Hypervalent iodine-mediated Ritter-type amidation of terminal alkenes: The synthesis of isoxazoline and pyrazoline cores

• Sang Won Park,
• Soong-Hyun Kim,
• Jaeyoung Song,
• Ga Young Park,
• Darong Kim,
• Tae-Gyu Nam and
• Ki Bum Hong

Beilstein J. Org. Chem. 2018, 14, 1028–1033, doi:10.3762/bjoc.14.89

• alkene functionalization utilizing a PhI(OAc)2 ((diacetoxyiodo)benzene, PIDA)/Lewis acid combination in order to access isoxazoline and pyrazoline cores. Based on allyl ketone oximes and allyl ketone tosylhydrazones, we have developed an alkene oxyamidation and amido-amidation protocol en route to

• . Keywords: amido-amidation; hypervalent iodine; isoxazoline; metal-free; oxyamidation; pyrazoline; Introduction Isoxazoline and pyrazoline-containing heterocycles are abundant in natural products and biologically active molecules [1][2][3][4][5]. Thus, these scaffolds are also important from the standpoint

• (see Supporting Information File 1, Table S1). Upon optimization with various oxidants and additives screened, it was found that a Lewis acid additive can promote the olefin heterofunctionalization via a Ritter-type amidation using acetonitrile as both the solvent and the amine source. Interestingly

Preparation, structure, and reactivity of bicyclic benziodazole: a new hypervalent iodine heterocycle

• Akira Yoshimura,
• Michael T. Shea,
• Cody L. Makitalo,
• Melissa E. Jarvi,
• Gregory T. Rohde,
• Akio Saito,
• Mekhman S. Yusubov and
• Viktor V. Zhdankin

Beilstein J. Org. Chem. 2018, 14, 1016–1020, doi:10.3762/bjoc.14.87

• ), which is in agreement with the previously proposed mechanism of oxidatively assisted esterification or amidation [23][38]. Conclusion In summary, we have prepared the new bicyclic benziodazole 7a by the oxidation of 2-iodo-N,N’-diisopropylisophthalamide (6a) with m-CPBA. The solid structure of 7a was

• (1)–N(1) 2.177 (4) Å; N(1)–I(1)–C(1) 76.89 (18)°; N(2)–I(1)–C(1) 77.02 (18)°; N(1)–I(1)–N(2) 153.90 (15)°. Representative examples of benziodoxoles and benziodazoles. Preparation of bicyclic benziodazole 7a. Benziodadiazole 7a mediated oxidatively assisted esterification and amidation reactions

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• reasonable mechanism for the formation of 3,4-diamide groups, besides the amidation of ethyl ester group on the 2-position to give one amide group on the pyrrole ring. Due to the electron-withdrawing effect of the ester group at the 2-position in 12a–k, the carbonyl group at the 3-position of the pyrrole was

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• functionalized carbohydrates (Figure 1c). Various types of reaction, such as reductive amination [32], oxime formation [33], amidation [34], and perfluorophenyl azide (PFPA) photocoupling [35][36], have been used to functionalize the surface of AuNPs with carbohydrates. The detailed information regarding the

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• traditional Pd-catalyzed aryl–heteroaryl coupling to biaryls [57]. Since then, KOt-Bu has been used as a mediator for various reactions including aryl–aryl coupling [58][59][60][61][62][63], inter- and intramolecular cyclizations [64][65][66][67][68], amidation [69], alkenylation [70], oxidation [71] and

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• acid 74, which was then used in a double amidation with cystamine to give the target compound 72 after unmasking of oxime. A series of other psammaplin A analogs were prepared in a similar manner. Reduction of the oxime group in oximinoalkylated indoles provides a direct access to various substituted

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• the metal catalyst from rhodium to iridium. In 2016, using an Ir(III) catalyst an unprecedented ortho-selective Csp2–H bond amidation of benzamides with sulfonyl azides as the amide source was done under solvent-free ball mill conditions (Scheme 51) [183]. They could also isolate cyclic iridium

• in good to excellent yield within 1 h. Dimethyl formamide (DMF) acted as ligand during the activation process (Scheme 53). The protocol was also equally applicable to electron deficient oximes and electron rich anilides [185]. Bolm and co-workers reported a Rh-catalyzed amidation of Csp2–H bonds

• using dioxazolone as the amide source under ball milling conditions (Scheme 54). Using 5 mol % of Rh catalyst, 20 mol % of AgSbF6 and 20 mol % of AgOAc they have successfully achieved up to 99% of ortho-amidation product with diversely substituted arene moiety [186]. Recently Bolm and co-workers

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• conditions studied. With the optimal cyclization conditions in hand, the scope of this cyclization process was investigated for a range of propargylamides 4 which are readily accessible from propargylamine by amidation and Sonogoshira coupling (Scheme 2) [39]. The cyclization was successful in all cases

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• corresponding diethyl amide 12. For this purpose, ester 10c was reacted in a Weinreb amidation [32] with a mixture of trimethylaluminium and diethylamine to give the amide 12 in 31% yield (Scheme 5). The diethyl amide moiety was designated to promote a directed remote metalation by lithium diisopropylamide (LDA

• methyl 2-bromo-5-methoxybenzoate (14) in 68% yield. Methyl ester 15 was converted into the corresponding diethyl amide 16 in 58% yield by Weinreb amidation following the protocol described above for the synthesis of 12 (Scheme 7). Incubation of methyl ester 15 with LDA (4 equiv LDA, 25 °C) over a period

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• employed for this purpose (i.e., click reaction, amidation, conjugation via carbonyldiimidazol and perfluorophenyl azide (PFPA) photo-coupling) have to be compatible with water, the common medium for AuNP preparation [25][26][27][28][29]. One example of the three-step approach was described by Tian and co

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• facilitate C–H hydroxylation of benzoic acids and heteroarenes [55]. An amidation reaction between benzoic acid and 2-(pyridine-2-yl)isopropylamine gave N-(2-(pyridine-2-yl)isopropyl)benzamides, which could be hydroxylated at the ortho position in moderate to excellent yields. The reaction was promoted by a

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• challenge in the syntheses of glorin and analogs is the differentiation between the α- and the γ-carboxylic acid groups of L-glutamic acid for selective esterification or amidation. α-Selective functionalization was achieved via synthesis of oxazolidinone 6 from Cbz-L-glutamic acid (5) with paraformaldehyde

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• methyl 10-undecenoate which was subjected to a thiol–ene reaction with cysteamine hydrochloride. Further amidation of the amine was carried out with different phenolic acids such as caffeic, ferulic, sinapic, coumaric and cinnamic acid. All synthesized compounds were fully characterized and their

• via amidation. The evaluation of the five novel phenolic lipids as anti-oxidants was studied using the DPPH radical scavenging assay and DSC studies where some compounds showed excellent anti-oxidant activity. Finally the compounds were further screened for anticancer activity where a few derivatives

• product was characterized by 1H and 13C NMR, IR and ESIMS spectral studies and the structure was confirmed by comparing the data with those reported in the literature [15]. Synthesis of methyl 11-((2-(cinnamamido)ethyl)sulfanyl)undecanoate (3a): The amidation reaction was performed following a reported

Electron-transfer-initiated benzoin- and Stetter-like reactions in packed-bed reactors for process intensification

• Anna Zaghi,
• Daniele Ragno,
• Graziano Di Carmine,
• Carmela De Risi,
• Olga Bortolini,
• Pier Paolo Giovannini,
• Giancarlo Fantin and
• Alessandro Massi

Beilstein J. Org. Chem. 2016, 12, 2719–2730, doi:10.3762/bjoc.12.268

• homogeneous conditions and their subsequent utilization in transesterification and amidation processes by the reaction telescoping approach [12]. Similarly, the group of Brown reported on the oxidative esterification and amidation of aldehydes in undivided microfluidic electrolysis cells mediated by

Methylenelactide: vinyl polymerization and spatial reactivity effects

• Judita Britner and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 2378–2389, doi:10.3762/bjoc.12.232

• quantitative amidation reactions with aliphatic primary amines under mild conditions [7]. In the underlying study, we focused on spatial effects with respect to interactions between neighboring lactide rings. Based on these findings, polymer analogous reactions of poly(MLA) with different alcohols were

TBHP-mediated highly efficient dehydrogenative cross-oxidative coupling of methylarenes with acetanilides

• Cui Chen,
• Weibing Liu and
• Peng Zhou

Beilstein J. Org. Chem. 2016, 12, 2250–2255, doi:10.3762/bjoc.12.217

• ]. What is more, the amide motif has also served as pivotal intermediate to generate several other organic functionalities [8][9]. To date, a large number of amidation reactions have been established [10][11], such as the condensation of carboxylic acid derivatives with amines [12], the rearrangement of

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• the ethyl ester of 11 was determined NMR spectroscopically including nOe experiments (see Supporting Information File 1). Next, vinyl iodide 10 was subjected to amidation with L-alanine methylate (resembling position 2 in myxovalargin) using the reagent system PyAOP, HOAt, DIPEA to yield amide 12

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• copper catalysis is in the C–N bond formation by using carbon sources and nitrogen functional groups such as amides. In this review, the recent progress in the amidation reactions employing copper-catalyzed C–H amidation is summarized. Keywords: amidation; C–H bond; cascade reactions; Copper catalysis

• , pharmaceutical, biological and material sciences [1][2][3][4][5]. For the sake of synthesizing functional amides, tremendous efforts have been made by chemists who developed many distinct methodologies towards these compounds. Typical examples on amide synthesis are the direct amidation of acids/esters/acyl

• chloride/anhydrides [6][7][8][9][10][11], nitrile hydrolysis [12][13][14][15][16], Goldberg C–N cross coupling reaction [17], aldehyde/ketone amidation [18][19][20][21][22][23], the transamidation [24][25][26][27][28][29], and oxime rearrangement [30][31][32][33], to name only a few. It is obvious that the

Molecular-oxygen-promoted Cu-catalyzed oxidative direct amidation of nonactivated carboxylic acids with azoles

• Wen Ding,
• Shaoyu Mai and
• Qiuling Song

Beilstein J. Org. Chem. 2015, 11, 2158–2165, doi:10.3762/bjoc.11.233

• scope. The mechanistic studies reveal that oxygen plays an essential role in the success of the amidation reactions with copper peroxycarboxylate as the key intermediate. Transamidation occurs smoothly between azole amide and a variety of amines. Keywords: amidation; azoles; Cu-catalyzed; molecular

• amidation reaction from carboxylic acids with peroxycarboxylate as the key intermediate, which represents a novel activation mode with molecular oxygen as the activating reagent. Most remarkably, in sharp contrast to previous reports (which used complex N-containing ligands to form copper superoxide

• ), inexpensive and readily available pyridine was employed as both the ligand and base in our case. Results and Discussion Our initial exploration commenced with benzoic acid (1) and benzimidazole (2) as the model substrates to investigate the copper-catalyzed oxidative direct amidation reaction (Table 1). The

Intermolecular addition reactions of N-alkyl-N-chlorosulfonamides to unsaturated compounds

• Gerold Heuger and
• Richard Göttlich

Beilstein J. Org. Chem. 2015, 11, 1226–1234, doi:10.3762/bjoc.11.136

• and polar pathways as competing mechanisms and has developed a nice copper-catalyzed oxidative amidation of alkenes whilst Muñiz [27] in a recent publication proposes a polar sulfonamido-chlorination mechanism of alkenes. Similar, intramolecular and intermolecular additions of N-chlorosulfonamides and

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• several research groups reported on specific flow transformations that enabled a new synthesis of these known pharmaceuticals. Examples of these early endeavours include the syntheses of efaproxiral (1) and rimonabant (2) using a AlMe3-mediated direct amidation in flow [40], an improved metalation step in

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• amidation of aryl halides [51][52]. Examples of TTF derivatives synthesised using this protocol by other groups include: MPTTF and BPTTF-triarylamine conjugates (as possible charge-transport materials) [53], MPTTF-triarylborane conjugates (with possible applications as fluoride sensors) [54], and MPTTF

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• alkyne by oxidative amidation using carbon tetrachloride with propargylamine. The microwave-assisted click-conjugation was performed on a solid phase upon completion of the DNA synthesis (Scheme 4). Lönnberg and co-workers prepared a thymidine modified at the 4’-position with an azidomethyl group to

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• compounds to form C–C, C–N, C–O, C–Hal, C–P, and N–N bonds [10], the Bu4NI/t-BuOOH oxidative system [22], selective functionalization of molecules [23], the oxidative esterification and oxidative amidation of aldehydes [24], and the transition metal-catalyzed radical oxidative cross-couplings [13]. The

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• the peptide segment (Phe-Arg-Gly-Asp or naphthAla-Phe-Arg-Gly-Asp with fully protected groups), and later, an amidation reaction in liquid phase connects these three parts together. The overall yield of these multiple step synthesis is about 34%. Besides exhibiting excellent solubility, these

• (DIC)-catalyzed amidation reaction. As demonstrated by the example of the synthesis of 3, the use of reported methods [31][32][33][34][35] (Scheme 1) affords the nucleobase and saccharide derivatives 12, 16, and 19. We used SPPS [36] (Scheme 2) to synthesize the fully protected naphthAla-Phe-Arg-Gly