Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

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

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• to substitute the S atom and form adduct A. Adduct A underwent a decomposition by releasing a molecule of compound 2 [18]. The formed compound B underwent intramolecular cyclization followed by hydrolysis of the imide group with subsequent decarboxylation and formation of the intermediate C that was

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• transition metals, Lewis acids, and organocatalysts has been productively utilized in asymmetric transformations [7][8][9], cross-couplings [10][11][12], and oxidative decarboxylation reactions [13][14], among others. The use of a cocatalyst to control these photochemical transformations enables reactions

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• a few steps into (2S,5'S)-tricholomic acid [47]. The absolute configuration of (R)-(−)-carnitine was established by enzymatic decarboxylation of (2S,3R)-3-hydroxyglutamic acid followed by exhaustive methylation [121]. Fluoroglutamic acids are of special interest for PET imaging [122] and among other

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• is an unusual cofactor in that, even without the enzyme, it can catalyze many of these reactions [2]. For example, the decarboxylation of pyruvate in water can be accomplished by ThDP, but when it is bound to the enzyme pyruvate decarboxylase (PDC), the decarboxylation rate is increased by 12 orders

• the AP and IP forms are present in the resting enzyme [54] and decarboxylation, rather than formation of the first intermediate, was found to be rate limiting [60]. On the other hand, product release was the slowest step for ZmPDC and ScPDC [61], so clearly not all ThDP-dependent enzymes behave in the

Gold-catalyzed ethylene cyclopropanation

• Silvia G. Rull,
• Andrea Olmos and
• Pedro J. Pérez

Beilstein J. Org. Chem. 2019, 15, 67–71, doi:10.3762/bjoc.15.7

• ], electroreductive dehalogenation [7] and decarboxylation of diethyl 1,1-cyclopropyldicarboxylate [8]. Other methods include the transesterification of other alkyl cyclopropanecarboxylates [9] and the esterification with ethanol of the cyclopropanecarboxylic acid [10]. This product finds applications as lubricant

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• tetraketide intermediate that can be cyclised by aldol condensation, followed by elimination of water to result in the aromatic ring system. Thioester hydrolysis and decarboxylation produce 29a that can be converted by SAM-dependent O-methylation into 24. In summary, this hypothetical biosynthetic mechanism

Synthesis of unnatural α-amino esters using ethyl nitroacetate and condensation or cycloaddition reactions

• Glwadys Gagnot,
• Vincent Hervin,
• Eloi P. Coutant,
• Sarah Desmons,
• Racha Baatallah,
• Victor Monnot and
• Yves L. Janin

Beilstein J. Org. Chem. 2018, 14, 2846–2852, doi:10.3762/bjoc.14.263

• the corresponding α-nitro esters 6a–s. Isopropanol was used instead of ethanol in order to decrease the incidence of a recurrent side product arising from a decarboxylation or a retro condensation of the partially reduced ester function (this side product was characterized in 1H NMR by two triplets at

Synthesis of a tyrosinase inhibitor by consecutive ethenolysis and cross-metathesis of crude cashew nutshell liquid

• Jacqueline Pollini,
• Valentina Bragoni and
• Lukas J. Gooßen

Beilstein J. Org. Chem. 2018, 14, 2737–2744, doi:10.3762/bjoc.14.252

• anacardic acid (1) is even more attractive, because it contains an additional functional group. However, the separation and purification of this CNSL component without decarboxylation is laborious and relies on wasteful and tedious processes such as fractionate precipitation or column chromatography [6][17

• is added in excess. The main difficulty is that thermal purification of CNSL would inevitably lead to decarboxylation, and that unpurified CNSL, as it is obtained in an extraction process, contains a wealth of side components, many of which act as catalyst poisons. However, if an ethenolysis could be

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• -aminobenzoylacetyl-CoA (2-ABA-CoA) under decarboxylation [28][29]. In a next step, the pathway-specific thioesterase PqsE generates 2-aminobenzoylacetate (2-ABA) [29]. It has been shown, that also the broad-specificity thioesterase TesB present in P. aeruginosa can catalyse this reaction [29]. The quinolone core is

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• conditions led to the regioselective formation of 17-exo-heterocycles in good to excellent yields. The suppression of an acid-catalyzed thermal decarboxylation of the β-ketoester and thus a significant improvement in the yield of the desired heterocyclic products could be achieved by the preliminary

• (80 min). However, in addition to 6b (≈50%), the conventional, and even more the MW-promoted transformations led to a considerable amount (20–25%) of pregnenolone acetate (1) as a byproduct. The latter is thought to be produced by an acid-catalyzed thermal decarboxylation of 4 during the relatively

• synthesis of novel steroidal 17-exo-pyrazol-5'-ones from a β-ketoester precursor with arylhydrazine hydrochlorides has been developed. An acid-catalyzed thermal decarboxylation of the starting material as an unwanted side reaction could be avoided by applying a one-pot two-step protocol involving the in

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• decarboxylation, we planned to synthesize the alkyl-substituted tetramic core in one single step by Lacey–Dieckmann cyclisation of ethyl 2-(N-(4-methoxybenzyl)dodecanoylamino)acetate (9), although this compound does not contain an active methylene group. Thus, compound 5 was acylated with dodecanoyl chloride to

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• product 4a. Its treatment with a solution of sodium hydroxide in water promoted a quantitative lactone-opening/decarboxylation cascade sequence, yielding 2,4-dihydronaphthalene 6a in quantitative yield without the need of chromatographic purification. Interestingly, scaffold 6a is a valuable intermediate

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• . Naturally occurring amino acids, e.g., glycine, are often used in medicinal chemistry as linkers, structural components of scaffolds or even as precursors to useful building blocks. Wallentin and co-workers have described a method for the reductive decarboxylation of amino acids, using bis(4-chlorophenyl

• such a mild and selective oxidation. MacMillan and co-workers have recently developed a method for the bioconjugation of peptides by radical decarboxylation of the C-terminus of peptides and subsequent Giese-type addition to Michael acceptors. This is performed under blue light irradiation, using

Synthesis of pyrimido[1,6-a]quinoxalines via intermolecular trapping of thermally generated acyl(quinoxalin-2-yl)ketenes by Schiff bases

• Svetlana O. Kasatkina,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Ivan G. Mokrushin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2018, 14, 1734–1742, doi:10.3762/bjoc.14.147

• reaction (Table 1) was not detected. The most likely way of the formation of quinoxalinone 4a is hydration of the ketene with subsequent decarboxylation (Scheme 2); more careful drying the reaction vials and solvents easily reduced the amount of compound 4a. The formation of pyrido[1,2-a]quinoxaline 5a can

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• = COOEt); di-tert-butyl, R3 = COOt-Bu etc.) act as the most common dipolarophiles because of their high reactivity. Moreover, one or both carboxylate groups in position 3 and 4 in the final pyrazole are easily removable using a hydrolysis/decarboxylation protocol [5][16] thus giving pyrazole-4-carboxylic

• decarboxylation [16][95][96]. A novel strategy (Scheme 8) was recently developed by Harrity et al. (see entries 73, 74, 94, 117, 136, 137, 145–150 [32][33][34][82][89][91] in Table 4) who used trimethylsilyl acetylene as a dipolarophile. After regioselective cycloaddition giving 3-trimethylsilylpyrazole (cf. also

• example phenylpropiolic acid (R3: COOH) gives only minor a yield of the cycloaddition/decarboxylation product with 5,6-dihydro-3-hydroxy-4H-pyrrolo[1,2-c][1,2,3]oxadiazol-7-ium [97][98] (Scheme 9). The Table 5 again summarizes all the examples found, including reaction conditions from which we have come

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

• Gernot A. Eller,
• Gytė Vilkauskaitė,
• Algirdas Šačkus,
• Vytas Martynaitis,
• Ashenafi Damtew Mamuye,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2018, 14, 1287–1292, doi:10.3762/bjoc.14.110

• of 5-hydroxypyrazole-4-carboxylates in refluxing thionyl chloride. The obtained diesters can be transformed into the corresponding 4,4'-bipyrazoles via alkaline hydrolysis and subsequent decarboxylation. Detailed NMR spectroscopic investigations (1H, 13C, 15N) were undertaken with all products

• upon alkaline hydrolysis and subsequent decarboxylation (Scheme 7). According to the NMR spectra, compounds 10 are obviously present as 5-hydroxypyrazoles due to the absence of a proton attached to pyrazole C4. NMR spectroscopic investigation In Supporting Information File 1 the NMR spectroscopic data

Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent

• Elsa Deruer,
• Vincent Hamel,
• Samuel Blais and
• Sylvain Canesi

Beilstein J. Org. Chem. 2018, 14, 1203–1207, doi:10.3762/bjoc.14.101

• , decarboxylation, and fragmentation [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The sulfonate group is a useful functionality frequently employed as a leaving group in substitution reactions. Production of sulfonates [28] from alcohols generally involves reaction with a

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• involves the condensation of o-phthalaldehyde (27) with diethyl 1,3-acetonedicarboxylate (28), followed by hydrolysis and decarboxylation steps [46][47] (Scheme 5). Similar syntheses were made by Cook’s [48] and Föhlisch’s [49] groups. Nevertheless, for performing large-scale synthesis, the cost of 27 make

• structure of 86 was confirmed by the spectroscopic data. The formation of the heptafulvalenes could be explained via an intermolecular [2 + 2] cycloaddition product such as 87 between the carbonyl group of tropones and the ketene C=C double bond of 8-oxoheptafulvene (85) followed by decarboxylation. In a

• dehydrogenation using N-bromosuccinimide, and its properties were compared with those of benzotropolone 241A (Scheme 50) [178]. The benzotropolone 174 could also be prepared from diester 301 in a similar way (Scheme 50) [179]. The simultaneous hydrolysis and decarboxylation of benzotropolone-diester 304 to 174

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• electrophilic aromatic rings, non-acidic carbonyl groups, and suitable oxygen, nitrogen, and sulfur functionalities. Carbonyloxy radicals derived from typical hypervalent iodine(III) carboxylates by photolysis and other conditions [65][66][67][68] are known to undergo irreversible decarboxylation [69][70

• oxidation forming aryl ketones [52]. Note that the successful coupling of a range of secondary and tertiary carboxylic acids now supports the direct and selective C–H bond activation at the benzyl position by avoiding the formation of carbonyloxy radicals, which are susceptible to decarboxylation. In

Hypervalent iodine(III)-mediated decarboxylative acetoxylation at tertiary and benzylic carbon centers

• Kensuke Kiyokawa,
• Daichi Okumatsu and
• Satoshi Minakata

Beilstein J. Org. Chem. 2018, 14, 1046–1050, doi:10.3762/bjoc.14.92

• . Keywords: acetoxylation; carboxylic acids; decarboxylation; hypervalent iodine; iodine; Introduction The decarboxylative functionalization of carboxylic acids and the derivatives thereof is an important transformation in organic synthesis. In recent years, increasing efforts have been devoted to the

• development of decarboxylative transformations [1][2][3][4][5][6][7][8][9][10][11][12][13], especially through radical decarboxylation processes, allowing an easy access to valuable compounds from readily available carboxylic acids. However, despite these advances, the oxidative decarboxylation coupled with C

• most of the starting material was recovered (Table 1, entry 14). This result is consistent with a reaction proceeding via a light-induced radical decarboxylation process [21][25]. We next explored the scope of the decarboxylative acetoxylation reaction (Scheme 2). A variety of carboxylic acids

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• -methylbutyl acetate (29) and 2-methylbutyl acetate (32). The alcohol portion of these esters likely originates from leucine and isoleucine through transamination to the corresponding α-ketocarboxylic acid, oxidative decarboxylation and reduction. For the pentanoate and heptanoate esters not only the

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• ). However, it was found that the generation of the trifluoromethyl anion proceeds faster than the subsequent transfer of CF3 to the aromatic halide. Subsequently, the problem was solved by using a slow addition mode that adjusted the rate of decarboxylation step to the rate of the consumption of CF3 in the

• aromatic trifluoromethylation step. The attractive prospect of trifluoroacetate as the trifluoromethyl source for the preparation of trifluoromethylarenes prompted the investigation of the mechanism of this reaction. A mechanistic study indicated that CuCF3 was formed by decarboxylation of the

• as the CF3 source (Scheme 7). High temperature was required to accelerate the rate of the decarboxylation of CF3CO2K and the increased pressure occurred during the process, which brought problems under batch conditions. Buchwald and co-worker deal with it through combining flow chemistry. Under flow

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• are already defined. A third extension with malonyl-SCoA and methylation gives rise to intermediate C that can be released, e.g., by a thioesterase to the β-keto acid D, followed by spontaneous decarboxylation to 11a. Two structurally related molecules to 11a have been reported from endophytic

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• ]nonadienes (bisdioxines) 4. When arylamines are used as the nucleophiles under neutral conditions, decarboxylation occurs during the formation of bisdioxines 8. However, when water or alcohols are added to 3 under acidic conditions, bisdioxine-carboxylic acids and esters 10 and 11 are obtained. Acid

• in isolable enol intermediates of type 9 [18]. The carboxylate cannot form in the presence of an acid and therefore decarboxylation does not take place (17 → 18 → 10). The mono- and dicarboxylic acids 10 and 11 are stable and do not decarboxylate easily. However, aromatic amines carrying strongly

• decarboxylated tetraoxaadamantane can be obtained. It is noteworthy that, when a free carboxylic acid moiety is present in the bisdioxine, it is invariably lost during the tetraoxaadamantane formation. The decarboxylation is likely to take place in the acrylic acid moieties in the trioxanonadienes during the