- HEXACARBONYLMOLYBDENUM- OR NONACARBONYLDIIRON-INDUCED REACTION OF 1,3-OXAZEPINE RING SYSTEM. EVIDENCE FOR THE VALENCE ISOMERIZATION BETWEEN 1,3-OXAZEPINE AND PYRIDINE-2,3-OXIDE
-
Upon treatment with or , phenyl-substituted 1,3-oxazepines undergo the C-2-O and C-7-O bond cleavage to give pyridine and pyrrole derivatives via a coordinated pyridine-2,3-oxide.
- Nitta, Makoto,Kobayashi, Tomoshige
-
-
Read Online
- Increase of Direct C-C Coupling Reaction Yield by Identifying Structural and Electronic Properties of High-Spin Iron Tetra-azamacrocyclic Complexes
-
Macrocyclic ligands have been explored extensively as scaffolds for transition metal catalysts for oxygen and hydrogen atom transfer reactions. C-C reactions facilitated using earth abundant metals bound to macrocyclic ligands have not been well-understood but could be a green alternative to replacing the current expensive and toxic precious metal systems most commonly used for these processes. Therefore, the yields from direct Suzuki-Miyaura C-C coupling of phenylboronic acid and pyrrole to produce 2-phenylpyrrole facilitated by eight high-spin iron complexes ([Fe3+L1(Cl)2]+, [Fe3+L4(Cl)2]+, [Fe2+L5(Cl)]+, [Fe2+L6(Cl)2], [Fe3+L7(Cl)2]+, [Fe3+L8(Cl)2]+, [Fe2+L9(Cl)]+, and [Fe2+L10(Cl)]+) were compared to identify the effect of structural and electronic properties on catalytic efficiency. Specifically, catalyst complexes were compared to evaluate the effect of five properties on catalyst reaction yields: (1) the coordination requirements of the catalyst, (2) redox half-potential of each complex, (3) topological constraint/rigidity, (4) N atom modification(s) increasing oxidative stability of the complex, and (5) geometric parameters. The need for two labile cis-coordination sites was confirmed based on a 42% decrease in catalytic reaction yield observed when complexes containing pentadentate ligands were used in place of complexes with tetradentate ligands. A strong correlation between iron(III/II) redox potential and catalytic reaction yields was also observed, with [Fe2+L6(Cl)2] providing the highest yield (81%, -405 mV). A Lorentzian fitting of redox potential versus yields predicts that these catalysts can undergo more fine-tuning to further increase yields. Interestingly, the remaining properties explored did not show a direct, strong relationship to catalytic reaction yields. Altogether, these results show that modifications to the ligand scaffold using fundamental concepts of inorganic coordination chemistry can be used to control the catalytic activity of macrocyclic iron complexes by controlling redox chemistry of the iron center. Furthermore, the data provide direction for the design of improved catalysts for this reaction and strategies to understand the impact of a ligand scaffold on catalytic activity of other reactions.
- Brewer, Samantha M.,Wilson, Kevin R.,Jones, Donald G.,Reinheimer, Eric W.,Archibald, Stephen J.,Prior, Timothy J.,Ayala, Megan A.,Foster, Alexandria L.,Hubin, Timothy J.,Green, Kayla N.
-
-
Read Online
- C-vinylation of 1-vinylpyrroles with benzoylacetylene on silica gel
-
1-Vinylpyrroles readily add to benzoylacetylene on grinding the reagents with silica gel at room temperature to form 2-(E)-(2-benzoylvinyl)-1-vinylpyrroles in 50-84% yield in a regioand stereoselective manner.
- Trofimov,Stepanova,Sobenina,Mikhaleva,Ushakov,Elokhina
-
-
Read Online
- A highly efficient and stereoselective cycloaddition of nitrones to N-vinylpyrroles
-
1,3-Dipolar cycloadditions of a number of C-aryl, C-carbamoyl-, and C,C-bis(methoxycarbonyl)nitrones and substituted N-vinylpyrroles proceed with high efficiency and regioselectivity with the formation of only one isomeric substituted 5-(1H-pyrrol-1-yl)isoxazolidine cycloadduct. Georg Thieme Verlag Stuttgart · New York.
- Molchanov, Alexander P.,Savinkov, Ruslan S.,Stepakov, Alexander V.,Starova, Galina L.,Kostikov, Rafael R.,Barnakova, Victoriya S.,Ivanov, Andrey V.
-
-
Read Online
- Mechanistic Insights into Iron-Catalyzed C-H Bond Activation and C-C Coupling
-
Iron-catalyzed C-C coupling reactions of pyrrole provide a unique alternative to the traditional Pd-catalyzed counterpart. However, many details regarding the actual mechanism remain unknown. A series of macrocyclic iron(III) complexes were used to evaluate specifics related to the role of O2, radicals, and μ-oxodiiron-complex participation in the catalytic cycle. It was determined that the mononuclear tetra-Azamacrocyclic complex is a true catalyst and not a stoichiometric reagent, while more than one equivalent of a sacrificial oxidant is needed. Furthermore, the reaction does not proceed through an organic radical pathway. μ-Oxodiiron complexes are not involved in the main catalytic pathway, and the dimers are, in fact, off-cycle species that decrease catalytic efficiency.
- Brewer, Samantha M.,Schwartz, Timothy M.,Mekhail, Magy A.,Turan, Lara S.,Prior, Timothy J.,Hubin, Timothy J.,Janesko, Benjamin G.,Green, Kayla N.
-
-
Read Online
- Intramolecular H-atom abstraction in γ-azido-butyrophenones: Formation of 1,5 ketyl iminyl radicals
-
Photolysis of γ-azidobutyrophenone derivatives yields 1,4 ketyl biradicals via intramolecular H-atom abstraction. The 1,4 ketyl biradicals expel a nitrogen molecule to form 1,5 ketyl iminyl biradicals, which decay by ring closure to form a new carbon-nitr
- Muthukrishnan, Sivaramakrishnan,Sankaranarayanan, Jagadis,Klima, Rodney F.,Pace, Tamara C. S.,Bohne, Cornelia,Gudmundsdottir, Anna D.
-
-
Read Online
- PYRROLES FROM KETOXIMES AND ACETYLENE. 39. EFFECT OF THE NATURE OF THE ALKALI METAL CATION AND THE SOLVENT ON THE REACTION RATE IN MOH-DMSO SYSTEMS
-
The principal tendencies of the effect of the nature of the cation of the hydroxide (Li+, Na+, K+, Rb+, Cs+), and the solvent (DMSO, hexamethylphosphoric triamide (HMPT), 1-methyl-2-pyrrolidone, sulfolane, DMF, polyethylene glycol, hydrazine hydrate, tetramethylurea), and the additive (cesium and rubidium salts and linear macrocyclic polyethers) in the KOH-DMSO catalytic system on the processes involved in the pyrrolization of acetophenone oxime with acetylene and the vinylation of the resulting 2-phenylpyrrole were ascertained.
- Korostova, S. E.,Shevchenko, S. G.,Polubentsev, E. A.,Mikhaleva, A. I.,Trofimov, B. A.
-
-
Read Online
- 2-phenylpyrrole: One-pot selective synthesis from acetophenone oxime and acetylene by a Trofimov reaction
-
We have developed a technologically orientated, one-pot way of synthesis of high purity 2-phenylpyrrole in 74% yield by treatment of acetophenone oxime with acetylene in the KOH-DMSO system. The reaction is carried out at 135-150°C under an acetylene atmospheric pressure. The synthesis was performed in laboratory (glass apparatus) and in a large scale (10 l reaction vessel).
- Mikhaleva,Petrova,Sobenina
-
-
Read Online
- Regioselective C3-Phosphonation of Free Indoles via Transition-Metal-Free Radical/Hydrolysis Cascade
-
The selectivity is of great importance for the preparation of molecules in organic chemistry. Herein, a novel method to enable the highly regioselective C3-phosphonation of free indoles has been developed. This transformation involves a radical and a hydrolysis procedure, and tolerates a range of functional groups, which gives an efficient route toward the 1H-indol-3 – ylphosphonic acid monoesters in one step.
- Guo, Shengmei,Jie, Kun,Zhang, Zhebin,Fu, Zhengjiang,Cai, Hu
-
-
Read Online
- Facile preparation of 2-aryl-3-iodopyrroles with N-tosyl 4-aryl-3-butyn-1-ylamines, I2, andtBuOK
-
Treatment of N-tosyl 4-aryl-3-butyn-1-ylamines with I2 and K2CO3, followed by the reaction withtBuOK under mild conditions gave 2-aryl-3-iodopyrroles in good yields. The present approach is a one-pot method for the preparation of 2-aryl-3-iodopyrroles from N-tosyl 4-aryl-3-butyn-1-ylamines, which could be easily prepared from aryl iodides, N-(3-butyn-1-yl)phthalimides, and p-toluenesulfonyl chloride.
- Naruto, Hiroki,Shibasaki, Kaho,Togo, Hideo
-
p. 1091 - 1118
(2021/06/21)
-
- Asymmetric Alkylation of Ketones Catalyzed by Engineered TrpB
-
The β-subunit of tryptophan synthase (TrpB) catalyzes a PLP-mediated β-substitution reaction between indole and serine to form L-Trp. A succession of TrpB protein engineering campaigns to expand the enzyme's nucleophile substrate range has enabled the biocatalytic production of diverse non-canonical amino acids (ncAAs). Here, we show that ketone-derived enolates can serve as nucleophiles in the TrpB reaction to achieve the asymmetric alkylation of ketones, an outstanding challenge in synthetic chemistry. We engineered TrpB by directed evolution to catalyze the asymmetric alkylation of propiophenone and 2-fluoroacetophenone with a high degree of selectivity. In reactions with propiophenone, preference for the opposite product diastereomer emerges over the course of evolution, demonstrating that full control over the stereochemistry at the new chiral center can be achieved. The addition of this new reaction to the TrpB platform is a crucial first step toward the development of efficient methods to synthesize non-canonical prolines and other chirally dense nitrogen heterocycles.
- Arnold, Frances H.,Buller, Andrew R.,Dunham, Noah P.,Straathof, Sabine,Turi, Soma,Watkins-Dulaney, Ella J.
-
supporting information
p. 21412 - 21417
(2021/08/20)
-
- Synthesis of 1-Pyrroline by Denitrogenative Ring Expansion of Cyclobutyl Azides under Thermal Conditions
-
We herein report an efficient and systematic synthesis of 1-pyrrolines from cyclobutyl azides under thermal and neutral conditions. The reaction proceeded without any additional reagents, and nitrogen was generated as the sole by-product. Furthermore, the generated 1-pyrrolines could be continuously transformed into pyrroles, N-Boc-amines, and oxaziridines in an one-pot manner. (Figure presented.).
- Ban, Kazuho,Miki, Yuya,Sajiki, Hironao,Sawama, Yoshinari,Tomita, Naohito
-
supporting information
p. 3481 - 3484
(2021/06/17)
-
- Concurrent Formation of N-H Imines and Carbonyl Compounds by Ruthenium-Catalyzed C-C Bond Cleavage of β-Hydroxy Azides
-
A commercial cyclopentadienylrutenium dicarbonyl dimer ([CpRu(CO)2]2) efficiently catalyzes the formation of N-H imines and carbonyl compounds simultaneously from β-hydroxy azides via C-C bond cleavage under visible light. Density functional theory calculations for the cleavage reaction support the mechanism involving chelation of alkoxy azide species and liberation of nitrogen as the driving force. The synthetic utility of the reaction was demonstrated by a new amine synthesis promoted by chemoselective allylation of imine and synthesis of isoquinoline.
- Lee, Jeong Min,Bae, Dae Young,Park, Jin Yong,Jo, Hwi Yul,Lee, Eunsung,Rhee, Young Ho,Park, Jaiwook
-
p. 4608 - 4613
(2020/06/05)
-
- Arylation of indoles using cyclohexanones dually-catalyzed by niobic acid and palladium-on-carbons
-
3-Arylindoles were easily constructed from indoles and cyclohexanone derivatives using a combination of catalytic niobic acid-on-carbon (Nb2O5/C) and palladium-on-carbon (Pd/C) under heating conditions without any oxidants. The Lewis acidic Nb2O5/C promoted the nucleophilic addition of indoles to the cyclohexanones, and the subsequent dehydration and Pd/C-catalyzed dehydrogenation produced the 3-arylindoles. The additive 2,3-dimethyl-1,3-butadiene worked as a hydrogen acceptor to facilitate the dehydrogenation step.
- Ban, Kazuho,Sajiki, Hironao,Sawama, Yoshinari,Yamamoto, Yuta
-
supporting information
p. 3898 - 3902
(2020/06/03)
-
- General Transition Metal-Free Synthesis of NH-Pyrroles from Secondary Alcohols and 2-Aminoalcohols
-
A novel, transition metal-free and one-pot methodology to synthesize various substituted NH-pyrroles from readily available building blocks such as secondary alcohols and 2-aminoalcohols is described. The process is based on the venerable Oppenauer-Woodward oxidation, which uses benzophenone as an inexpensive reagent to achieve oxidation of secondary alcohols under mild condition to ketones, further in situ condensation with aminoalcohol, and oxidative cyclization to the target pyrrole ring. The reaction occurs under basic conditions, and features a broad substrate scope combined with very good tolerance for sensitive functional groups. This method can be used to synthesize various substituted pyrroles useful as a starting material for broad applications.
- Krasniqi, Besir,Geerts, Kayle,Dehaen, Wim
-
p. 5027 - 5034
(2019/05/10)
-
- C?H Arylation on Nickel Nanoparticles Monitored by In Situ Surface-Enhanced Raman Spectroscopy
-
Bifunctional Au@Ni core–satellite nanostructures synthesized by a one-step assembly method were employed for in situ surface-enhanced Raman spectroscopic (SERS) monitoring of Ni-catalyzed C?C bond-forming reactions. Surprisingly, the reaction that was thought to be an Ullmann-type self-coupling reaction, was found to be a cross-coupling reaction proceeding by photoinduced aromatic C?H bond arylation. In situ SERS monitoring enabled the discovery, and a series of biphenyl compounds were synthesized photocatalytically, and at room temperature, using cheap Ni nanoparticle catalysts.
- Li, Yonglong,Hu, Yanfang,Shi, Faxing,Li, Haixia,Xie, Wei,Chen, Jun
-
supporting information
p. 9049 - 9053
(2019/06/13)
-
- Identification of cb1 receptor allosteric sites using force-biased mmc simulated annealing and validation by structure-activity relationship studies
-
Positive allosteric modulation of the cannabinoid 1 receptor (CB1R) has demonstrated distinct therapeutic advantages that address several limitations associated with orthosteric agonism and has opened a promising therapeutic avenue for further drug development. To advance the development of CB1R positive allosteric modulators, it is important to understand the molecular architecture of CB1R allosteric site(s). The goal of this work was to use Force-Biased MMC Simulated Annealing to identify binding sites for GAT228 (R), a partial allosteric agonist, and GAT229 (S), a positive allosteric modulator (PAM) at the CB1R. Our studies suggest that GAT228 binds in an intracellular (IC) TMH1-2-4 exosite that would allow this compound to act as a CB1 allosteric agonist as well as a CB1 PAM. In contrast, GAT229 binds at the extracellular (EC) ends of TMH2/3, just beneath the EC1 loop. At this site, this compound can act as CB1 PAM only. Finally, these results were successfully validated through the synthesis and biochemical evaluation of a focused library of compounds.
- Hurst, Dow P.,Garai, Sumanta,Kulkarni, Pushkar M.,Schaffer, Peter C.,Reggio, Patricia H.,Thakur, Ganesh A.
-
p. 1216 - 1221
(2019/08/27)
-
- Generation of Aryl Radicals from Aryl Halides: Rongalite-Promoted Transition-Metal-Free Arylation
-
A new and practical method for the generation of aryl radicals from aryl halides is reported. Rongalite as a novel precursor of super electron donors was used to initiate a series of electron-catalyzed reactions under mild conditions. These transition-metal-free radical chain reactions enable the efficient formation of C-C, C-S, and C-P bonds through homolytic aromatic substitution or SRN1 reactions. Moreover, the synthesis of antipsychotic drug Quetiapine was performed on gram scale through the described method. This protocol demonstrated its potential as a promising arylation method in organic synthesis.
- Yu, Fazhi,Mao, Runyu,Yu, Mingcheng,Gu, Xianfeng,Wang, Yonghui
-
p. 9946 - 9956
(2019/09/04)
-
- Visible-Light Photocatalytic Preparation of 1,4-Ketoaldehydes and 1,4-Diketones from α-Bromoketones and Alkyl Enol Ethers
-
A Ru2+-photocatalyzed, visible-light-mediated ATRA reaction for the straightforward preparation of 1,4-ketoaldehydes, 1,4-diketones, and 1,4-ketoesters, which are of difficult access by other means, is reported herein. This method employs readily accessible α-bromoketones and alkyl vinyl ethers as starting materials, allowing the construction of secondary, tertiary, and challenging quaternary centers. In addition, the synthetic usefulness of this method is illustrated by applying it to the construction of substituted pyrroles.
- García-Santos, William H.,Mateus-Ruiz, Jeferson B.,Cordero-Vargas, Alejandro
-
supporting information
p. 4092 - 4096
(2019/06/17)
-
- Decarboxylative arylation of substituted pyrroles N -protected with 2-(trimethylsilyl)ethoxymethyl (SEM)
-
Palladium-catalyzed decarboxylative arylation is reported using pyrroles N-protected with the 2-(trimethylsilyl)ethoxymethyl (SEM) group and featuring 2-, 3-, and 4-substituents about the pyrrolic framework. In contrast to N-protected pyrroles previously
- Figliola, Carlotta,Greening, Sarah M.,Lamont, Connor,Groves, Brandon R.,Thompson, Alison
-
p. 534 - 542
(2018/06/07)
-
- GRP94 SELECTIVE INHIBITORS AND USES THEREOF
-
The present technology provides compounds according to Formula I or Formula III as well as compositions including such compounds useful for the treatment of metastatic cancer and/or glaucoma.
- -
-
Paragraph 0113; 0114
(2018/05/24)
-
- Isolation and identification of the pre-catalyst in iron-catalyzed direct arylation of pyrrole with phenylboronic acid
-
Herein we describe the synthesis, characterization, and role of three dichloric iron(III) complexes, [L1Fe(III)(Cl)2]ClO4 (L1Fe), [L2Fe(III)(Cl)2]ClO4 (L2Fe), and [L3Fe(III)(Cl)2]ClO4 (L3Fe
- Brewer, Samantha M.,Palacios, Philip M.,Johnston, Hannah M.,Pierce, Brad S.,Green, Kayla N.
-
p. 139 - 147
(2018/04/17)
-
- Catalytic C-Alkylation of Pyrroles with Primary Alcohols: Hans Fischer's Alkali and a New Method with Iridium P,N,P-Pincer Complexes
-
Hydrogen-autotransfer alkylation (HAT or “borrowing-hydrogen” alkylation) of heteroaromatic compounds has been studied with a range of substrates recently, but pyrroles have been largely absent from such studies. The conditions for HAT alkylations of pyrroles were investigated under a variety of conditions and were found to take place under basic alcoholic conditions (Hans Fischer alkylation) in the absence of transition-metal catalysts; by means of a heterogeneous Pd/C catalyst in the presence of base; and finally by means of homogeneous transition-metal catalysis combining a base and iridium pincer complexes generated in situ that have not previously been used in HAT alkylations of heterocycles.
- Koller, Sebastian,Blazejak, Max,Hintermann, Lukas
-
p. 1624 - 1633
(2018/04/24)
-
- Synthesis of 5-Arylpyrrole-2-carboxylic Acids as Key Intermediates for NBD Series HIV-1 Entry Inhibitors
-
5-Arylpyrrole-2-carboxylic acids are important key intermediates in the synthesis of HIV-1 entry inhibitors (such as NBD-11021 and NBD-14010). Here we present a general method for the synthesis of some 5-arylpyrrole-2-carboxylic acids in three steps starting from pyrrole. By this method, the compounds could be prepared on gram scale and without chromatographic purification.
- Belov, Dmitry S.,Ivanov, Vladimir N.,Curreli, Francesca,Kurkin, Alexander V.,Altieri, Andrea,Debnath, Asim K.
-
p. 3692 - 3699
(2017/08/15)
-
- Transition-Metal-Free C3 Arylation of Indoles with Aryl Halides
-
We report an unprecedented transition metal-free coupling of indoles with aryl halides. The reaction is promoted by KOtBu and is regioselective for C3 over N. The use of degassed solvents devoid of oxygen is necessary for the success of the transformation. Preliminary studies implicate a hybrid mechanism that involves both aryne intermediates and non-propagative radical processes. Electron transfer is also a distinct possibility. These conclusions were substantiated by EPR data, isotopic labeling studies, and the use of radical scavengers and electron transfer inhibitors.
- Chen, Ji,Wu, Jimmy
-
supporting information
p. 3951 - 3955
(2017/03/27)
-
- Selective aryl radical transfers into N-heteroaromatics from diaryliodonoium salts with trimethoxybenzene auxiliary
-
We have found that a series of trimethoxybenzene-based diaryliodonium(III) salts I (ArI+Ar’X-, where Ar = various aryl groups, Ar’ = 2,4,6-trimethoxyphenyl, X- = counterion) can exclusively cause Ar-transfers during the base-induced radical couplings with N-heteroaromatic compounds 1 by working the trimethoxybenzene ring (Ar’) as an inert coupling auxiliary. By the treatment with N-heteroaromatics 1 as the solvent, the metal-free arylations utilizing the specific salts I initiated by solid NaOH upon heating selectively produced the corresponding biaryls 2 in good yields without the formation of the trimethoxybenzene (Ar’) coupling product.
- Dohi, Toshifumi,Ueda, Shohei,Hirai, Akiko,Kojima, Yusuke,Morimoto, Koji,Kita, Yasuyuki
-
p. 1272 - 1284
(2019/11/14)
-
- Isomer-Specific Hydrogen Bonding as a Design Principle for Bidirectionally Quantitative and Redshifted Hemithioindigo Photoswitches
-
A new class of bidirectionally quantitative photoswitches based on the hemithioindigo (HTI) scaffold is reported. Incorporation of a pyrrole hydrogen-bond donor leads to a bathochromic shift allowing for quantitative bidirectional isomerization. Additionally, extending conjugation from the electron-rich pyrrole results in quantitative visible-light photoswitches, as well as photoswitches that isomerize with red and near-infrared light. The presence of the hydrogen bond leading to the observed redshift is supported by computational and spectroscopic evidence.
- Zweig, Joshua E.,Newhouse, Timothy R.
-
p. 10956 - 10959
(2017/08/21)
-
- Substituted pyrrole synthesis from nitrodienes
-
Though the Cadogan-Sundberg approach has been employed to synthesize a variety of indole and carbazole derivatives from nitroarenes, surprisingly, very little is reported for making pyrroles using the same approach from non-arene nitrodienes. Herein, we report a general method to synthesize substituted pyrroles, in one step with modest yields, from nitrodienes using triphenylphosphine in the presence of an Mo catalyst, bis(acetylaceto)dioxomolybdenum (VI). To shed light on the mechanism of this reaction, we performed DFT calculations using uB3LYP/6-31+G(d) basis set and observed that the reaction favors a path through a nitrene intermediate.
- Karimi, Sasan,Ma, Shuai,Liu, Yanan,Ramig, Keith,Greer, Edyta M.,Kwon, Kitae,Berkowitz, William F.,Subramaniam, Gopal
-
p. 2223 - 2227
(2017/05/16)
-
- Selective synthesis of pyrrolo[1,2-a] azepines or 4,6-dicarbonyl indoles via tandem reactions of alkynones with pyrrole derivatives
-
Novel methodologies for the selective synthesis of pyrrolo[1,2-a]azepines or 4,6-dicarbonyl indoles starting from pyrrole derivatives and alkynones are described. When reactions were carried out with 1,2,4-trisubstituted N-propargyl pyrroles using a ZnI2 catalyst, pyrrolo[1,2-a]azepines were obtained. Whereas 4,6-dicarbonyl indoles were produced selectively with 1,2-disubstituted pyrroles in the presence of silica gel. The reaction outcomes depend on the substituent pattern of the substrates and the nature of the catalysts chosen. Control reactions suggested that the formation of a conjugated enamine intermediate was crucial for both the processes. With easily accessible starting materials, inexpensive catalysts and an easy-to-handle procedure, this reaction has the potential to become a general protocol for the synthesis of pyrrolo[1,2-a]azepines or indoles.
- Zhao, Yulei,Yuan, Yang,Xu, Murong,Zheng, Zhong,Zhang, Runhua,Li, Yanzhong
-
supporting information
p. 6328 - 6332
(2017/08/10)
-
- Integration of oxidative arylation with sulfonyl migration: One-pot tandem synthesis of densely functionalized (NH)-pyrroles
-
A one-pot synthesis of 2-aryl-3-alkyl/aryl-sulfonyl-(NH)-pyrroles from N-sulfonylpyrroles, developed for the first time, via palladium-catalyzed oxidative C-2 arylation followed by sulfonyl migration is described. The simple, easy access to the highly functionalized free-NH pyrroles secures opportunities for the preparation of compounds with promising biological activities in contemporary organic synthesis. The event of sulfonyl migration from pyrrole-N to C-3 is thermodynamically favored as revealed by density functional methods. The different plausible mechanisms for the migration of the sulfonyl group are also discussed.
- Laha, Joydev K.,Sharma, Shubhra,Bhimpuria, Rohan A.,Dayal, Neetu,Dubey, Gurudutt,Bharatam, Prasad V.
-
p. 8791 - 8803
(2017/08/29)
-
- Transformation of the non-selective aminocyclohexanol-based Hsp90 inhibitor into a Grp94-seletive scaffold
-
Glucose regulated protein 94 kDa, Grp94, is the endoplasmic reticulum (ER) localized isoform of heat shock protein 90 (Hsp90) that is responsible for the trafficking and maturation of toll-like receptors, immunoglobulins, and integrins. As a result, Grp94 has emerged as a therapeutic target to disrupt cellular communication, adhesion, and tumor proliferation, potentially with fewer side effects compared to pan-inhibitors of all Hsp90 isoforms. Although, the N-terminal ATP binding site is highly conserved among all four Hsp90 isoforms, recent cocrystal structures of Grp94 have revealed subtle differences between Grp94 and other Hsp90 isoforms that has been exploited for the development of Grp94-selective inhibitors. In the current study, a structure-based approach has been applied to a Grp94 nonselective compound, SNX 2112, which led to the development of 8j (ACO1), a Grp94-selective inhibitor that manifests -440 nM affinity and ≥200-fold selectivity against cytosolic Hsp90 isoforms.
- Mishra, Sanket J.,Ghosh, Suman,Stothert, Andrew R.,Dickey, Chad A.,Blagg, Brian S. J.
-
p. 244 - 253
(2017/12/30)
-
- Dehydrogenation of 2-Phenyl-1-pyrroline with Palladium-Supported Catalysts: An Effective Route to the Synthesis of 2-Phenylpyrrole
-
The catalytic dehydrogenation of 5-phenyl-3,4-dihydro-2H-pyrrole (2-phenyl-1-pyrroline) to 2-phenyl-1H-pyrrole in the presence of palladium-supported on activated carbon (Pd/C) or on alumina (Pd/Al2O3) is reported. Highly pure 2-phenylpyrrole is obtained in good yields and selectivities, in a ca. 20 gram-scale, after a simple work-up. The Pd/Al2O3 catalyst exhibited substantially higher activities than the Pd/C ones. (Figure Presented).
- Figueira, Cludia A.,Gomes, Pedro T.
-
p. 762 - 768
(2015/08/06)
-
- Synthesis of 2-arylpyrroles via catalytic dehydrogenation of 2-aryl-1-pyrrolines in the presence of palladium-supported on alumina
-
A convenient synthesis of 2-arylpyrroles from the catalytic dehydrogenation of 2-aryl-1-pyrrolines in the presence of commercial palladium-supported on alumina (Pd/Al2O3) is described. The reaction scope was tested for aryl substituents with different steric hindrances and electronic natures. The dehydrogenation reaction conditions such as temperature, reflux time and amount of catalyst, revealed to be highly dependent on the 2-aryl substituent group, moderate to high yields and selectivities being obtained in a reaction involving straightforward work-up and purification procedures. In addition, the synthesis of the corresponding 2-aryl-1-pyrroline starting materials, through the cyclisation reaction involving 4-chlorobutyronitrile and aryl Grignard reagents, is also reported.
- Figueira, Cláudia A.,Lopes, Patrícia S.,Gomes, Pedro T.
-
p. 4362 - 4371
(2015/06/08)
-
- Expedient one-pot synthesis of pyrroles from ketones, hydroxylamine, and 1,2-dichloroethane
-
2- and 2,3-Substituted pyrroles are readily synthesized in a one-pot procedure from ketones, hydroxylamine hydrochloride, and 1,2-dichloroethane in the KOH/DMSO system (120 °C, 2-4 h), the yields of pyrroles ranging 11-85%. Aliphatic, cycloaliphatic, aromatic, and heteroaromatic ketones tolerate the reaction conditions.
- Trofimov, Boris A.,Mikhaleva, Al'Bina I.,Ivanov, Andrei V.,Shcherbakova, Viktoria S.,Ushakov, Igor A.
-
p. 124 - 128
(2015/02/02)
-
- Direct synthesis of aryl substituted pyrroles from calcium carbide: An underestimated chemical feedstock?
-
In this work, a novel synthetic methodology for the preparation of aryl pyrroles directly from the reaction of calcium carbide with oxime is reported. Various pyrrole derivatives are generated from the corresponding oximes in satisfactory yields (49–88%) under the optimized conditions. The one-pot synthesis of aryl pyrrole from widely available ketone is also successfully developed. A new near-infrared fluorescent BODIPY dye containing a phenyl substitution at the C-3 position is expediently prepared from the aryl pyrrole derived from this methodology. The key benefit of this methodology is the use of an inexpensive and less hazardous primary chemical feedstock, calcium carbide, in a wet solvent without any metal catalysts. This process offers a novel cost-efficient route for the synthesis of functionalized pyrrole.
- Kaewchangwat, Narongpol,Sukato, Rangsarit,Vchirawongkwin, Viwat,Vilaivan, Tirayut,Sukwattanasinitt, Mongkol,Wacharasindhu, Sumrit
-
p. 460 - 465
(2018/04/16)
-
- Transition-metal-free trifluoromethylthiolation of n-heteroarenes
-
A general and efficient methodology for the direct transition metal free trifluoromethylthiolation of a broad range of biologically relevant N-heteroarenes is reported employing abundant sodium chloride as the catalyst. This method is operationally simple, exhibits high functional group tolerance, and does not require protecting groups. A pinch of salt: A general and efficient methodology for the direct transition-metal-free trifluoromethylthiolation of a broad range of biologically relevant N-heteroarenes is reported employing abundant sodium chloride as the catalyst. This method is operationally simple, exhibits high functional group tolerance, and does not require protecting groups.
- Honeker, Roman,Ernst, Johannes B.,Glorius, Frank
-
supporting information
p. 8047 - 8051
(2015/05/27)
-
- Increased photocurrent in a tandem dye-sensitized solar cell by modifications in push-pull dye-design
-
Donor-π-acceptor photosensitizers for NiO photocathodes that exhibit a broad spectral response across the visible region are presented. These enabled an increase in the photocurrent density of p-type dye-sensitized solar cells to 8.2 mA cm-2 and a tandem cell to be assembled which generated a photocurrent density of 5.15 mA cm-2.
- Wood,Summers,Gibson
-
supporting information
p. 3915 - 3918
(2015/03/18)
-
- Copper-catalyzed 5-endo-trig cyclization of ketoxime carboxylates: A facile synthesis of 2-arylpyrroles
-
A novel and facile copper-catalyzed 5-endo-trig cyclization of ketoxime carboxylates for the synthesis of 2-arylpyrroles has been developed. The reaction tolerates a range of functional groups and is a practical procedure for rapid synthesis of 2-arylpyrroles in high yields under mild conditions. the Partner Organisations 2014.
- Du, Wei,Zhao, Mi-Na,Ren, Zhi-Hui,Wang, Yao-Yu,Guan, Zheng-Hui
-
p. 7437 - 7439
(2014/07/07)
-
- Organocatalytic enantioselective multicomponent synthesis of pyrrolopiperazines
-
The first organocatalytic multicomponent synthesis of enantioenriched pyrrolopiperazines is reported. These biologically relevant fused tricyclic products were obtained under catalytic iminium activation through a reaction sequence involving an enantioselective Michael addition followed by an iminium ion trapping via Pictet-Spengler cyclization (MAPS sequence). Substantial possibilities for variation on the three reaction partners [β-keto ester, enal and N-(2-aminoethyl)pyrrole] along with excellent enantioselectivities are the highlights of the present transformation.
- Du, Haiying,Rodriguez, Jean,Bugaut, Xavier,Constantieux, Thierry
-
p. 851 - 856
(2014/04/03)
-
- One-pot synthesis of pyrroles from ketones, hydroxylamine, and 1,2-dibromoethane in the system KOH-DMSO
-
Dibutyl ketone, cyclohexanone, acetophenone, α-tetralone, and methyl 2-thienyl ketone were converted into the corresponding 2,3-substituted pyrroles by reaction with hydroxylamine hydrochloride and 1,2-dibromoethane in the system KOH-DMSO.
- Ivanov, A. V.,Shcherbakova, V. S.,Mikhaleva, A. I.,Trofimov, B. A.
-
p. 1775 - 1778
(2015/02/05)
-
- Visible-light sensitization of vinyl azides by transition-metal photocatalysis
-
Irradiation of vinyl and aryl azides with visible light in the presence of Ru photocatalysts results in the formation of reactive nitrenes, which can undergo a variety of C-N bond-forming reactions. The ability to use low-energy visible light instead of UV in the photochemical activation of azides avoids competitive photodecomposition processes that have long been a significant limitation on the synthetic use of these reactions. Rock and pyrrole: Irradiation of vinyl and aryl azides with visible light in the presence of Ru photocatalysts results in the formation of reactive nitrenes, which can undergo a variety of C-N bond-forming reactions. The ability to use low-energy visible light instead of UV in the photochemical activation of azides (see picture) avoids competitive photodecomposition processes. Copyright
- Farney, Elliot P.,Yoon, Tehshik P.
-
supporting information
p. 793 - 797
(2014/01/23)
-
- Rhodium-catalyzed decarbonylative direct C2-arylation of indoles with aryl carboxylic acids
-
A RhI-catalyzed direct C2-arylation of indoles with diversely substituted aryl carboxylic acids has been developed using 2-pyrimidyl group as an easily installable and readily removable N-directing group. The reaction proceeded smoothly without the need for any external oxidants under relatively mild conditions to produce the C2-arylated indoles in high yields with excellent regioselectivity. A range of functional groups in both coupling partners were tolerated regardless of their electronic properties and positions. With the assistance of the 2-pyrimidyl group, these C2-functionalized products could further undergo C7-arylation to give the C7-aryl indole products. Mechanistic evidence supports that the reaction involves a decarbonylation step, and the carboxylic acids could be activated in situ by treatment with (tBuCO)2O to generate the active anhydrides.
- Zhang, Lingjuan,Xue, Xiao,Xu, Conghui,Pan, Yixiao,Zhang, Guang,Xu, Lijin,Li, Huanrong,Shi, Zhangjie
-
p. 3069 - 3074
(2015/02/02)
-
- Synthesis and optical properties of difluorobora-s-diazaindacene dyes with trifluoromethyl meso-substituents
-
A series of meso-CF3-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes with aryl and hetaryl substituents at the C-3 and C-5 positions, both symmetric and asymmetric, have been synthesized in 36-90 % yields by a new strategy involving as the key step the condensation of 2,2,2-trifluoro-1-(5- arylpyrrol-2-yl)-1-ethanols with diverse 2-arylpyrroles. The starting 2,2,2-trifluoro-1-(5-arylpyrrol-2-yl)-1-ethanols are easily prepared by reduction of the available 2-trifluoroacetyl-5-arylpyrroles. The synthesized dyes fluoresce in a longer wavelength region (626-698 nm) with high quantum yield (0.84-0.99). A new strategy for the synthesis of highly efficient symmetric and asymmetric BODIPY fluorophores that combine trifluoromethyl and 3,5-aryl substituents has been developed. The key step is the P 2O5-promoted condensation of 2,2,2-trifluoro-1-(5- arylpyrrol-2-yl)-1-ethanols with diverse 2-arylpyrroles. Copyright
- Sobenina, Lyubov N.,Petrova, Olga V.,Petrushenko, Konstantin B.,Ushakov, Igor A.,Mikhaleva, Albina I.,Meallet-Renault, Rachel,Trofimov, Boris A.
-
p. 4107 - 4118
(2013/07/19)
-
- Visible light-mediated direct arylation of arenes and heteroarenes using diaryliodonium salts in the presence and absence of a photocatalyst
-
Diaryliodonium salts have been used as aryl radical sources under visible light-mediated photoredox catalysis. Benzene and a range of heteroarenes are arylated with Ar2I+ in the presence of [Ir(ppy)2(bpy)] PF6 upon irradiation with visible light. When pyrroles are used, the arylation proceeds in the absence of a photoredox catalyst. Both processes are initiated by photoinduced single-electron-transfer to Ar2I+, generating aryl radicals.
- Tobisu, Mamoru,Furukawa, Takayuki,Chatani, Naoto
-
supporting information
p. 1203 - 1205
(2013/10/22)
-
- Expedient one-step synthesis of nitrogen stilbene analogs by transition metal-free hydroamination of arylacetylenes with pyrroles
-
A novel family of nitrogen stilbene analogs, 1-styrylpyrroles, has been synthesized in good to excellent yields by a straightforward facile transition metal-free addition of pyrroles to arylacetylenes in the KOH/DMSO system (90-120 °C, 5-13 h). Thermodynamically controlled E/Z-isomer ratio of 1-styrylpyrroles depends on structure of both pyrroles and acetylenes ranging from ca. 100% E-stereoselectivity (for the pair unsubstituted pyrrole - phenylacetylene) to 90, 96% Z-stereoselectivity (for the pairs: 2-phenylpyrrole - phenylacetylene and 2-(2-thienyl)pyrrole - phenylacetylene, respectively).
- Dvorko, Marina Yu.,Schmidt, Elena Yu.,Glotova, Tatyana E.,Shabalin, Dmitrii A.,Ushakov, Igor A.,Kobychev, Vladimir B.,Petrushenko, Konstantin B.,Mikhaleva, Al'Bina I.,Trofimov, Boris A.
-
body text
p. 1963 - 1971
(2012/03/22)
-
- Catalytic C-H arylation of unactivated heteroaromatics with aryl halides by cobalt porphyrin
-
Direct C-H arylation of unactivated heteroaromatics with aryl halides catalyzed by cobalt porphyrin is reported. The reaction is proposed to go through a homolytic aromatic substitution reaction. The aryl radical is electrophilic and a SOMO-HOMO interaction is predominant in the aryl radical addition process.
- Qian, Ying Ying,Wong, Ka Lai,Zhang, Meng Wen,Kwok, Tsz Yiu,To, Ching Tat,Chan, Kin Shing
-
supporting information; experimental part
p. 1571 - 1575
(2012/04/11)
-
- Direct arylation of arene and N -heteroarenes with diaryliodonium salts without the use of transition metal catalyst
-
A novel and simple transition metal-free direct arylation of arene and N-heteroarenes with diaryliodonium salts has been developed. This cross-coupling reaction is promoted only by base and gives the desired products in moderate to good yields.
- Wen, Jun,Zhang, Ruo-Yi,Chen, Shan-Yong,Zhang, Ji,Yu, Xiao-Qi
-
experimental part
p. 766 - 771
(2012/02/16)
-
- General route to symmetric and asymmetric meso -CF3-3(5)- aryl(hetaryl)- and 3,5-diaryl(dihetaryl)-BODIPY dyes
-
A general efficient route to hitherto inaccessible symmetric and asymmetric meso-CF3-BODIPY dyes has been developed. The key stages include the reduction of available 2-trifluoroacetylpyrroles to the corresponding alcohols which are further condensed with pyrroles. The method allows the BODIPY with 3(5)aryl(hetaryl) and 3,5-diaryl(hetaryl) substituents to be readily assembled. The BODIPY dyes synthesized fluoresce (?f = 0.56-1.00) in the 560-680 nm region.
- Sobenina, Lubov N.,Vasiltsov, Alexander M.,Petrova, Olga V.,Petrushenko, Konstantin B.,Ushakov, Igor A.,Clavier, Gilles,Meallet-Renault, Rachel,Mikhaleva, Albina I.,Trofimov, Boris A.
-
supporting information; experimental part
p. 2524 - 2527
(2011/06/25)
-
- Optimization of the Suzuki coupling reaction in the synthesis of 2-[(2-substituted)phenyl]pyrrole derivatives
-
A facile three-step synthesis of 2-(2-aminophenyl)pyrrole (1) and 2-[(2-aminomethyl)phenyl]pyrrole (2) is reported by use of Suzuki coupling of N-Boc-pyrrol-2-yl boronic acid (3) and o-substituted aryl halogenides, followed by hydrogenation. The Pd-catalyzed cross-coupling reaction is optimized to be applicable to a wide range of substitued aryl halogenides, with electron-donating and electron-withdrawing substituents, 5a-g. Moreover, Pd-catalyzed coupling of o-bromoaniline and 3 could be applied for the one-step preparation of pyrrolo[1,2-c]quinazolin-5(6H)-one (8). Copyright
- Aleskovic, Marija,Basaric, Nikola,Mlinaric-Majerski, Kata
-
experimental part
p. 1329 - 1335
(2012/01/04)
-
- An efficient pyrrole synthesis via silaphenylmercuric triflate catalyzed cyclization of homopropargyl azides
-
A mixture of phenylmercuric acetate and trifluoromethanesulfonic acid or silica gel supported phenylmercuric tri-fluoromethanesulfonate (silaphenyl mercuric triflate) efficiently catalyzed the formation of pyrroles from homopropargyl azide derivatives. The reactions proceed using 20 mol% of the heterogeneous catalyst with yields of isolated pyrroles ranging from 74% to 99%. Georg Thieme Verlag Stuttgart · New York.
- Yamamoto, Hirofumi,Sasaki, Ikuo,Mitsutake, Mizuho,Karasudani, Ayumi,Imagawa, Hiroshi,Nishizawa, Mugio
-
supporting information; experimental part
p. 2815 - 2818
(2012/01/05)
-
- Triethanolamine-mediated palladium-catalyzed regioselective C-2 direct arylation of free NH-pyrroles
-
An atom-economical phosphane-free palladium-catalyzed direct C-2 arylation of unactivated free NH-pyrroles is devised. This method provides a straithforward route to a wide variety of substituted 2-aryl-1H-pyrroles from readily accessible starting materials. Iodoarenes bearing electron-withdrawing and electron-donating substituents are tolerated under the presented reaction conditions. The scope of the reaction is also expanded to N-aryl and -alkylpyrroles albeit in lower yields.
- Jafarpour, Farnaz,Rahiminejadan, Soraya,Hazrati, Hamideh
-
supporting information; experimental part
p. 3109 - 3112
(2010/07/15)
-
- Rhodium(III)-catalyzed arene and alkene C-H bond functionalization leading to indoles and pyrroles
-
Recently, the rhodium(III)-complex [Cp*RhCl2]2 1 has provided exciting opportunities for the efficient synthesis of aromatic heterocycles based on a rhodium-catalyzed C-H bond functionalization event. In the present report, the use of complexes 1 and its dicationic analogue [Cp*Rh(MeCN)3][SbF6]2 2 have been employed in the formation of indoles via the oxidative annulation of acetanilides with internal alkynes. The optimized reaction conditions allow for molecular oxygen to be used as the terminal oxidant in this process, and the reaction may be carried out under mild temperatures (60 °C). These conditions have resulted in an expanded compatibility of the reaction to include a range of new internal alkynes bearing synthetically useful functional groups in moderate to excellent yields. The applicability of the method is exemplified in an efficient synthesis of paullone 3, a tetracyclic indole derivative with established biological activity. A mechanistic investigation of the reaction, employing deuterium labeling experiments and kinetic analysis, has provided insight into issues of reactivity for both coupling partners as well as aided in the development of conditions for improved regioselectivity with respect to meta-substituted acetanilides. This reaction class has also been extended to include the synthesis of pyrroles. Catalyst 2 efficiently couples substituted enamides with internal alkynes at room temperature to form trisubstituted pyrroles in good to excellent yields. The high functional group compatibility of this reaction enables the elaboration of the pyrrole products into a variety of differentially substituted pyrroles.
- Stuart, David R.,Alsabeh, Pamela,Kuhn, Michelle,Fagnou, Keith
-
p. 18326 - 18339
(2011/03/21)
-
- Slow magnetic relaxation in a family of trigonal pyramidal iron(II) pyrrolide complexes
-
We present a family of trigonal pyramidal iron(II) complexes supported by tris(pyrrolyl-α-methyl)amine ligands of the general formula [M(solv) n][(tpaR)Fe] (M = Na, R = tert-butyl (1), phenyl (4); M = K, R = mesityl (2), 2,4,6-triisopropylphenyl (3), 2,6-difluorophenyl (5)) and their characterization by X-ray crystallography, Moessbauer spectroscopy, and high-field EPR spectroscopy. Expanding on the discovery of slow magnetic relaxation in the recently reported mesityl derivative 2, this homologous series of high-spin iron(II) complexes enables an initial probe of how the ligand field influences the static and dynamic magnetic behavior. Magnetization experiments reveal large, uniaxial zero-field splitting parameters of D = -48, -44, -30, -26, and -6.2 cm-1 for 1-5, respectively, demonstrating that the strength of axial magnetic anisotropy scales with increasing ligand field strength at the iron(II) center. In the case of 2,6-difluorophenyl substituted 5, high-field EPR experiments provide an independent determination of the zero-field splitting parameter (D = -4.397(9) cm-1) that is in reasonable agreement with that obtained from fits to magnetization data. Ac magnetic susceptibility measurements indicate field-dependent, thermally activated spin reversal barriers in complexes 1, 2, and 4 of Ueff = 65, 42, and 25 cm-1, respectively, with the barrier of 1 constituting the highest relaxation barrier yet observed for a mononuclear transition metal complex. In addition, in the case of 1, the large range of temperatures in which slow relaxation is observed has enabled us to fit the entire Arrhenius curve simultaneously to three distinct relaxation processes. Finally, zero-field Moessbauer spectra collected for 1 and 4 also reveal the presence of slow magnetic relaxation, with two independent relaxation barriers in 4 corresponding to the barrier obtained from ac susceptibility data and to the 3D energy gap between the MS = ±2 and ±1 levels, respectively.
- Harman, W. Hill,Harris, T. David,Freedman, Danna E.,Fong, Henry,Chang, Alicia,Rinehart, Jeffrey D.,Ozarowski, Andrew,Sougrati, Moulay T.,Grandjean, Fernande,Long, Gary J.,Long, Jeffrey R.,Chang, Christopher J.
-
scheme or table
p. 18115 - 18126
(2011/02/28)
-
- A study of 1,2-dihydro-1,2-azaborine in a π-conjugated system
-
The reaction of N-Boc-protected bis(5-phenyl-2-pyrrolyl)borane with BF 3·OEt2 produced 3-(phenylpyrrolyl)-6-phenyl-1,2- dihydro-1,2-azaborine in moderate yield. This compound showed an absorption band at a longer wavelength compared to that of its benzene analogue and also exhibited an intense red-shifted fluorescence with a high quantum yield close to unity. According to the X-ray structural analysis, cyclic voltammetry, and theoretical calculations, the 1,2-dihydro-1,2-azaborine acts not like a benzene analogue but like a cyclohexadiene analogue in the extended π-conjugated skeleton.
- Taniguchi, Takuhiro,Yamaguchi, Shigehiro
-
experimental part
p. 5732 - 5735
(2011/02/17)
-