- Visible-light-mediated minisci C-H alkylation of heteroarenes with 4-alkyl-1,4-dihydropyridines using O2as an oxidant
-
Herein, we report a protocol for direct visible-light-mediated Minisci C-H alkylation reactions of N-heteroarenes with 4-alkyl-1,4-dihydropyridines at room temperature with molecular oxygen as an oxidant. The protocol permits efficient functionalization of various N-heteroarenes with a broad range of cyclic and acyclic primary, secondary, and tertiary alkyl groups and is scalable to the gram level. This mild protocol uses an inexpensive, green oxidant and is suitable for late-stage C-H alkylation of complex nitrogen-containing molecules. We demonstrated its utility by preparing or functionalizing several pharmaceuticals and natural products.
- Dong, Jianyang,Liu, Yuxiu,Song, Hongjian,Wang, Qingmin,Xu, Wentao,Yue, Fuyang
-
supporting information
p. 5599 - 5604
(2020/09/21)
-
- Catalytic Selective Metal-Free Cross-Coupling of Heteroaromatic N-Oxides with Organosilanes
-
A metal-free, regioselective C-H functionalization of heteroaromatic N-oxides has been developed. The method enables the synthesis of various benzylated and alkynylated N-heterocycles in a transition-metal-free manner employing organosilanes as coupling partners. The unanticipated reactivity has been exploited for the synthesis of a number of symmetrical disubstituted acetylenes from ethynyltrimethylsilane via carbon-silicon bond metathesis.
- Puthanveedu, Mahesh,Polychronidou, Vasiliki,Antonchick, Andrey P.
-
supporting information
p. 3407 - 3411
(2019/05/10)
-
- Direct Arylation of Unactivated Alkanes with Heteroarenes by Visible-Light Catalysis
-
The functionalization of aliphatic C-H bonds is both a major challenge and a desirable goal in organic synthesis. Here, we describe the successful arylation of unactivated alkanes with heteroarenes by using iridium polypyridyl complexes as the photocatalyst and persulfate as the HAT catalyst precursor under visible-light irradiation. This reaction features good functional group tolerance and broad scope with regard to both alkane and heteroarene substrates (37 examples), which allows direct access to alkyl-substituted N-heteroarenes, a key structural motif in natural products and bioactive molecules.
- Huang, Cheng,Wang, Jing-Hao,Qiao, Jia,Fan, Xiu-Wei,Chen, Bin,Tung, Chen-Ho,Wu, Li-Zhu
-
p. 12904 - 12912
(2019/09/09)
-
- Visible-light-induced C(sp3)-H oxidative arylation with heteroarenes
-
Considering the ubiquitous C(sp3)-H and the important value of alkylated heteroarenes, developing a universal method for C(sp3)-H arylation with heteroarenes is significant. Herein, we proposed a method where Selectfluor can promote
- Liang, Xing-An,Niu, Linbin,Wang, Shengchun,Liu, Jiamei,Lei, Aiwen
-
supporting information
p. 2441 - 2444
(2019/03/26)
-
- Radical Benzylation of Quinones via C-H Abstraction
-
Herein we report the development of radical benzylation reactions of quinones using Selectfluor and catalytic Ag(I) initiators. The reaction is believed to proceed via a C-H abstraction mechanism after Ag(I)-mediated reduction of Selectfluor. This reaction occurs under mild conditions and is effective for a variety of quinones and radical precursors bearing primary benzylic carbons. The use of preformed Ag(4-OMePy)2NO3 as a catalyst proved effective in improving the reaction efficiency by reducing unwanted degradation pathways available to Selectfluor.
- Galloway, Jordan D.,Mai, Duy N.,Baxter, Ryan D.
-
p. 12131 - 12137
(2019/10/02)
-
- Photocatalyzed ortho-Alkylation of Pyridine N-Oxides through Alkene Cleavage
-
A photocatalyzed reaction of pyridine N-oxides with alkenes gives ortho-alkylated pyridines with cleavage of the carbon–carbon double bond. Benzyl and secondary alkyl groups are incorporated at the ortho position of pyridines in one pot.
- Zhou, Wang,Miura, Tomoya,Murakami, Masahiro
-
supporting information
p. 5139 - 5142
(2018/05/30)
-
- Palladium-Catalyzed Arylation of Benzylic C-H Bonds of Azaarylmethanes with Aryl Sulfides
-
Benzylic C-H arylation of azaarylmethanes with aryl sulfides has been developed by using a Pd-NHC catalyst and an amide base. Various azaarylmethanes and aryl sulfides were involved in the reaction to afford the corresponding diarylmethanes in good to excellent yields. Moreover, triarylmethane synthesis was accomplished through iterative arylations of 2- or 4-methylpyridine with two different aryl sulfides.
- Gao, Ke,Yamamoto, Keita,Nogi, Keisuke,Yorimitsu, Hideki
-
supporting information
p. 2956 - 2960
(2017/10/06)
-
- A VERSATILE LIGAND FOR PALLADIUM-CATALYZED META-C-H FUNCTIONALIZATIONS
-
A class of mono-protected 3-amino-2- hydroxypyridine (MPAHP) ligands that enable the meta- C-H arylation of anilines, phenols, phenylacetic acids, and biologically relevant heterocyclic compounds using norbornene as a transient mediator is disclosed. The applicability of this meta-arylation methodology in the pharmaceutical industry is illustrated for heteroaryl substrates and heteroaryl iodide coupling partners, a feat made possible by using the MPAHP ligand. The enabling nature of MPAHP ligands to achieve other meta-C-H functionalization processes is also illustrated by the development of a meta-C-H amination reaction and a meta-C-H alkynylation reaction.
- -
-
Page/Page column 97; 98
(2017/11/15)
-
- Oxidant-Triggered C1-Benzylation of Isoquinoline by Iodine-Catalyzed Cross-Dehydrogenative-Coupling with Methylarenes
-
A practical iodine-catalyzed oxidative functionalization of isoquinolines with methylarenes is developed, which can be triggered by the selected oxidants to produce C1- or N-benzyl-substituted products selectively. This method utilizes readily available isoquinolines and methylarenes as starting materials and proceeds under metal-free conditions with broad substrate scope with respect to methylarenes, avoiding the usage of expensive metal catalysts and generation of halide and metal wastes.
- Shi, Xin,Zhang, Feng,Luo, Wen-Kun,Yang, Luo
-
supporting information
p. 494 - 498
(2017/02/24)
-
- Ruthenium-Mediated Dual Catalytic Reactions of Isoquinoline via C?H Activation and Dearomatization for Isoquinolone
-
We have unraveled the ruthenium-promoted prototype reaction based on C(sp2)?C(sp3) bond formation through the reigoselective C?H activation of isoquinoline and pyridine derivatives with various alkyl halides, leading to 1-substituted isoquinoline products in good yield. This C?H catalytic reaction did not rely on chelation assistance of the directing group of the substrates. The dimer [RuCl2(p-cymene)]2in combination with an N-heterocyclic carbene ligand, adamantanecarboxylic acid and K2CO3base in N-methyl-2-pyrrolidone solution at 150 °C are the best conditions. Simultaneously, we are also able to chemically tune the reaction mode to dearomatization by adding water, leading to isoquinolone products. This reaction methodology is not suitable for other nitrogen-containing heteroarenes such as pyridazines and pyrimidines. (Figure presented.).
- Wang, Ting-Hsuan,Lee, Wei-Chih,Ong, Tiow-Gan
-
supporting information
p. 2751 - 2758
(2016/09/13)
-
- Ligand-Promoted Meta-C-H Arylation of Anilines, Phenols, and Heterocycles
-
Here we report the development of a versatile 3-acetylamino-2-hydroxypyridine class of ligands that promote meta-C-H arylation of anilines, heterocyclic aromatic amines, phenols, and 2-benzyl heterocycles using norbornene as a transient mediator. More than 120 examples are presented, demonstrating this ligand scaffold enables a wide substrate and coupling partner scope. Meta-C-H arylation with heterocyclic aryl iodides as coupling partners is also realized for the first time using this ligand. The utility for this transformation for drug discovery is showcased by allowing the meta-C-H arylation of a lenalidomide derivative. The first steps toward a silver-free protocol for this reaction are also demonstrated.
- Wang, Peng,Farmer, Marcus E.,Huo, Xing,Jain, Pankaj,Shen, Peng-Xiang,Ishoey, Mette,Bradner, James E.,Wisniewski, Steven R.,Eastgate, Martin D.,Yu, Jin-Quan
-
supporting information
p. 9269 - 9276
(2016/08/05)
-
- Rh-catalyzed sequential oxidative C-H activation/annulation with geminal-substituted vinyl acetates to access isoquinolines
-
The concise synthesis of 3-substituted or non-C3-substituted isoquinolines through Rh-catalyzed sequential oxidative C-H activation/annulation with geminal-substituted vinyl acetates was developed with good functional group tolerance. The protocol was successfully applied to the total synthesis of the natural product papaverine.
- Chu, Haoke,Sun, Song,Yu, Jin-Tao,Cheng, Jiang
-
supporting information
p. 13327 - 13329
(2015/08/24)
-
- C1-Benzyl and benzoyl isoquinoline synthesis through direct oxidative cross-dehydrogenative coupling with methyl arenes
-
An oxidative cross-dehydrogenative coupling (CDC) of isoquinolines with methyl arenes has been developed, allowing for the facile synthesis of a broad range of structurally diverse C1-benzyl and -benzoyl isoquinolines. The direct use of readily available methyl arenes as coupling partners avoids unproductive steps for preactivating the functional group installation, and is therefore attractive. The method exhibits excellent chemoselectivity, affording exclusive benzylated products in the presence of DTBP and a catalytic amount of Y(OTf)3, and yielding benzoylated ones with TBHP and a catalytic amount of MnO2.
- Wan, Miao,Lou, Hongxiang,Liu, Lei
-
supporting information
p. 13953 - 13956
(2015/09/07)
-
- Metal-Free Oxidative Decarbonylative Coupling of Aliphatic Aldehydes with Azaarenes: Successful Minisci-Type Alkylation of Various Heterocycles
-
A metal-free oxidative decarbonylative coupling of aliphatic aldehydes with various electron-deficient heterocycles has been developed. This reaction is supposed to be realized via a Minisci-type mechanism, based on the substrate scope, regioselectivity and radical trapping experiments. The ready availability of aliphatic aldehydes, metal-free conditions and broad substrate scope should make this method attractive for the late-stage alkylation of bioactive heterocycles.
- Tang, Ren-Jin,Kang, Lei,Yang, Luo
-
supporting information
p. 2055 - 2060
(2015/06/23)
-
- Regioselective photochemical C-OMe bond formation initiated by one-electron transfer and N-OMe bond fragmentation in electron donor-acceptor systems
-
Compounds that integrate electron donor-acceptor subunits with N-methoxyisoquinolinium as acceptors and substituted (methoxy)benzenes as donors were synthesized and their luminescent and photochemical properties studied. Photolysis yielded the corresponding photomethoxylation products in a two-step process that involves N-OMe bond scission followed by C-OMe bond formation. Homolysis of the N-OMe bond restores the aromatic isoquinoline nucleus and produces a methoxy radical that can couple to the required ring carbon atom in the benzene cation radical to give the products in a regioselective process controlled by the spin density of the cation radical. This photoprocess involves two different pathways: methoxylation of the acceptor (intracomponent methoxylation) or the donor (intercomponent metoxylation). Both methoxy-transfer pathways are controlled by the donoating ability (redox potential) of the donor subunit, consistent with the emission observed upon excitation of the charge-transfer state in systems that undergo intermethoxylation.
- Collado, Daniel,Perez-Inestrosa, Ezequiel
-
p. 1800 - 1808
(2012/05/04)
-
- Organocatalytic asymmetric destruction of 1-benzylated Reissert compounds catalysed by quaternary cinchona alkaloids
-
The enantiomeric enrichment of racemic 1-benzylated Reissert compounds under organocatalytic biphasic conditions is presented. The enrichment is the consequence of an asymmetric destruction of the racemic compounds resulting in the formation of the corres
- Frisch, Kim,Jorgensen, Karl Anker
-
p. 2966 - 2974
(2008/03/14)
-
- Covalently linked acceptor - Donor systems based on isoquinoline N-oxide acceptor: Photoinduced electron transfer produces dual-channel luminescent systems that evolve chemically to photohydroxylation of the aromatic donor
-
Acceptor-donor compounds containing the isoquinoline N-oxide acceptor and (methoxy)nbenzene (n = 0, 1, 2, 3) electron donors were studied. The two chromophores are connected by a CH2 bridging unit. All acceptor-donor compounds exhibi
- Collado, Daniel,Perez-Inestrosa, Ezequiel,Suau, Rafael
-
p. 3574 - 3584
(2007/10/03)
-
- Coralyne analogs as topoisomerase inhibitors
-
The present invention provides protoberberine alkaloid derivatives useful as anticancer agents, and methods of use thereof. The invention also provides protoberberine derivatives useful as topoisomerase inhibitors. The invention further provides coralyne and nitidine derivatives which are topoisomerase I-targeted therapeutics effective against camptothecin resistant cancer cells, and are especially effective against CNS tumors.
- -
-
-
- Thermal rearrangement of aromatic acetal and thioacetal derivatives
-
Thermolysis of benzaldehyde dibenzyl acetal 1 by refluxing at 250°C for 3 days give H2O, toluene, benzaldehyde, benzyl alcohol, bibenzyl, stilbene and benzylphenylcarbinol. Similar treatment of cinnamaldehyde diphenyl thio-acetal 2 furnishes H2S, bibenzyl, toluene, stilbene, thiophenol, diphenyl sulfide, indene, thianthrene, 2,3,4,5-tetraphenylthiophene and polystyrene. Moreover thermolysis of 1 in the presence of isoquinoline gives 1-benzylisoquinoline in addition to the previous products. From these results a free radical mechanism has been postulated to take place through the initial homolysis of different bonds in the acetal molecules.
- Gaber,Aly
-
p. 657 - 661
(2007/10/03)
-
- Isoxazolinoisoquinoline Heterocycles via Solid-Phase Reinsert and Suzuki Reactions
-
A traceless solid-phase synthesis strategy has been developed that delivers novel isoxazolinoisoquinoline heterocycles. The process consists of solid-phase Reissert formation (isoquinoline → I), Suzuki coupling lithiation, and subsequent C1-alkylation (I → II), and exo-olefin selective 1,3-dipolar nitrile oxide cycloaddition followed by Reissert hydrolysis (II → III) to liberate the targeted heterocycle.
- Lorsbach, Beth A.,Bagdanoff, Jeffrey T.,Bryan Miller,Kurth, Mark J.
-
p. 2244 - 2250
(2007/10/03)
-
- INDOLOPYRIDINES WITH A HETERO ATOM AT A POSITION OF FUSION. 5. CATALYTIC SYNTHESIS OF INDOLOISOQUINOLINE BY PYROLYSIS OF BENZYLISOQUINOLINES
-
High-temperature heterocyclization of α-benzylisoquinolines on oxide-type catalysts gave angular indoloisoquinoline.
- Soldatova, S.A.,Alarcon, J. A. Rodriguez,Soldatenkov, A. T.
-
-
- The Reaction of N-Carboalkoxy Reissert Analogs with Carboxylic Acids
-
The reaction of N-carboalkoxy Reissert analogs in the presence of carboxylic acids yields the corresponding ester and heterocyclic base.Use of methoxy substituted benzoic acids yields, instead of the ester, the respective anhydride.Amides can also be prepared in a similar fashion.
- Popp, Frank D.,Duarte, Frederick F.,Uff, Barrie C.
-
p. 1353 - 1355
(2007/10/02)
-
- Synthesis of 1-substituted isoquinolines
-
A method for the synthesis of particular isoquinoline compounds which are useful intermediates in the preparation of members of the family of opium alkaloids, such as morphine and codeine. Steps in the process include the acylation of the isoquinoline nitrogen; reaction of the acylated isoquinoline with a phosphorous compound; and condensation with a benzaldehyde derivative to yield a 1-benzyl isoquinoline.
- -
-
-
- Reaction of N-(p-Tolylsulfonyl)diphenylcyclopropenimine with Pyridinium and Isoquinolinium Ylides
-
N-(p-Tolylsulfonyl)diphenylcyclopropenimine (2) reacted smoothly with pyridinium N-carbethoxyamide (3) to afford a new ylide (5), in addition to stilbene 4, uracil 6, and pyrimidone 7.An observed thermal transformation of 5 to 6 and 7 is discussed.Reaction of the cyanocarboethoxy methylides 15a-c with 2 produced the internal salts 16a-c, while the dicarbethoxy, monocarbethoxy, and benzoyl methylides 15d-f gave the pyridine-free cyclics 26, 28, and 29, respectively.The isoquinolinium methylides 31a-c reacted in an analogous fashion, while the N-amides 33a,b afforded cycloadducts 34a,b.A series of reactions used to correlate the structures of the latter is described, including an observed cycloaddition mode for diphenylcyclopropenone (1) with 33a-c which yielded 39, 37, and 42, respectively.
- Pilli, Ronaldo Aloise,Rodrigues, J. Augusto,Kascheres, Albert
-
p. 1084 - 1091
(2007/10/02)
-
- NICKEL-PHOSPHINE COMPLEX-CATALYZED GRIGNARD COUPLING-II; GRIGNARD COUPLING OF HETEROCYCLIC COMPOUNDS
-
A general, versatile method for alkylation and arylation of haloheterocyclic compounds is reported.In the presence of a catalytic quantity of , where dppp stands for Ph2P(CH2)3PPh2, bromothiophenes, halopyridines, haloquinoline, and haloisoquinolines reacted with alkyl and aryl Grignard reagents at room temperature or at ether refluxing temperature to give the cross-coupling products.The coupling reactions has been applied to the synthesis of isoquinoline alkaloids.Reactivities of 2-thienyl and 2-pyridyl Grignard reagents have also been examined.
- Tamao, K.,Kodama, S.,Nakajima, I.,Kumada, M.,Minato, A.,Suzuki, K.
-
p. 3347 - 3354
(2007/10/02)
-
- Molecular Rearrangements: Part I - Pyrolysis of Dibenzyl Sulphide
-
Thermal rearrangement of dibenzyl sulphide in the absence of promoters has been thoroughly investigated and found to involve cleavage of the C-S bonds followed by a series of hydrogen abstraction, coupling, dehydrogenation and cyclisation reactions.The products isolated include H2S, toluene, benzaldehyde, dibenzyl, stilbene and tetraphenylthiophene.Benzylation products are also isolated when thermolysis is carried out in aromatic solvents such as β-naphthol and isoquinoline.A suitable mechanism has been suggested to account for the obtained products.It is noteworthy that no isomer redistribution precedes the coupling reactions.
- Abdel-Wahab, Aboel-Magd A.,Abdel-Rahman, Abdu E.
-
p. 636 - 639
(2007/10/02)
-
- Versatile and Efficient Synthesis of Aryl-1,2,3,4-tetrahydroisoquinolines: Nickel(II) Phosphine Ligand Catalyzed Coupling of Arylmagnesium Halides to Haloisoquinolines
-
Dichloronickel(II) (dppp) was used as catalyst to prepare some previously unreported arylisoquinolines 3, which were in turn hydrogenated to aryl-1,2,3,4-tetrahydroisoquinolines 2.This procedure is the most direct and ef
- Pridgen, Lendon N.
-
p. 1289 - 1291
(2007/10/02)
-
- Neuromuscular blocking agents
-
Short acting reversible neuromuscular blocking agents of the formula (I) STR1 where B and C is preferably meta or maybe para STR2 where m is 2, 3 or 4 and is preferably 2, R1, R2, R3, R4, R5, R6 and R7 are the same or different and are hydrogen or lower alkoxy of 1 to 4 carbon atoms Y is lower alkyl of 1 to 4 carbon atoms n is 2, 3 or 4, most preferably 3, provided that at least one of R1 to R4 and one of R5 to R7 is lower alkoxy and X is a pharmaceutically acceptable anion. These neuromuscular blocking agents of formula I are useful upon administration to a patient in providing muscular relaxation in the patient during surgery and are normally intravenously administered in a pharmaceutically acceptable carrier.
- -
-
-