- Polar Effects in Free-Radical Reactions. Homolytic Heteroaromatic Substitutions by Alkyl Bromides
-
Alkyl bromides have been utilized for the first time as radical sources for heteroaromatic substitution.A variety of procedures was revealed to be successful for bromine abstraction: Bu3SnH with AIBN, (Me3Si)3SiH with AIBN, Ph2SiH2, or Et3SiH associated with peroxides (H2O2, t-BuOOH, (t-BuO)2, (t-BuOOCO)2, (PhCOO)2).The importance of the polar effects is discussed.
- Minisci, Francesco,Fontana, Francesca,Pianese, Guiseppe,Yan, Yong Ming
-
-
Read Online
- Minisci-Type Alkylation of N-Heteroarenes by N-(Acyloxy)phthalimide Esters Mediated by a Hantzsch Ester and Blue LED Light
-
A synthetic method that enables the Hantzsch ester-mediated Minisci-type C2-alkylation of quinolines, isoquinolines and pyridines by N-(acyloxy)phthalimide esters (NHPI) under blue LED (light emitting diode) light (456 nm) is described. Achieved under mild reaction conditions at room temperature, the metal-free synthetic protocol was shown to be applicable to primary, secondary and tertiary NHPIs to give the alkylated N-heterocyclic products in yields of 21–99%. On introducing a chiral phosphoric acid, an asymmetric version of the reaction was also realised and provided product enantiomeric excess (ee) values of 53–99%. The reaction mechanism was delineated to involve excitation of an electron-donor acceptor (EDA) complex, formed from weak electrostatic interactions between the Hantzsch ester and NHPI, which generates the posited radical species of the redox active ester that undergoes addition to the N-heterocycle.
- Li, Jiacheng,Siang Tan, Suan,Kyne, Sara Helen,Wai Hong Chan, Philip
-
p. 802 - 810
(2022/01/11)
-
- Visible-light-mediated photoredox minisci C-H alkylation with alkyl boronic acids using molecular oxygen as an oxidant
-
Herein, we report a protocol for direct visible-light-mediated Minisci C-H alkylation reactions of heteroarenes with alkyl boronic acids using molecular oxygen as the sole oxidant. This mild protocol uses an inexpensive, green oxidant; permits efficient functionalization of various N-heteroarenes with a broad range of primary and secondary alkyl boronic acids; and is scalable to the gram level. We demonstrated the practicality and sustainability of the protocol by preparing or functionalizing several pharmaceuticals and natural products.
- Dong, Jianyang,Yue, Fuyang,Song, Hongjian,Liu, Yuxiu,Wang, Qingmin
-
supporting information
p. 12652 - 12655
(2020/11/02)
-
- Minisci C?H Alkylation of Heteroarenes Enabled by Dual Photoredox/Bromide Catalysis in Micellar Solutions**
-
Aromatic heterocycles are omnipresent structural motifs in various natural products, pharmaceuticals and agrochemicals. This work describes a photocatalytic Minisci-type C?H functionalization of heteroarenes with non-activated alkyl bromides. The reaction avoids stoichiometric radical-promoters, oxidants, or acids, and is conducted using blue LEDs as the light source. The reactive carbon-centered alkyl radicals are generated by merging the photoredox approach with bromide anion co-catalysis and spatial pre-aggregation of reacting species in the micellar aqueous solutions. The obtained data highlight the critical importance of microstructuring and organization of the components in the reaction mixture.
- Santos, Marilia S.,Cybularczyk-Cecotka, Martyna,K?nig, Burkhard,Giedyk, Maciej
-
supporting information
p. 15323 - 15329
(2020/10/26)
-
- Visible-Light-Mediated C-H Alkylation of Pyridine Derivatives
-
We report herein a visible-light-mediated C-H alkylation of pyridine derivatives that proceeds by simple combination of a large variety of N-alkoxypyridinium ions with alkanes in the presence of 2 mol % of fac-Ir(ppy)3 under blue illumination. The mild reaction conditions together with the high group functional tolerance make of this process a useful synthetic platform for the construction of structurally strained heterocycles. Detailed mechanistic investigations, including density functional theory calculations and quantum yield measurement, allowed us to understand factors controlling the reactivity and the selectivity of the reaction.
- Rammal, Fatima,Gao, Di,Boujnah, Sondes,Gaumont, Annie-Claude,Hussein, Aqeel A.,Lakhdar, Sami
-
p. 7671 - 7675
(2020/10/09)
-
- Preparation of 2-Arylquinolines from 2-Arylethyl Bromides and Aromatic Nitriles with Magnesium and N -Iodosuccinimide
-
Treatment of 2-arylethylmagnesium bromides, prepared from 2-arylethyl bromides and magnesium, with aromatic nitriles, followed by reaction with water and then with N -iodosuccinimide under irradiation with a tungsten lamp, gave the corresponding 2-arylquinolines in good to moderate yields under transition-metal-free conditions. 2-Alkylquinolines could be also obtained in moderate yields by the same procedure with 2-arylethyl bromides, magnesium, aliphatic nitriles bearing a secondary alkyl group, and N -iodosuccinimide.
- Naruto, Hiroki,Togo, Hideo
-
p. 1122 - 1130
(2020/04/01)
-
- Visible-light-mediated Minisci C-H alkylation of heteroarenes with unactivated alkyl halides using O2 as an oxidant
-
Herein, we report a protocol for direct visible-light-mediated Minisci C-H alkylation of heteroarenes with unactivated alkyl halides using molecular oxygen as an oxidant at room temperature. This mild protocol is compatible with a wide array of sensitive
- Dong, Jianyang,Lyu, Xueli,Wang, Zhen,Wang, Xiaochen,Song, Hongjian,Liu, Yuxiu,Wang, Qingmin
-
p. 976 - 982
(2019/02/03)
-
- Green synthesis of silver nanoparticles using green alga (Chlorella vulgaris) and its application for synthesis of quinolines derivatives
-
Nanoparticles have been used century ago but have regained their importance in recent years being simple, ecofriendly, pollutant free, nontoxic, low-cost approach, and due good atom economy. In this report, we have demonstrated the synthesis of silver nanoparticles using green algae (Chlorella vulgaris) which in turn was used for synthesis of biologically important quinolines. Algal extract was prepared and treated with silver nitrate solution for the synthesis of silver nanoparticles. Synthesized nanoparticles were characterized with the help of analytical tools like UV, FTIR, X-ray, and SEM and used as a catalyst for the synthesis of quinolines.
- Mahajan, Akhil,Arya, Anju,Chundawat, Tejpal Singh
-
supporting information
p. 1926 - 1937
(2019/05/17)
-
- A visible light-driven minisci-type reaction with N-hydroxyphthalimide esters
-
A visible light-promoted protocol for the redox-neutral coupling of N-hydroxyphthalimide esters with different N-heterocyclic compounds is described. The reaction proceeds through an alkyl radical intermediate generated by reductive decarboxylation of N-hydroxyphthalimide esters. In contrast to the original Minisci protocol, polyalkylation can largely be avoided. Mechanistic investigations revealed a radical chain mechanism which in some cases can proceed even if no photocatalyst is added. This valuable and functional group-tolerant reaction produces substituted heterocycles in moderate to excellent yield. The use of inexpensive starting materials and LEDs as the light source are key features of this C–C bond formation.
- Kammer, Lisa Marie,Rahman, Aliyaah,Opatz, Till
-
-
- Organocatalyzed, Visible-Light Photoredox-Mediated, One-Pot Minisci Reaction Using Carboxylic Acids via N-(Acyloxy)phthalimides
-
An improved, one-pot Minisci reaction has been developed using visible light, an organic photocatalyst, and carboxylic acids as radical precursors via the intermediacy of in situ-generated N-(acyloxy)phthalimides. The conditions employed are mild, demonstrate a high degree of functional group tolerance, and do not require a large excess of the carboxylic acid reactant. As a result, this reaction can be applied to drug-like scaffolds and molecules with sensitive functional groups, enabling late-stage functionalization, which is of high interest to medicinal chemistry.
- Sherwood, Trevor C.,Li, Ning,Yazdani, Aliza N.,Dhar, T. G. Murali
-
p. 3000 - 3012
(2018/03/09)
-
- Visible Light-Mediated Direct Decarboxylative C-H Functionalization of Heteroarenes
-
The direct visible light-mediated C-H alkylation of heteroarenes using aliphatic carboxylic acids is reported. This mild method proceeds at low catalyst loadings (0.5 mol %) and has a high functional group tolerance and a broad substrate scope. Notably, f
- Garza-Sanchez, R. Aleyda,Tlahuext-Aca, Adrian,Tavakoli, Ghazal,Glorius, Frank
-
p. 4057 - 4061
(2017/06/19)
-
- Visible-Light-Initiated Manganese Catalysis for C?H Alkylation of Heteroarenes: Applications and Mechanistic Studies
-
A visible-light-driven Minisci protocol that employs an inexpensive earth-abundant metal catalyst, decacarbonyldimanganese Mn2(CO)10, to generate alkyl radicals from alkyl iodides has been developed. This Minisci protocol is compatible with a wide array of sensitive functional groups, including oxetanes, sugar moieties, azetidines, tert-butyl carbamates (Boc-group), cyclobutanes, and spirocycles. The robustness of this protocol is demonstrated on the late-stage functionalization of complex nitrogen-containing drugs. Photophysical and DFT studies indicate a light-initiated chain reaction mechanism propagated by .Mn(CO)5. The rate-limiting step is the iodine abstraction from an alkyl iodide by .Mn(CO)5.
- Nuhant, Philippe,Oderinde, Martins S.,Genovino, Julien,Juneau, Antoine,Gagné, Yohann,Allais, Christophe,Chinigo, Gary M.,Choi, Chulho,Sach, Neal W.,Bernier, Louise,Fobian, Yvette M.,Bundesmann, Mark W.,Khunte, Bhagyashree,Frenette, Mathieu,Fadeyi, Olugbeminiyi O.
-
supporting information
p. 15309 - 15313
(2017/11/01)
-
- Blue-light-promoted carbon-carbon double bond isomerization and its application in the syntheses of quinolines
-
A blue-light-promoted carbon-carbon double bond isomerization in the absence of any photoredox catalyst is reported. It provides rapid access to a series of quinolines in good to excellent yields under simple aerobic conditions. The protocol is direct, catalyst-free and operationally convenient.
- Chen, Xinzheng,Qiu, Shuxian,Wang, Sasa,Wang, Huifei,Zhai, Hongbin
-
p. 6349 - 6352
(2017/08/10)
-
- Organocatalytic synthesis of methylene-bridged N-heterobiaryls
-
A one-step synthesis of 1,1′- and 2,2′-methylene-bridged N-heterobiaryls directly from the corresponding N-heterocycles in a reaction with methylmagnesium chloride in the presence of catalytic amounts of N,N,N′,N′-tetramethylethylenediamine under thermal and microwave conditions is reported. The split-and-merge methylenation of 2,2′-N-heterobiaryls and the direct ortho-alkylation of quinoline and isoquinoline with Grignard reagents have also been developed. Mechanistic studies identified several intermediates and provided insight into the formation and roles of magnesium hydride species in the process.
- Stephens, David E.,Nguyen, Vu T.,Chhetri, Bhuwan,Clark, Emily R.,Arman, Hadi D.,Larionov, Oleg V.
-
supporting information
p. 5808 - 5811
(2016/11/29)
-
- Silver-catalyzed three-component approach to quinolines starting from anilines, aldehydes, and alcohols
-
A silver-catalyzed sequential formation of two C-C bonds for the construction of a series of polysubstituted quinolines from anilines, aldehydes, and alcohols under mild conditions has been developed. The transformation is effective for a broad range of substrates, including aliphatic alcohols, arylalkanols, cycloalkanols, and ethylene glycol, thereby permitting the expansion of the constituent architectures of the heterocyclic framework.
- Zhang, Xu,Liu, Wenmin,Sun, Ruixue,Xu, Xuefeng,Wang, Zhiqiang,Yan, Yanlei
-
p. 1563 - 1568
(2016/06/14)
-
- Benzoyl peroxide promoted radical ortho-alkylation of nitrogen heteroaromatics with simple alkanes and alcohols
-
A catalytic amount of benzoyl peroxide (BPO)-initiated cross-dehydrogenative coupling reaction of N-iminopyridine ylides with simple alkanes and alcohols leads to the corresponding 2-alkylpyridines with high regioselectivity in moderate to good yields without an additional reduction step to remove the activated group. A catalytic amount of benzoyl peroxide (BPO)-initiated cross-dehydrogenative coupling reaction of N-iminopyridine ylides with simple alkanes and alcohols has been developed. The strategy allowed convenient access to various 2-alkylpyridines in moderate to good yields without an additional reduction step to remove the activated group.
- Fang, Lei,Chen, Liangshun,Yu, Jianjun,Wang, Limin
-
p. 1910 - 1914
(2015/03/18)
-
- Synthesis of 2-substituted quinolines from alcohols
-
A facile and economic method for the construction of 2-substituted quinolines by AgOTf-catalyzed 2-aminobenzyl alcohol and alkyne/ketone or 2-aminophenethyl alcohol and aldehyde has been developed. The electronic properties of the substituents on the alkyne, ketone, and aldehyde were investigated. It was found that molecules with both electron-donating and -withdrawing substituents were perfectly suitable substrates for this transformation, and the expected products were obtained in moderate to excellent yields. Moreover, the use of inexpensive starting materials and environmentally benign oxidants makes this atom efficient method particularly attractive.
- Xu, Xuefeng,Zhang, Xu,Liu, Wenming,Zhao, Qiang,Wang, Zhiqiang,Yu, Lintao,Shi, Fu
-
supporting information
p. 3790 - 3792
(2015/06/08)
-
- Chiral phosphoric acid catalyzed oxidative kinetic resolution of cyclic secondary amine derivatives including tetrahydroquinolines by hydrogen transfer to imines
-
A chiral Bronsted acid catalyzed dehydrogenative kinetic resolution of tetrahydroquinoline derivatives, which are representative of cyclic secondary amines, based on their hydrogen transfer to aromatic imines was efficiently achieved with high enantioselectivities. This hydrogen transfer of tetrahydroquinolines to imines was not driven by their aromatization to quinolines. This dehydrogenative kinetic resolution could be also applied to the asymmetric synthesis of various benzofused heterocycles containing secondary amine cores.
- Saito, Kodai,Miyashita, Hiromitsu,Akiyama, Takahiko
-
supporting information
p. 16648 - 16651
(2015/11/25)
-
- Ferrocene-appended anionic N-heterocyclic carbene and its complex with silver(I): Synthesis, structure and catalytic evaluation
-
A binuclear Ag(I) complex (1) bridged by two anionic N-heterocyclic carbene (NHC) ligands ferrocenoyl(1-mesitylimidazol- 2-ylidine-3-yl)amide is synthesized. X-ray structure reveals a [Ag...Ag] core spanned by two ligands, each bridging two metals through carbene carbon and amido nitrogen. The neutral complex (1) is highly soluble in a variety of organic solvents and is thermally stable. Complex (1) efficiently catalyses aniline-mediated synthesis of substituted quinolines from 2-aminobenzaldehyde and terminal alkynes.
- Sarbajna, Abir,Sadhukhan, Nabanita,Saha, Sayantani,Bera, Jitendra K
-
p. 1072 - 1077
(2013/09/12)
-
- Design, synthesis, and structure-activity relationship study of conformationally constrained analogs of indole-3-carboxamides as novel CB1 cannabinoid receptor agonists
-
Novel tricyclic indole-3-carboxamides were synthesized as structurally restricted analogs of bicyclic indoles, and found to be potent CB1 cannabinoid receptor agonists. The CB1 agonist activity depended on the absolute configuration of the chiral center of the tricyclic ring. The preferred enantiomer was more potent than the structurally unconstrained lead compound. Structure-activity relationships in the amide side chain of the indole C-3 position were also investigated.
- Kiyoi, Takao,York, Mark,Francis, Stuart,Edwards, Darren,Walker, Glenn,Houghton, Andrea K.,Cottney, Jean E.,Baker, James,Adam, Julia M.
-
scheme or table
p. 4918 - 4921
(2010/11/04)
-
- A method for the synthesis of substituted quinolines via electrophilic cyclization of 1-azido-2-(2-propynyl)benzene
-
(Chemical Equation Presented) A new and efficient strategy for the synthesis of substituted quinolines via electrophilic cyclization is developed. The intramolecular cyclization of 1-azido-2-(2-propynyl)benzene 1 proceeds smoothly in the presence of electrophilic reagents (I2, Br 2 , ICl, NBS, NIS, and HNTf2) in CH3NO 2 at room temperature or in the presence of catalytic amounts of AuCl3/AgNTf2 in THF at 100 °C to afford the corresponding quinolines 2 in good to high yields. In the case of the electrophilic reagents, E of 2 is either I, Br, orH, depending on the reagent type, while E of 2 is H in the case of the electrophilic catalyst. 2010 American Chemical Society.
- Huo, Zhibao,Gridnev, Ilya D.,Yamamoto, Yoshinori
-
supporting information; experimental part
p. 1266 - 1270
(2010/04/29)
-
- Rh(I)-catalyzed alkylation of quinolines and pyridines via C-H bond activation
-
The scope of heterocycle ortho-alkylation has been dramatically expanded to include pharmaceutically important pyridines and quinolines, which contain only a single nitrogen. The reactions, which are conducted at a high concentration (0.8 M), can be performed with catalyst loadings as low as 1% Rh. Substitution ortho to the heterocycle ring nitrogen is required for efficient alkylation and is consistent with the intermediacy of a Rh-carbene intermediate similar to those proposed in our earlier work. Copyright
- Lewis, Jared C.,Bergman, Robert G.,Ellman, Jonathan A.
-
p. 5332 - 5333
(2008/02/04)
-
- Synthesis of substituted pyridines and quinolines
-
A variety of N-vinyl and N-aryl amides were converted to the corresponding pyridine and quinoline derivatives, respectively. Amide activation and nucleophilic addition of copper(I) (trimethylsilyl)acetylide efficiently provided the desired alkynyl imines. Ruthenium-catalyzed protodesilylation and cycloisomerization of these imines gave the corresponding azaheterocycles. Georg Thieme Verlag Stuttgart.
- Hill, Matthew D.,Movassaghi, Mohammad
-
p. 1115 - 1119
(2008/02/02)
-
- Synthesis of substituted pyridine derivatives via the ruthenium-catalyzed cycloisomerization of 3-azadienynes
-
We describe a two-step conversion of various N-vinyl and N-aryl amides to the corresponding substituted pyridines and quinolines, respectively. The process involves the direct conversion of amides, including sensitive N-vinyl amides, to the corresponding trimethylsilyl alkynyl imines followed by a ruthenium-catalyzed protodesilylation and cycloisomerization. A wide range of new alkynyl imines are prepared and readily converted to the corresponding azaheterocycles. Copyright
- Movassaghi, Mohammad,Hill, Matthew D.
-
p. 4592 - 4593
(2007/10/03)
-
- An unusual de-nitro reduction of 2-substituted-4-nitroquinolines
-
The treatment of a variety of 2-substituted-4-nitroquinolines with Sn in the presence of concentrated hydrochloric acid in ethanol at 70 °C for 2-4 h afforded unusual de-nitro products 2-substituted-quinolines in good yields.
- Zhou, Yu,Li, Jian,Liu, Hong,Zhao, Linxiang,Jiang, Hualiang
-
p. 8511 - 8514
(2007/10/03)
-
- TRICYCLIC 1-[(3-INDOL-3-YL)CARBONYL] PIPERAZINE DERIVATIVES AS CANNABINOID CB1 RECEPTOR AGONISTS
-
The invention relates to tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivative having the general Formula (I) wherein X is CH2, O or S; R represents 1-3 substituents independently selected from H, (C1-4)alkyl, (C1-4)alky
- -
-
-
- Mechanism of the Gif-Barton type alkane functionalization by halide and pseudohalide ions.
-
The functionalization of alkanes by halide ions under the conditions of a Gif system can be explained by free-radical redox processes.The evidence is provided by trapping the intermediate alkyl radical by protonated heteroaromatic bases.
- Minisci, Francesco,Fontana, Francesca
-
p. 1427 - 1430
(2007/10/02)
-
- A novel radical reaction of alkyl xantates useful for the selective substitution of heteroaromatic bases
-
Cyclohexyl radical is generated from cyclohexyldithiocarbonate and benzoyl peroxide. The radical source is used for the alkylation of heteroaromatic bases.
- Coppa, Fausta,Fontaria, Francesca,Minisci, Francesco,Pianese, Giuseppe,Tortoreto, Paola,Zhao, Lihua
-
p. 687 - 690
(2007/10/02)
-
- A NEW PHOTOCHEMICAL METHOD OF HOMOLYTIC ALKYLATION OF HETEROAROMATIC BASES BY ALKYL IODIDES AND IODOSOBENZENE DIACETATE
-
Photolysis of iodobenzene diacetate in the presence of alkyl iodides, protonated heteroaromatic bases and benzoic acid resulted in the selective alkylation of the α and γ positions on lepidine and quinoline.
- Fontana, Francesca,Minisci, Francesco,Barbosa, Maria Claudia Nogueira,Vismara, Elena
-
p. 167 - 168
(2007/10/02)
-
- Homolytic alkylation of heteroaromatic bases : The problem of monoalkylation
-
The silver-catalyzed decarboxylation of carboxylic acids by persulphate leads to alkyl radicals, which have been utilized for the selective alkylation of heteroaromatic bases. The method is particularly efficient in a water-chlorobenzene two-phase system for two reasons : it considerably increases the selectivity in monoalkylation when more positions of high nucleophilic reactivity (i.e. α and γ) are available in the heterocyclic ring (i.e. quinoline , 4-cyano- and 4-ethylpyridine, pyrazine , quinoxaline etc.) and it determines a much higher efficiency for the radical sources when the silver salt catalysis is deactivated by complexation of the salt with the heterocyclic compound . The high selectivity in monoalkylation has been obtained by the combination of polar effects and the increased lipophilicity of the alkylated product, which makes its extraction from the aqueous solution by the organic solvent easier.
- Fontana,Minisci,Barbosa, M. C. Nogueira,Vismara
-
p. 2525 - 2538
(2007/10/02)
-
- A NEW GENERAL METHOD OF HOMOLYTIC ALKYLATION OF PROTONATED HETEROAROMATIC BASES BY CARBOXYLIC ACIDS AND IODOSOBENZENE DIACETATE.
-
A new general, simple and mild procedure is reported in this communication, based on the photochemically induced decarboxylation of carboxylic acids by iodosobenzene diacetate to obtain the substitution of bases by nucleophilic alkyl radicals.
- Minisci, Francesco,Vismara, Elena,Fontana, Francesca,Barbosa, Maria Claudia Nogueira
-
p. 4569 - 4572
(2007/10/02)
-
- REACTIONS OF TRIALKYL(2- or 4-QUINOLYL)BORATES
-
Reactions of trialkyl(2-quinolyl)borates and trialkyl(4-quinolyl)borates were investigated.
- Ishikura, Minoru,Oda, Izumi,Kamada, Machiko,Terashima, Masanao
-
p. 959 - 968
(2007/10/02)
-
- Polar Effects in Free-Radical Reactions. Rate Constants in Phenylation and New Methods of Selective Alkylation of Heteroaromatic Bases
-
The rate constants for the addition of the phenyl radical to protonated and unprotonated 4-substituted pyridines have been determined by competition with chlorine abstraction from CCl4.The constants range from 2 * 105 to 6 * 106 M-1 s-1 depending on the substituent and on the degree of protonation.The phenyl radical shows a clear-cut nucleophilic character.On the basis of these rate constants, the use of phenyl radical from diazonium salt or benzoyl peroxide to generate alkyl radicals by iodine or hydrogen abstraction has been developed as a general procedure for the alkylation of heteroaromatic bases.This reaction is characterized by high yields and selectivities.
- Minisci, Francesco,Vismara, Elena,Fontana, Francesca,Morini, Giampiero,Serravalle, Marco,Giordano, Claudio
-
p. 4411 - 4416
(2007/10/02)
-