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

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• catalyst in acetonitrile, and a high pressure of both, CO and air, are needed in order to perform an oxidative carbonylation on 2-ethynylbenzamide 21. Up to ten compounds were obtained with yields ranging from 65 to 96%. Butyl, phenyl, benzyl or absence of substitution on the amide nitrogen produced, in

• transformation implies initial formation of an alkynylpalladium intermediate 25 followed by carbonylation to render acylpalladium 26 (Scheme 6). Reductive substitution of palladium by amine 22 furnishes diamide derivative 27 and Pd(0), which is reoxidized to Pd(II) again by HI and oxygen. Then, intramolecular

• -catalysed carbonylation of iodoarylimine 100 to produce acid chloride 102 (Scheme 29). Intramolecular nucleophilic attack of the imine onto the acyl chloride would furnish cyclic N-acyliminium derivative 103, which can then undergo a second palladium-catalysed carbonylation to form a stabilized ketene 104

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• alkylidenecyclopropanes 1 with allylic bromides 78 for the synthesis of 2-bromo-1,6-dienes 79 via radical ring-opening and SH2’ reactions (path V in Scheme 17) [95]. The experimental results suggested that radical carbonylation could also be incorporated in the reaction sequence, leading to 2-bromo-1,7-dien-5-ones 80

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• activation. In 1941, Kharasch and Fields applied a cobalt salt as the catalyst for the homocoupling of Grignard reagents [28]. After 15 years, Murahashi discovered a cobalt-catalyzed chelation-assisted ortho C–H carbonylation of azobenzene and imines as the preliminary example of directing group assisted C–H

• C–H carbonylation. Hydroarylation by C–H activation. Pathways for cobalt-catalyzed hydroarylations. Co-catalyzed hydroarylation of alkynes with azobenzenes. Co-catalyzed hydroarylation of alkynes with 2-arylpyridines. Co-catalyzed addition of azoles to alkynes. Co-catalyzed addition of indoles to

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• ]. Oxyarylation of alkenes [71]. Asymmetric oxidative rearrangements of alkenes [72]. Bromolactonization of alkenes [75]. Bromination of alkenes [77][78]. Cooperative strategy for the carbonylation of alkenes [79]. Acknowledgements We are grateful for financial support from the National Nature Science Foundation

Synthesis and stability of strongly acidic benzamide derivatives

• Frederik Diness,
• Niels J. Bjerrum and
• Mikael Begtrup

Beilstein J. Org. Chem. 2018, 14, 523–530, doi:10.3762/bjoc.14.38

• ][32][33]. Finally, two examples of syntheses via palladium-catalyzed carbonylation of trifluoromethanesulfonamide (1) have been reported [34][35]. The N-triflylbenzamides have only been explored as substrates in a few reactions. A recent report describes using N-triflylbenzamide as a directing group

Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes

• Hao Wang,
• Cui Chen,
• Weibing Liu and
• Zhibo Zhu

Beilstein J. Org. Chem. 2017, 13, 2023–2027, doi:10.3762/bjoc.13.200

• dioxygenation [10][11], dihydroxylation [10][12], bisperoxidation [13], oxyamidation [14], aminohydroxylation [15], oxyphosphorylation [16], deamination [17] and carbonylation–peroxidation [18]. Several very recent reports have pertained to metal-free catalysts for difunctionalization of alkenes such as UV

Ionic liquids as transesterification catalysts: applications for the synthesis of linear and cyclic organic carbonates

• Maurizio Selva,
• Alvise Perosa,
• Sandro Guidi and
• Lisa Cattelan

Beilstein J. Org. Chem. 2016, 12, 1911–1924, doi:10.3762/bjoc.12.181

• by Ube Industries [59]. The EniChem process involved an oxidative carbonylation of methanol, i.e., the reaction of methanol with carbon monoxide and oxygen catalyzed by cuprous chloride, while the Ube process used an oxidative carbonylation of methanol via methyl nitrite using NOx as oxidant, instead

Flow carbonylation of sterically hindered ortho-substituted iodoarenes

• Carl J. Mallia,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1503–1511, doi:10.3762/bjoc.12.147

• via a reverse “tube-in-tube” flow reactor at elevated pressures to give yields of carboxylated products that are much higher than those obtained under normal batch conditions. Keywords: carbon monoxide; carbonylation of ortho-substituted substrates; flow chemistry; gases in flow; “tube-in-tube

• ”; Introduction Carbonylation reactions have received a great deal of attention both in batch as well as in flow (using plug/annular flow reactors [1][2][3][4][5] or “tube-in-tube” reactors [6][7][8][9][10]) and generally produce the desired products in good yields [11][12][13][14]. This is not the case though

• for the carbonylation of ortho-substituted substrates which are much more challenging as highlighted by the limited literature precedence [15][16][17]. However, these products are of considerable industrial importance, especially the amide and ester derivatives, which are commonly found in

Synthesis of 2-substituted tetraphenylenes via transition-metal-catalyzed derivatization of tetraphenylene

• Shulei Pan,
• Hang Jiang,
• Yanghui Zhang,
• Yu Zhang and
• Dushen Chen

Beilstein J. Org. Chem. 2016, 12, 1302–1308, doi:10.3762/bjoc.12.122

• research on the properties and application of tetraphenylene derivatives. Keywords: acetoxylation; carbonylation; halogenation; tetraphenylene; transition metal; Introduction Tetraphenylene (1) is one of the simplest motifs in the eight-membered ring aromatic compounds (Figure 1) [1][2]. Based on its

• ). Having successfully developed protocols for introducing OAc and X (Cl, Br, I) onto tetraphenylene (1), we next turned to investigate the carbonylation of tetraphenylene (1). The carbonyl group is a common structural element present in both natural products and functional materials and can be transformed

• into other functionalities [58][59]. The Larock group reported a novel Pd-catalyzed addition of nitriles to an arene C–H bond for the synthesis of aryl ketones [60][61]. Following the Larock’s conditions, we investigated the carbonylation of tetraphenylene (1) and the carbonylated product 5a was

Opportunities and challenges for direct C–H functionalization of piperazines

• Zhishi Ye,
• Kristen E. Gettys and
• Mingji Dai

Beilstein J. Org. Chem. 2016, 12, 702–715, doi:10.3762/bjoc.12.70

• six-membered ring [51]. As of yet only a few examples have been reported so far and are far from being general and practical; no enantioselective versions have been shown. Rhodium-catalyzed dehydrogenative carbonylation In 1997, Murai and co-workers reported a novel Rh-catalyzed α-C–H

• -functionalization reaction of N-(2-pyridinyl)piperazines with carbon monoxide and terminal olefins (Figure 13) [52]. Their previous work on pyridinyl group-directed Rh-catalyzed carbonylation at sp3 C–H bonds adjacent to the nitrogen atom in other alkylamines such as pyrrolidine, piperidine, and

• tetrahydroisoquinoline [53][54] gave the carbonylation product directly. However, when piperazine substrates were used, an additional formal dehydrogenation process took place before the carbonylation reaction. As shown in Figure 13, under the conditions of 15 atm of carbon monoxide and ethylene, Rh4(CO)12 catalyst, and

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• catalysed carbonylation reactions using the meta- and para-iodo derivatives of all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane (4) are illustrated as the start point for a variety of functional group interconversions. The resultant benzaldehyde and benzoic acids offer novel building blocks for further

• derivatisation and facilitate the incorporation of the facially polarised all-cis-1,2,4,5-tetrafluorocyclohexane motif into more advanced molecular scaffolds. Keywords: cyclohexane carbonylation; fluorine containing building blocks: organofluorine chemistry; Introduction Selectively fluorinated building blocks

• ]. In this paper it is demonstrated that palladium mediated carbonylation of the aryl iodinated derivatives 5–7 forms the basis of a diversity of new products which may prove attractive as building blocks for structure activity studies in bioactive research projects. Results and Discussion A key

One-pot synthesis of cyanohydrin derivatives from alkyl bromides via incorporation of two one-carbon components by consecutive radical/ionic reactions

• Shuhei Sumino,
• Akira Fusano,
• Hiroyuki Okai,
• Takahide Fukuyama and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2014, 10, 150–154, doi:10.3762/bjoc.10.12

• bromides and nucleophilic addition of a cyanide ion was investigated, which gave moderate to good yields of cyanohydrin derivatives in one-pot. Keywords: alkyl bromide; carbon monoxide; cyanohydrin; ethyl cyanoformate; multicomponent; radical reaction; Introduction Radical carbonylation reactions have

• , AIBN, and Et3N, which gave moderate to good yields of cyanohydrin derivatives 3. This protocol represents a one-pot method [32][33] based on radical carbonylation and ionic cyanation. Experimental Typical procedure for radical/ionic three-component coupling reaction leading to cyanohydrin derivatives 1

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• Diego Carnaroglio,
• Katia Martina,
• Giovanni Palmisano,
• Andrea Penoni,
• Claudia Domini and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2013, 9, 2378–2386, doi:10.3762/bjoc.9.274

• molecular weight compounds impossible. Apart from the catalytic carbonylation of nitro compounds, which is one of the most interesting alternatives for the synthesis of aromatic isocyanates, other alternative greener, non-phosgene routes to isocyanates have also been developed [9]. Of these, the Curtius

Flow Giese reaction using cyanoborohydride as a radical mediator

• Takahide Fukuyama,
• Takuji Kawamoto,
• Mikako Kobayashi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2013, 9, 1791–1796, doi:10.3762/bjoc.9.208

• C–C bond forming reactions or radical reduction as efficient substitutes for tin hydride reagents, whose toxicity is of great concern to organic chemists. Thus far we have demonstrated the borohydride-based tin-free Giese reactions [10] and the related radical carbonylation and hydroxymethylation

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• -lactams in which CO was introduced as the lactam carbonyl moiety [17][18][19][20][21][22][23]. Our approach consists of a sequence of aryl radical cyclization, radical carbonylation [24][25][26][27], and spirocyclization of the resulting acyl radical onto an azide group, which can give 4,4-spirocyclic γ

• chemistry of radical cyclization and carbonylation reactions, a possible mechanism for the spirocyclization of 1f with CO is shown in Scheme 5. The iodoaryl allyl azide 1f is converted to an aryl radical A via the iodine atom abstraction by the (TMS)3Si radical. The subsequent 5-exo cyclization of aryl

• next chain reaction. Conclusion We have examined a TTMSS-mediated 5-exo radical cyclization/carbonylation/spirocyclization sequence to synthesize 4,4-spirocyclic rings. By using this protocol, indoline, benzofuran and oxindole γ-lactams can be conveniently prepared in moderate to good yields. As shown

Synthesis of conformationally restricted glutamate and glutamine derivatives from carbonylation of orthopalladated phenylglycine derivatives

• Esteban P. Urriolabeitia,
• Eduardo Laga and
• Carlos Cativiela

Beilstein J. Org. Chem. 2012, 8, 1569–1575, doi:10.3762/bjoc.8.179

• results, however, in the formation of the cyclic isoindolinone or the open 2-carboxyphenylglycine methyl esters, with the reaction outcome being driven by the choice of the solvent. Keywords: C–H functionalization; carbonylation; glutamic acid; glutamide; palladium; phenylglycine; Introduction The

• phenyl ring, and the corresponding synthesis of a new family of orthopalladated complexes [12]. The carbonylation of these compounds allows for a general synthesis of methyl (1H)-isoindolin-1-one-3-carboxylates under very mild reaction conditions, regardless of whether the substituents at the aryl ring

• reactivity found for 1, and shown in Scheme 3, when compared to related Pd complexes previously reported by us [12], resumed in Scheme 1. Therefore, the synthesis of the methyl (1H)-isoindolin-1-one-3-carboxylates by carbonylation of [Pd(μ-Cl)(C6H4CH(CO2Me)NH2-2)]2 occurs by C–N coupling, irrespective of the

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• synthesis of isoindolones and phthalazones starting from ortho-halogenated cinnamates 34 and related compounds in the presence of hydrazine derivatives and carbon monoxide. The process is thought to begin with carbonylation of the starting aryl iodide to give an acylpalladium species 35, which is

• developed several multicomponent approaches for the synthesis of nitrogen-containing heterocycles based on a palladium-mediated carbonylation reaction [44]. An interesting, related strategy for the preparation of unsaturated seven-membered ring lactams 84, starting from a Baylis–Hillman adduct bearing an

• . Synthesis of indoles through a sequential C–C coupling/desilylation–coupling/cyclization reaction. Synthesis of indoles by a site selective Pd/C catalyzed cross-coupling approach. Synthesis of isoindolin-1-one derivatives through a sequential Sonogashira coupling/carbonylation/hydroamination reaction

Koch–Haaf reaction of adamantanols in an acid-tolerant hastelloy-made microreactor

• Takahide Fukuyama,
• Yu Mukai and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2011, 7, 1288–1293, doi:10.3762/bjoc.7.149

• practical organic syntheses using flow microreactors, and we have reported thus far examples of Pd-catalyzed coupling reactions [11][12][13], radical reactions [14][15][16], and photoreactions [17][18][19][20][21]. Carbonylation reactions are a powerful tool for the introduction of carbon monoxide into

• organic molecules, and we also reported that Pd-catalyzed carbonylation [13] and radical carbonylation [16] could be successfully carried out in a continuous microflow system with higher efficiency than in a batch autoclave system. In this study, we focused on the carbonylation of carbocation

• intermediates carried out in a continuous microflow system [22][23][24]. The Koch–Haaf reaction [25], that is the carbonylation of alcohols or olefins with formic acid in the presence of a strong acid, is an important reaction for the preparation of carboxylic acids, which are widely used in organic synthesis

Molecular rearrangements of superelectrophiles

• Douglas A. Klumpp

Beilstein J. Org. Chem. 2011, 7, 346–363, doi:10.3762/bjoc.7.45

• gives the cyclopentenone derivative 63. Carbonylation of superelectrophiles has been shown to give acids and esters in good yields [26]. A rearrangement was described in the carbonylations of dialkyl ketones in HF-SbF5 (Scheme 14). Thus, ketone 64 reacts at 20 °C to give 65–67 as products of

• carbonylation. At this temperature, the rearrangement product 67 is the major product, whilst at −20 °C compound 65 is the major product. The formation of these products can be understood to be the result of two reactions with the superacid: Protonation of the carbonyl group and protolysis of C–H σ-bonds. As a

Radical carbonylations using a continuous microflow system

• Takahide Fukuyama,
• Md. Taifur Rahman,
• Naoya Kamata and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2009, 5, No. 34, doi:10.3762/bjoc.5.34

• Takahide Fukuyama Md. Taifur Rahman Naoya Kamata Ilhyong Ryu Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan 10.3762/bjoc.5.34 Abstract Radical-based carbonylation reactions of alkyl halides were conducted in a microflow reactor under

• carbonylation; radical mediator; V-65; Introduction Placing a reaction mixture fluid inside a microstructured channel network helps gain a high surface area to volume ratio that in turn ensures rapid heat and mass transfer [1][2][3]. Precise control of reaction temperature and residence time, excellent mixing

• yields of the desired products. Carbon monoxide is an important feedstock and our group has actively pursued carbonylation reactions [14][15][16][17]. Thermally induced radical carbonylations using tin hydride usually require pressurized CO conditions to ensure that the concentration of CO around the

Synthesis of novel photochromic pyrans via palladium- mediated reactions

• Christoph Böttcher,
• Gehad Zeyat,
• Saleh A. Ahmed,
• Elisabeth Irran,
• Thorben Cordes,
• Cord Elsner,
• Wolfgang Zinth and
• Karola Rueck-Braun

Beilstein J. Org. Chem. 2009, 5, No. 25, doi:10.3762/bjoc.5.25

• cyanation, carbonylation and Sonogashira cross-coupling starting from bromo-substituted naphthopyran 1 and benzopyrans 2a/b. A novel photoswitchable benzopyran-based ω-amino acid 6 for Fmoc-based solid-phase peptide synthesis is presented. The photochromic behaviour of the 3-cyano-substituted benzopyran 5a

• rearrangement reactions [25]. Since nitriles are important intermediates in the synthesis of carboxylic acids and derivatives, and for the introduction of aminomethyl substituents, we started our studies with palladium-catalyzed cyanation reactions. The studies were then extended towards a Heck carbonylation in

• in good to excellent yields (Scheme 6). Starting from the bromo-substituted pyran 2b a final carbonylation step (Scheme 6) would directly complete the synthesis of an Fmoc-protected ω-amino acid. Though many protocols for Heck carbonylations are known, only a few report neutral reaction conditions

Recent progress on the total synthesis of acetogenins from Annonaceae

• Nianguang Li,
• Zhihao Shi,
• Yuping Tang,
• Jianwei Chen and
• Xiang Li

Beilstein J. Org. Chem. 2008, 4, No. 48, doi:10.3762/bjoc.4.48

• double Sharpless AE/Sharpless AD. The building block 157 was then constructed through bidirectional chain synthesis strategy. The propargylic alcohol 159, obtained from 1,4-bis(alkenyloxy)benzene 158, was converted into butenolide 160 through Red-Al reduction, iodine treatment, and carbonylation

Development of potential manufacturing routes for substituted thiophenes – Preparation of halogenated 2-thiophenecarboxylic acid derivatives as building blocks for a new family of 2,6-dihaloaryl 1,2,4-triazole insecticides

• John W. Hull Jr.,
• Duane R. Romer,
• David E. Podhorez,
• Mezzie L. Ash and
• Christine H. Brady

Beilstein J. Org. Chem. 2007, 3, No. 23, doi:10.1186/1860-5397-3-23

• /debromination procedure developed for 3-methylthiophene gave 2,4-dibromo-3-methylthiophene. Carboxylic acid functionality was then introduced either by a Grignard metallation followed by carbonation with CO2, or by a palladium catalyzed carbonylation procedure under CO pressure. The vapor phase chlorination of

• -catalyzed carbonylation under CO pressure in EtOH gave ester 12b. Unlike 5, the esters 12 could be subjected to a one-pot bromination/debromination sequence with Br2 in acetic acid, followed by Zn dust treatment, to give the 4-bromoester 13, which was readily hydrolyzed to the acid 19. This resulted in a

• catalyzed carbonylation procedure [17][18] under CO pressure in Et3N/water using the chelating diphosphine ligand 1,3-bis (diphenylphosphino)propane (DPPP), [19][20] (Scheme 2). The palladium catalyzed carbonylation procedure was also used to prepare esters 12 from 11. This procedure, [17] which used