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

• ; f) Cs2CO3, MeOH; g) t-BuMe2SiCl, imidazole, DMF; h) NaIO4, KMnO4, then CH2N2, ether; i) TBAF; j) 6 M HCl. Synthesis of dimethyl ester of (2S,3R)-2 employing (1S)-2-exo-methoxyethoxyapocamphane-1-carboxylic acid as a chiral auxiliary. Reagents and conditions: a) PhSeCl, MeOH; b) H2C=CHCH2SnBu3, ether

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• -benzyloxyacylamide and a range of terminal alkenes. The products include hydroxamic acid derivatives with a long alkyl chain, aromatic and heteroaromatic cores, halogen residue, carboxylic acid moiety at the terminal relevant position for drug discovery. Moreover, an alternate preparation of the amino acid component

A tutorial review of stereoretentive olefin metathesis based on ruthenium dithiolate catalysts

• Daniel S. Müller,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2018, 14, 2999–3010, doi:10.3762/bjoc.14.279

• commercially available and very inexpensive (≈40 €/500 mL) [20]. Catalyst loadings of 3 to 5 mol % are typically required to obtain useful yields of the corresponding allylic alcohols. The cross metathesis with carboxylic acid 15 is particularly noteworthy as cyclometallated Z-selective ruthenium catalysts are

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

• the carboxylic acid result in 26, while reductive cleavage and methylation of the phenol give 25. The aldehyde 25 was commercially available and matched the natural product in terms of mass spectrum and retention time. Compound 25 was transformed into the corresponding methyl ester by treatment with

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• imino-carboxylic acid form likely evolves to its iminium-carboxylate form B [50]. This last intermediate involves the existence of two possible transition states for the cyclization of the imidazolidinone core of which one of them is favored by an intramolecular hydrogen bond (Scheme 5). This control is

Synthesis of mono-functionalized S-diazocines via intramolecular Baeyer–Mills reactions

• Miriam Schehr,
• Daniel Hugenbusch,
• Tobias Moje,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2018, 14, 2799–2804, doi:10.3762/bjoc.14.257

• functionalized with a carboxylic acid 4 or a benzyl alcohol 5 could not be obtained using the reductive azo coupling. For the benzyl alcohol 5 a variety of different, unidentified byproducts formed and in case of the carboxylic acid 4 only the starting material was retrieved. We now present a reliable one-pot

• hydroxylamine and subsequently in situ oxidized to the nitroso compound using iron(III) chloride. After addition of acetic acid the reaction was allowed to proceed for several hours at room temperature to form the azo bond. For the benzyl alcohol-functionalized S-diazocine 5, the carboxylic acid of the

• nπ* absorption maxima are in a range between 508 nm to 516 nm (for UV–vis spectra measured in acetone see Supporting Information File 1). The half-lives vary from 24.8 h to 6.7 d. For the carboxylic acid functionalized S-diazocine 4 the two isomers generated after irradiation with 405 nm could be

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow

• Clémentine Minozzi,
• Jean-Christophe Grenier-Petel,
• Shawn Parisien-Collette and
• Shawn K. Collins

Beilstein J. Org. Chem. 2018, 14, 2730–2736, doi:10.3762/bjoc.14.251

• anhydrides, which has also been previously reported by Stephenson and co-workers [33]. The carboxylic acid 10 was submitted to a flow protocol using the optimized Cu(tmp)(BINAP)BF4 catalyst, CBr4 (1 equiv) and 2,6-lutidine as base with a residence time of 20 min (Scheme 1). The anhydride derived from p

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• coordinates with two zinc atoms present in the active site of PSMA. The γ′-carboxylic acid of the DUPA ligand does not play a significant role in the interaction with the PSMA active site and hence exploited as a handle for the construction of peptidic spacer of bioconjugate 13. While designing the required

• peptide spacer [38] of 13 (Figure 2) for the tunnel, an eight-carbon amino acid such as 8-aminocaprylic acid has been covalently attached to the γ′-carboxylic acid of the DUPA ligand. This ensures the adequate distance between targeting ligand and peptidic spacer so that the specific binding to the

• chelating core through carboxylic acid of lysine and attachment of fluorescent probe via ε-amino group present in the lysine amino acid. Increased hydrophobicity due to the introduction of long chain amino acids, aromatic amino acids in the targeted ligand peptide conjugate 13 would decrease the solubility

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

• 10.3762/bjoc.14.236 Abstract Multistep syntheses of novel 17β-pyrazol-5'-ones in the Δ5-androstane series were efficiently carried out from pregnenolone acetate. A steroidal 17-carboxylic acid was first synthesized as a norpregnene precursor by the bromoform reaction and subsequent acetylation. Its CDI

• multistep sequence (Scheme 1). First compound 1 was converted to the 17β-carboxylic acid 2b by the bromoform reaction and subsequent acetylation according to well-known literature procedures [21][22][23]. After the activation of 2b with 1,1′-carbonyldiimidazole (CDI) as coupling reagent in THF, the

• %). Analogously, β-ketoester 4' could be obtained from pregnadienolone acetate 1' through a Δ5,16-carboxylic acid intermediate [23][26] under identical conditions albeit in disappointing low yield (33%) which is presumably caused by the decreased propensity of the conjugated carbonyl compound to react with the

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• -aminocoumarin (3). Treatment of 3 with either isonicotinyl chloride (n = 0) or 4-pyridylacetyl chloride (n = 1), generated by reacting the corresponding carboxylic acid with oxalyl chloride, in the presence of triethylamine provided the N-acyl-3-aminocoumarins 4 or 5, respectively. The analogs 9 and 10, which

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• into its corresponding carboxylic acid 4f. Conjugated alkenyl triflates 3g–i were also subjected to the reaction, and the desired carboxylic acids 4g–i were obtained in moderate-to-high yields. Furthermore, the seven-membered cyclic substrate 3j that was derived from cycloheptanone afforded its

• corresponding conjugated carboxylic acid 4j in 75% yield. The alkenyl triflate 3k prepared from the corresponding aldehyde was also carboxylated, and its corresponding product 4k was obtained in moderate yield. The catalyst CoI2(Me2phen) was also effective with sterically hindered aryl triflates: the

• acid derivatives. Diene 14a was converted into the corresponding carboxylic acid 15a in good yield. In addition, 1,4-dienes having cyclohexenyl and geminal diphenyl substituents (14b and 14c) produced their corresponding linear carboxylic acids 15b and 15c in 78% and 57% yields, respectively. Substrate

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• ][32][33][34]. Attempts at synthesizing one of these epoxides with the standard mCPBA epoxidation (Scheme 2) led exclusively to rearranged aldehyde 24, presumably promoted by the carboxylic acid byproduct of mCPBA. Unfortunately, attempts to remedy this by using buffered conditions only led to an mCPBA

Novel photochemical reactions of carbocyclic diazodiketones without elimination of nitrogen – a suitable way to N-hydrazonation of C–H-bonds

• Liudmila L. Rodina,
• Xenia V. Azarova,
• Jury J. Medvedev,
• Dmitrij V. Semenok and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2018, 14, 2250–2258, doi:10.3762/bjoc.14.200

• vacuum from the proper fractions (0.5–0.1 mm Hg). Cyclobutane-2-one carboxylic acid (4а) [46][47]. Yield 1.03 g (90%); mp 43–44.5 °C (distilled); bp 93.5–94 °C (0.2–0.1 mm Hg). It is noteworthy that acid 4а is a very hygroscopic compound which is easily hydrolyzed to produce glutaric acid. Photolysis of

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• bioconjugate 4 and the crude deprotected bioconjugate 5. HPLC spectra of the crude protected bioconjugate 15 and the deprotected bioconjugate 16. Competition experiment between alcohol and carboxylic acid. Reagents and conditions: (i) 4-phenylbutyl alcohol or 4-phenylbutanoic acid (2.0 equiv), BMT (2.0 equiv

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• tank T8 where it is mixed with the reaction mixture. The process stream can be further passed through separator S3 (adsorption column) packed with Celite. The reaction mixture can pass through reactor R8 packed with silica-supported carboxylic acid and maintained at 120 °C to obtain the product (S

An amine protecting group deprotectable under nearly neutral oxidative conditions

• Shahien Shahsavari,
• Chase McNamara,
• Mark Sylvester,
• Emily Bromley,
• Savannah Joslin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2018, 14, 1750–1757, doi:10.3762/bjoc.14.149

• carboxylic acid protection [19]. To further explore the use of the 1,3-dithiane function as protecting group in organic synthesis, here we report the results of our studies on the use of the dimethyl-1,3-dithian-2-ylmethoxycarbonyl (dM-Dmoc) group for amine protection (Scheme 1). Compared with the Dmoc group

• conditions (Table 1, entry 9). In the β-elimination step, when methanol was used as the solvent as in the general deprotection procedure, no reaction occurred even after stirring overnight. This might be caused by the more favoured deprotonation of the carboxylic acid group by potassium carbonate, which made

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• 238 417281 Haus der Technik e.V., Hollestr. 1, 45127 Essen, Germany, Fax: +49 201 1803269 10.3762/bjoc.14.138 Abstract The Mitsunobu reaction basically consists in the conversion of an alcohol into an ester under inversion of configuration, employing a carboxylic acid and a pair of two auxiliary

• . [26]. Assuming that the alcohol is sterically hindered and thus represents a relatively weak nucleophile, the deprotonated acidic partner, NuO−, can react with the phosphonium intermediate first to afford an intermediate Nu-O-PR’3. In the case where a carboxylic acid is used, Nu-O-PR’3 represents an

• , conveniently, mildly and on large-scale using Ph3P, with either DIAD or DEAD and a carboxylic acid in THF at either –50 °C or at room temperature”. Hence, several protected mono- and disaccharides, such as 1–4 (Scheme 3) were selectively esterified with simple benzoic acid to give 5–7 and 9, respectively. In

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• converted to the the carboxylic acid analogue 82 by treatment with sodium hydroxide in MeOH at ambient temperature. Finally, deprotection of Boc groups under standard conditions afforded the targeted organocatalyst 83. Magnetic nanoparticles (MNPs) due to their high surface area have been widely used as

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• plausible mechanism and transition-state model 27 for the formation of the major isomer through the attack of the carboxylic acid group to the ipso position of the naphthol ring from the less sterically hindered Re-face of the substrate 25. It is worth mentioning that very recently they have introduced a

• spirocyclization of naphthol carboxylic acid [34]. Later Birman et al. reported a new variation of a chiral I(V) reagent, namely 2-(o-iodoxyphenyl)oxazoline derivative 28 [35]. The reagent was applied to an asymmetric [4 + 2] Diels–Alder dimerization of phenolic derivatives 29 to construct tricyclic derivatives 30

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

• tropones and benzotropones [79]. The reaction of 4,5-benzotropone (11) and 8-oxoheptafulvene (85), prepared in situ via the reaction of cycloheptatriene-7-carboxylic acid chloride (84) with NEt3, afforded 3,4-benzoheptafulvalene 86 in 50% yield as fairly stable deep brown crystals (Scheme 15). The

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

• acids, such as propionic acid, cyclohexyl carboxylic acid, pivalic acid, and benzoic acid, were also possible by simply replacing PIDA with iodosobenzene (Scheme 3). Here, the addition of 3 Å molecular sieves was essential for removing water derived from the iodosobenzene and to suppress the benzylic

• intermediate (path A). Alternatively, the benzyl radical formed in situ couples with the iodanyl radical to give the pseudo halide, benzyl-λ3-iodane, which is more reactive to nucleophilic substitution by a carboxylic acid [77][78]. Another possible course of the reaction mechanism assumes the formation of a

• carboxylation by the iodosobenzene/NaBr system In a flame-dried two-necked round-bottomed flask, under nitrogen, iodosobenzene (132 mg, 0.6 mmol) and finely powdered sodium bromide (103 mg, 1.0 mmol) were subsequently added to a stirred solution of diphenylmethane (1h, 84 mg, 0.50 mmol) and the carboxylic acid

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• nicotinamide as shown in the Figure 4 (conjugate 5). Suckling et al. further demonstrated another structural analog of thiazotropsin conjugate 6, a heterocylic triamide containing thiazole carboxylic acid, which showed significant activity (MIC = 63 nM) against Trypanosoma brucei [55]. However, the authors

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

• lower than that of a non-cyclic 2i. Using this protocol, 1-adamantanecarboxylic acid was smoothly transformed into the corresponding acetate 2k. In addition to the reaction with respect to tertiary carbon centers, the present method was successfully applied to benzylic carboxylic acid derivatives. For

• (AcOI), which participates in the generation of RCO2I by reacting with a carboxylic acid 1. Meanwhile, RCO2I is directly generated along with AcOI when 4 reacts with I2. Subsequently, decarboxylative iodination of RCO2I under irradiation with visible light affords an alkyl iodide intermediate, which is

Polysubstituted ferrocenes as tunable redox mediators

• Sven D. Waniek,
• Jan Klett,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2018, 14, 1004–1015, doi:10.3762/bjoc.14.86

• carboxylic acid is also available via basic hydrolysis of ferrocenyl aryl ketones [61]. Together with the redox potentials of ferrocene, 1 and 2, the hitherto unknown electrochemical potentials of 3 and 4 should cover a wide potential range. This will meet the requirements of different substrates for the

2-Iodo-N-isopropyl-5-methoxybenzamide as a highly reactive and environmentally benign catalyst for alcohol oxidation

• Takayuki Yakura,
• Tomoya Fujiwara,
• Akihiro Yamada and
• Hisanori Nambu

Beilstein J. Org. Chem. 2018, 14, 971–978, doi:10.3762/bjoc.14.82

• trivalent iodine B. Aldehyde 31 is further oxidized with 30 with the assistance of A or C [67] to give carboxylic acid 26. Iodine B is re-oxidized with 30 to regenerate C. The oxidation proceeds at room temperature because of the fast oxidation of trivalent B to pentavalent C. Conclusion In summary, we have

• layers were acidified with 10% HCl and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give pure carboxylic acid 26. Structures of pentavalent iodine