDS or KH/DMSO in DMF, but the method required DMF and only a single example was

• indicated (Scheme 2a) [23]. Prakash and co-workers showed the first example of the DMF-free preparation of trifluoromethyl phenyl ketone with HCF3 in the presence of KHMDS in THF, but they did not examined the scope of the reaction (Scheme 2b) [38]. In 2018, Szymczak and co-workers showed a single example

• of the preparation of phenyl trifluoromethyl ketone using HCF3-derived borazine CF3– in 29% yield (Scheme 2c) [43]. Very recently, Han, Lian, and co-workers reported that a protocol using diisopropylaminosodium (NaDA) was useful for the trifluoromethylation of esters to trifluoromethyl ketones with

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• 5m compared to the longer chain substrates (e.g., 5c and 5l) could be explained mechanistically by the formation of a terminal carbocation upon the extraction of a fluorine atom by the aluminium species (Scheme 3). This carbocation could be stabilised to varying degrees by the ketone moiety

• ketone. When the 4-methoxy derivative 5n was treated with AlCl3 using our standard conditions, none of the expected 1,1-dichloroalkenone 6n was obtained. Instead, the acid chloride 13 was isolated in an excellent yield (Scheme 5). The structure of this product was elucidated using 2D-NMR experiments

• the described reactivity would be observed with substrates not containing a ketone linker. Replacing the ketone moiety with an oxygen or sulphur atom proved unsuccessful, with only complex mixtures being obtained the upon treatment with AlCl3 (see Supporting Information File 1). This observation

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• allylic carbenium ions could exist in solution. The solvolysis of CF3-substituted allyl sulfonates was thus thoroughly examined by Gassmann and Harrington [76]. The solvolysis of doubly CF3-deactivated 90 in trifluoroethanol (TFE) required the presence of 2,6-lutidine, leading to ketone 91 and triflate 92

• , Pittman, et al. investigated the protonation of a variety of trifluoromethyl ketones in a superacid [35][91]. Trifluoromethyl ketone protonation was observed by NMR spectroscopy at −60 °C in a superacidic FSO3H–SbF5–SO2 solution (Scheme 34). The 19F chemical shift variation for the generated oxygen

• ↔142’ (Scheme 35). Oxygen-stabilized α-(trifluoromethyl)carbenium ions (oxocarbenium ions) have been exploited for chemical synthesis [92][93][94]. Ketone 143a and ketoxime 143b undergo Friedel–Crafts reactions in the presence of Brønsted or Lewis acid to furnish the corresponding CF3-containing

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• -difluorocyclopropyl acetals 110 to form 2-aryl-3-fluorofurans 112 (Scheme 50) [99]. The reaction could proceed either via the intermediacy of the gem-difluorocyclopropyl ketone 111 (path a) or by the direct rearrangement of the protonated acetal (path b). Recently, the group of Amii has reported the conversion of 1

• imines 115, which led to alkylideneazetidines 116 (Scheme 52) [102]. The MgI2 acted as a Lewis acid and reducing agent, effecting the distal C–C bond cleavage in 113a to form an allenyl ketone, or an equivalent fluoro,iodo-enone species, either of which could then have added to the imine 115 and led to

• -fluoropyrroles 142 (Scheme 62) [113]. The reaction involved the gem-difluorocyclopropyl ketones 143 and nitriles 144. It was proposed that the protonation of the ketone with triflic acid led to a partial ring opening of the gem-difluorocyclopropyl ketone to generate a carbocation-like center that was stabilized

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• ethyl 2-(benzylthio)acetate (3a, 20% yield) and 1-(benzylthio)propan-2-one (4a, 44% yield) were obtained in a pure form by column chromatography (Table 1, entry 1). Interestingly, the formation of both an α-thio ester and an α-thio ketone, starting from ethyl acetoacetate and a sulfur source, was not

• chromatographed on silica gel, eluting with hexanes/EtOAc 99:1 to isolate the product 4 after combining the appropriate fractions. Minor fractions of the corresponding compound 3 were isolated in 6% to 17% yield. In addition, we employed acetylacetone (5) as a reagent to obtain an α-thio ketone (Scheme 2

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• hydrogenation occurred with high stereoselectivity producing a single diastereoisomer of 29. Then, the amide was treated with methyllithium at −78 °C to provide ketone 30 in 85% yield. Subsequently, the intramolecular Mannich reaction was carried out, leading to the desired alkaloid, via precursor 32. Ketone 30

• diastereoisomeric mixture, converted to ketone (±)-37 via methylene derivative (±)-36, in 63% over two steps (Scheme 5). Ketone (±)-37 was converted to alkenyl triflate (±)-38 after treatment with LDA at −78 °C, followed by the Comins reagent [47]. (±)-38 was subjected to palladium-catalyzed hydrogenation

• , where the axial proton in position 3 appears in δ 4.62 as a triplet of triplets, having coupling constants 11.0 and 6.4 Hz. Oxidation of (±)-41 with the TPAP-NMO system produced ketone (±)-42, a potential precursor to (±)-euphococcinine (2). Although being racemic, Ikeda's synthesis employed an

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• for the complete disappearance of the starting material). Moreover, besides the ketone 16 [53], formed as byproduct in the reaction with AgOTf, we observed the formation of many other unidentified compounds, reasonably either via side reactions of gold intermediates or the degradation of the starting

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• selectively attacked the C-8 ketone moiety of 47 to give alcohol 49 in β-configuration in 80% yield [32]. Chemoselective and stereoselective reduction of the C-9 ketone of 49 was accomplished by treatment with NaBH(OAc)3 [33] and produced 50 after a two-step synthesis. Removal of the sulfoximine group in 50

• -mediated conjugated addition of methyllithium to enone 59 in the presence of boron trifluoride ether [34][35] produced desired ketone 60 in 75% yield. The resultant ketone 60 was converted to waihoensene (16) in two steps. Palladium-catalyzed carboxylative trimethylenemethane cycloaddition In 1986, Trost

• ) were reported by Li’s group [42] and Zhai’s group [43] independently in 2017 (Scheme 6B and Scheme 6C). In Li’s synthesis, the common intermediate dienone 86 was subjected to a 1,1’-bis(diphenylphosphino)ferrocene-promoted [3 + 2] cycloaddition [41] with allenyl ketone 91 to give adduct 92a in 52

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• (Scheme 17c) [63]. Interestingly, they found some of their examples required the more strongly reducing photocatalyst Ir(ppy)3 to achieve high yields, although the reason for this is unclear. Jiang et al. continued to explore the reactivity landscape of CPAs and azaarenes, demonstrating that ketone 128

• transition metal Lewis acids 291a–e that can coordinate to ketone substrates and form chiral photoactive complexes 292, which in many cases act as the in situ generated photocatalyst (Scheme 48) [115]. They have recently developed an example using an indazole-based ligand [116] to add to their well

• enolisable ketone 293 is used, enolate complex 294 can be formed in the presence of base (Scheme 49a) [116]. The complex in this example is then proposed to proceed via an oxidative quenching cycle with bromo nitrile 295 to form α-cyano radicals 295• that then add to another molecule of 294

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• more electrophilic ketone carbonyls of compounds IV firstly. To overcome these issues, we examined the reaction of acylpyruvic acid (2a) with o-aminothiophenol (1a) in the presence of carbodiimides in various solvents (Table 1). Fortunately, in many cases we succeeded to detect the desired BTA 3a by

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• 10a,b were established from their analytical and spectral data. The ketene stetching (γC=C=O) was detected in the IR spectrum near 2090 cm−1 and the ring ketone stetching (γC=O) appeared at 1730 cm−1. The 1H NMR spectra of these compounds were very similar to those of the parent molecules but their

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• products 41–44 (Scheme 15). Chen and co-workers maintained that their reaction proceeded via HAT between the excited-state ketone and the C(sp3)–H-containing substrate. However, a PS TTET mechanism still could not be ruled out when Selectfluor® is present. That 9-fluorenone gave no reaction in Tan’s

• fluorination [46][205]. The selectivity for β- or γ-fluorination could be attributed to an interaction of the breaking C(sp3)–H bond and the neighboring ketone, which is part of the proposed 5- and 6-membered transition state, respectively. When the 5- and the 6-membered transition state is possible, the free

• ). Ideally, to achieve the best selectivity, the β- and the γ-position must be distinctive based on their geometric constraints. We note that the nature of the transition states in this ketone-directed C(sp3)–H fluorination (and the subsequent carbonyl-directed C–H fluorinations) is not well-characterized

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• not isolated but directly converted into the norbornadienyl trifluoromethyl ketone 3 (Scheme 1). The smooth [4 + 2] cycloaddition of 1a as compared to comparably harsh thermal conditions of other propyne ketiminium salts with an internal acetylenic bond reveals the activating influence of the CF3

• converted in two steps into cyclohexadienyl ketone 5-Ch by intentional hydrolysis followed by dehydrogenating aromatization leading to biphenyl-2-yl trifluoromethyl ketone 6. The latter product was more effectively prepared in a one-pot cycloaddition/hydrolysis/aromatization sequence. 1H NMR spectra of

• unpurified 1,4-cyclohexadien-1-iminium salt 4-Ch and 1,4-cyclohexadien-1-yl ketone 5-Ch indicated the presence of a minor byproduct. In the case of 5-Ch, obtained as an oil, the two components could not be separated by column chromatography; however, the 1H NMR spectrum suggested the cyclobutene structure 5

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• reaction/hydrolysis sequence. The use of the dithiane 80 protecting group was crucial for the following steps. Initial attempts of using a dioxolane protecting group for the C-1 ketone (instead of dithiane) led to an insurmountable difficulty of the selective hydrolysis of the dioxolane and acetonide

• cleavage afforded the methyl ketone 96. The cyclic hemiketal 97 was unstable at an elevated temperature (37 °C), with t1/2 = 48 h. Both the Jacobsen (10 steps, 24.4% yield) and the Koide syntheses (11 steps, 22.3% yield) are relatively efficient in terms of the length and overall yield. Syntheses of the C

• an alkynyl ketone to produce the required stereocenter. Of the syntheses to date, Jacobsen’s use of an asymmetric Cr(III)-catalyzed cycloaddition stands as the most efficient route, in terms of synthetic steps and low catalyst loading, to the (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran and the

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• cross-coupling reactions. A 4-fluoro-substituted phenacyl chloride as well as a bromomethyl 2-naphthyl ketone proved to be competent substrates as well, thus furnishing the corresponding imidazoles 3i/3i' and 3j in 67–87% yield. Conversely, a phenacyl halide decorated with an additional phenyl group at

• formed. The latter was indeed isolated as the main product (68% yield, Scheme 3). A plausible mechanism for the formation of the 2-aroylimidazoles 3/3' is depicted in Scheme 4. A key intermediate may be the in situ generated α-imino ketone 5. The latter is known to undergo dimerization to give 6 followed

• intermediate α-imino ketone undergoes when a solution in ChCl/urea is stirred at rt for 4 h in the presence of Et3N (3 equiv) as a base. These cyclizations proved to be relatively sensitive to the electronic properties of the starting phenacyl azides as they did not take place in the presence of strong