Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• steps without purification of the intermediates. In this strategy, three different diversity sites could be generated, i.e., those derived from the isocyano and aldehyde components and a third one from the carboxylic acid used in the last acylation step. We sought to incorporate aryl or vinyl carboxylic

• acids to allow the subsequent reaction with alkynes based on the C(sp2)–H activation of these aryl or vinyl moieties. As depicted in Table 1, we chose the tetrazolic substrate 1a for the optimization of the catalytic addition of diphenylacetylene (3a), a process involving the metal-catalyzed ortho-C–H

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• ]thiophene core. The structures of “thiophenylated” DAEs AsTh1, AsTh2, SyTh1, SyTh2, AsOTh1, AsOTh2, SyOTh1, and SyOTh2 prepared and studied in this work are given in Figure 1. Methyl esters of the thiophene carboxylic acids were chosen as model building blocks, because they possess optical properties

• similar to the free acids. The future promising candidates which were expected to emerge in the course of synthesis and screening could be eventually transformed to the corresponding carboxylic acids possessing higher solubility in aqueous buffers and reactive groups required for bioconjugation. Results

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

• , Xu’s group [49] presented the palladium-catalyzed direct fluorination of unactivated C(sp3)–H bonds at the β-position of carboxylic acids with NFSI (Scheme 12). To achieve this transformation, an 8-aminoquinoline-derived auxiliary was developed as an effective directing group for the activation of the

• C–H bonds. In this transformation the presence of Ag2O and pivalic acid was found to be crucial for the successful synthesis of β-fluorinated carboxylic acids. Recently, the first example of a Pd-catalyzed protocol for the general enantioselective electrophilic C(sp3)–H fluorination of benzaldehyde

• decarboxylative trifluoromethylation of various primary and secondary aliphatic carboxylic acids. With AgNO3 as a catalyst, (bpy)Cu(CF3)3 (bpy = 2,2’-bipyridine) as a CF3 source and K2S2O8 as an oxidant, aliphatic carboxylic acids were converted to the corresponding trifluoromethylated products in good yields

A metal-free approach for the synthesis of amides/esters with pyridinium salts of phenacyl bromides via oxidative C–C bond cleavage

• Kesari Lakshmi Manasa,
• Yellaiah Tangella,
• Namballa Hari Krishna and
• Mallika Alvala

Beilstein J. Org. Chem. 2019, 15, 1864–1871, doi:10.3762/bjoc.15.182

• chemistry. The occurrence of an amide and/or ester bond is widely realized in organic molecules, proteins, natural products, pharmaceuticals, polymers and agrochemicals [1][2][3][4][5]. The conventional synthesis of amides involves the reaction of carboxylic acids or their derivatives such as acyl halides

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Enantioselective PCCP Brønsted acid-catalyzed aza-Piancatelli rearrangement

• Gabrielle R. Hammersley,
• Meghan F. Nichol,
• Helena C. Steffens,
• Jose M. Delgado,
• Gesine K. Veits and
• Javier Read de Alaniz

Beilstein J. Org. Chem. 2019, 15, 1569–1574, doi:10.3762/bjoc.15.160

• -Piancatelli reaction. Asymmetric aza-Piancatelli rearrangement with a range of substituted anilines. *To simplify the purification process, carboxylic acids were transformed in situ into the corresponding methyl ester using (trimethylsilyl)diazomethane. Asymmetric aza-Piancatelli rearrangement with a range of

• substituted furylcarbinols. *To simplify the purification process, carboxylic acids were transformed in situ into the corresponding methyl ester using (trimethylsilyl)diazomethane. Initial optimization studies. Supporting Information Supporting Information File 226: Experimental part and copies of NMR

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• available starting materials including scaffold diversity. A small focused compound library of 23 Ugi products was created and screened for antibacterial activity. Keywords: antibacterial activity; Doebner reaction; pyrazolo[3,4-b]pyridine carboxylic acids; Ugi reaction; Introduction Modern medicinal

• diversity-oriented synthetic (DOS) approaches. First, by using CBD and MCR strategies in a Doebner-type reaction we synthesized pyrazolopyridine carboxylic acids which were subsequently applied in the Ugi reaction, thus, combining two multicomponent procedures. Results and Discussion As mentioned above, the

• and to synthetize heteroaromatic carboxylic acids 4 and 7 starting from the same reactants but using a multicomponent and a sequential protocol. We chose these heterocyclic acids to be subjected to the further Ugi transformation based on their higher stability compared to other azoloazine carboxylic

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• groups on Ugi-4CRs with spirostanic, androstanic, pregnanic and cholestanic carboxylic acids, later on Chowdhury and co-workers published a similar strategy for the multicomponent derivatization of cholestanes using microwave assisted Ugi-4CR [27]. 2.1.3 Steroids as the isocyanide component: To our

• the 1,4-dihydropyridine scaffold. As depicted in Scheme 14, compound 46 was later subjected to a variety of post-MCR cyclizations, including the reaction with carboxylic acids to form the fused steroidal pyridopyrimidinones 47 and with carbon disulfide to form pyridopyrimidinedithione 48 in very good

• shown in Scheme 17, amino steroids could be reacted in MeOH or MeOH/CH2Cl2 at room temperature with peptide carboxylic acids and isocyanopeptides to furnish peptide–steroid conjugates such as 58 and 59. Interestingly, the same solution-phase protocol proved to be equally effective for the conjugation of

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• carboxylic acids, allowing direct coupling of haptens to the carrier protein. Hapten conjugation reaction with carrier proteins BSA and KLH Test reactions on submilligram scale (0.1 mg hapten:0.1 mg BSA, 1 mg/mL protein) were performed with activated HF-1 and BSA, resulting in a moderate number of haptens

• , copy number for the individual heroin and fentanyl haptens were 7.3 and 12.4, respectively. Another trend observed for the chemically contiguous haptens was the increased amount of time needed to activate the carboxylic acids. Typically, fentanyl and heroin haptens reach optimal threshold activation

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• ester group present in these compounds allows the obtention of carboxylic acids that can be further used in consecutive IMCRs. Furthermore, optically active isocyanoacetates can be easily obtained from natural amino acids. Recently, Dömling et al. [19] used this efficient approach in the synthesis of

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• stearic acid (3a) in the presence of amines such as pyridine or tributylamine. However, the analysis of the reaction mixture only showed unreacted starting materials. In previous work, an acceleration of the oxirane ring-opening reaction with carboxylic acids [34] or alcohols [35] by using Lewis acid

• -opening reaction of 2 with stearic acid (3a) was evaluated (Scheme 3a). Specifically, we focused on the use of Jacobsen cobalt(II)-salen complex (S,S)-cat (Scheme 3b), since similar salen complexes had originally been reported to facilitate epoxide ring-opening reactions with carboxylic acids as

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• -trisubstituted 2H-furo[2,3-c]pyrazole-5-carboxylic acids and related carboxamides [11][12]. The aforementioned carboxylic acids have been prepared by bromination of the corresponding pyrano[2,3-c]pyrazol-6(1H)-one derivatives followed by heating of the obtained 5-bromo derivatives in the presence of sodium

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• Institute of Engineering Science and Technology, Shibpur, PO-Botanic Garden, Howrah-711 103 (WB), India 10.3762/bjoc.15.61 Abstract The LANCA three-component reaction of lithiated alkoxyallenes LA, nitriles N and carboxylic acids CA leads to β-ketoenamides KE in good to excellent yields. The scope of this

• reaction is very broad and almost all types of nitriles and carboxylic acids have successfully been used. The alkoxy group introduced via the allene component is also variable and hence the subsequent transformation of this substituent into a hydroxy group can be performed under different conditions

• . Enantiopure nitriles or carboxylic acids can also be employed leading to chiral KE with high enantiopurity and dinitriles or dicarboxylic acids also lead to the expected bis-β-ketoenamides. β-Ketoenamides incorporate a unique combination of functional groups and hence a manifold of subsequent reactions to

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• –H bonds (≈80–90 kcal/mol) make selective functionalization possible [1][2]. The installation of oxygen functionality at benzylic C–H bonds allows for the production of benzylic alcohols, aryl ketones, and aryl carboxylic acids, which are useful chemical building blocks. Strategies that prevent over

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• could not be avoided. However, we were interested in expanding the aforementioned structure–activity studies regarding the substitution of the indole moiety by different aromatic systems as well as substitution of side chains in the α-keto carboxylic acids to generate more derivatives of this

• )ethylamine (for 7), respectively. Compounds 8–12 were synthesized by coupling tryptamine with different α-keto carboxylic acids, including 3-furylglyoxylic acid (for 8), 3-indoleglyoxylic acid (for 9), phenylglyoxylic acid (for 10), and isomeric 3-methylpent-2-enoic acid (for 11 and 12) [22], respectively

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• thanks to their tolerance against various functional groups such as amides, alcohols and carboxylic acids. However, one major hurdle for olefin metathesis in chemical biology remains the necessity to perform catalysis under mild conditions in buffered aqueous media. The aqueous ROMP introduced by Grubbs

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• ]. Alkylidene(aminocyclopropane) derivatives constitute another interesting class of heterosubstituted alkylidenecyclopropanes which have been previously synthesized by a Curtius rearrangement of acyl azides derived from alkylidenecyclopropane carboxylic acids [43] or by elimination reactions applied to

• ketene acetals of (Z)-configuration 57a–l, arising from O-silylation of the corresponding chelated potassium enolates [60], underwent an efficient [3,3]-sigmatropic rearrangement upon warming to room temperature. After an acidic work-up and treatment of the crude carboxylic acids with

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• mild conditions, hydrogenolysis of the benzyl ester group to the carboxylic acid and hydrogenation of the C=C double bonds at the silicon atoms (Scheme 7). The ability of the obtained derivatives, in particular the carboxylic acids, to generate nanostructured materials through self-organization

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• scope and relatively low reaction efficiency. Very recently, Fuk Yee Kwong and co-workers (Scheme 1d) developed a straightforward one pot π-extension method using norbornadiene instead of norbornene as directing group to afford the phenanthrenes [11]. However, ortho-haloaryl carboxylic acids employed in

A convenient and practical synthesis of β-diketones bearing linear perfluorinated alkyl groups and a 2-thienyl moiety

• Ilya V. Taydakov,
• Yuliya M. Kreshchenova and
• Ekaterina P. Dolotova

Beilstein J. Org. Chem. 2018, 14, 3106–3111, doi:10.3762/bjoc.14.290

• alkoxides (predominantly NaOMe or NaOEt) and Et2O were used most frequently as the base and solvent, respectively, in the Claisen condensation of 2-acetylthiophene (1) with various esters of aliphatic, aromatic or heterocyclic carboxylic acids [24] (Table 1). In our initial experiments we tested several

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

• stilbene formation. Replacing styrenes by (Z)-β-methylstyrenes (e.g., 32) allowed for successful reactions with methyl ester 33 (Scheme 6a). Hoveyda noted that carboxylic acids (e.g., 34) are not suitable cross-metathesis partners for (Z)-β-methylstyrenes. Hoveyda reasoned that with the sluggishly reacting

Copper(I)-catalyzed tandem reaction: synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and alkynes

• Muhammad Israr,
• Changqing Ye,
• Munira Taj Muhammad,
• Yajun Li and
• Hongli Bao

Beilstein J. Org. Chem. 2018, 14, 2916–2922, doi:10.3762/bjoc.14.270

• from alkyl diacyl peroxides, azidotrimethylsilane, and terminal alkynes is reported. The alkyl carboxylic acids is for the first time being used as the alkyl azide precursors in the form of alkyl diacyl peroxides. This method avoids the necessity to handle organic azides, as they are generated in situ

• functionality of organic azide source. Moreover, as one of the most commonly appearing compounds in nature, carboxylic acids have rarely been directly used as the organic azide precursors for CuAAC reactions, considering the frequent involvement of organic halides. Thus, new methods with non or less toxic

• reagents and enriched organic azide sources for CuAAC reaction are still highly required. Herein, we report a novel CuAAC reaction, using aliphatic carboxylic acids as the alkyl source [36], and TMSN3 as the azide source (Scheme 1b). Because TMSN3 can react with alkynes to form the CuAAC reaction product

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• product solution in chloroform [39]. 1,3-Disulfo-1H-imidazolium carboxylate ILs [Dsim][carboxylate] 17–19 were synthesized using environmentally benign reactions between 1,3-disulfo-1H-imidazolium chloride [Dsim][Cl] (10) and three different carboxylic acids (CH3COOH, CCl3COOH, CF3COOH). The more acidic

• well. The catalytic system worked for nine runs without considerable loss in its activity [45]. In 2017, the synthesis of N,N-disulfo-1,1,3,3-tetramethylguanidinium carboxylate ILs 47a–c through reactions between N,N-disulfotetramethylguanidinium chloride (46) with three carboxylic acids (AcOH

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

• photocatalyst, Cu(tmp)(BINAP)BF4, was found to be active in a photoredox Appel-type conversion of alcohols to bromides. The catalyst was identified from a screening of 50 complexes and promoted the transformation of primary and secondary alcohols to their corresponding bromides and carboxylic acids to their

• -methoxybenzoic acid was isolated in 90% yield. Conclusion In summary, a heteroleptic copper-based photocatalyst Cu(tmp)(BINAP)BF4 was discovered for the photochemical Appel-type conversion of alcohols to bromides, as well as carboxylic acids to their anhydrides. The protocol was highly efficient and could be

Carbonylonium ions: the onium ions of the carbonyl group

• Daniel Blanco-Ania and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2018, 14, 2568–2571, doi:10.3762/bjoc.14.233

• carboxylic acids (carboxylic acidium ions), protonated esters and protonated aldehydes and ketones amongst others [31]. The name thought to be originated from the combination of the terms “carbenium” and “oxonium”, but not correctly applied to such a broad scope of intermediates. Clearly the intermediates

• formed from protonation of carboxylic acids and esters are different than the ones from aldehydes and ketones and therefore should not have the same name. We recommend applying “carboxonium ion” only to intermediates whose carbon atom presents the same oxidation state as carboxylic acids, that is

• , protonated carboxylic acids and esters (6; Figure 2), in agreement with other terms like “carboxy”, “carboxylic”, “carboxylate” and “carboxamide”. To augment confusion, other researchers have used this term to describe “oxycarbenium ions” 2 [32][33]. Carbonylonium ions: aldehydium and ketonium ions We