- Radical C?H Acylation of Nitrogen Heterocycles Induced by an Aerobic Oxidation of Aldehydes
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An aerobic radical approach for the synthesis of unsymmetrical heteroaryl ketones is described herein. The reaction involves cross-dehydrogenative coupling between aldehydes and heteroaromatic bases with molecular oxygen (O2). The key aspect of the method is the generation of reactive acyl radical via homolytic activation of aldehyde C?H bond using O2 as the sole oxidant. The reaction has a good substrate scope with respect to aldehydes and functionalized nitrogen heterocycles. Based on our mechanistic studies, a radical chain pathway is suggested for the reaction. A synthetic application of the method is demonstrated in the formal synthesis of natural alkaloid (±) angustureine.
- Paul, Subhasis,Bhakat, Manotosh,Guin, Joyram
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supporting information
p. 3154 - 3160
(2019/08/30)
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- Selective functionalization of methane, ethane, and higher alkanes by cerium photocatalysis
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With the recent soaring production of natural gas, the use of methane and other light hydrocarbon feedstocks as starting materials in synthetic transformations is becoming increasingly economically attractive, although it remains chemically challenging. W
- Hu, Anhua,Guo, Jing-Jing,Pan, Hui,Zuo, Zhiwei
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p. 668 - 672
(2018/09/26)
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- Alcohols as alkylating agents in heteroarene C-H functionalization
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Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One of the core principles underlying DNA biosynthesis is the radical-mediated elimination of H2O to deoxygenate ribonucleotides, an example of 'spin-centre shift', during which an alcohol C-O bond is cleaved, resulting in a carbon-centred radical intermediate. Although spin-centre shift is a well-understood biochemical process, it is underused by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors. Because conventional radical-based alkylation methods require the use of stoichiometric oxidants, increased temperatures or peroxides, a mild protocol using simple and abundant alkylating agents would have considerable use in the synthesis of diversely functionalized pharmacophores. Here we describe the development of a dual catalytic alkylation of heteroarenes, using alcohols as mild alkylating reagents. This method represents the first, to our knowledge, broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis. The value of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone.
- Jin, Jian,MacMillan, David W. C.
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- Rh-catalyzed sequential oxidative C-H activation/annulation with geminal-substituted vinyl acetates to access isoquinolines
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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
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supporting information
p. 13327 - 13329
(2015/08/24)
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- Dioxygen-Mediated Decarbonylative C-H Alkylation of Heteroaromatic Bases with Aldehydes
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An operationally simple and economical method for the direct alkylation of heteroaromatic bases employing readily available aldehydes as alkyl radical precursors and molecular oxygen as a reagent is presented. This simple transformation demonstrates a broad substrate scope with respect to aldehydes and nitrogen heterocycles, enabling the introduction of several medicinally important yet challenging alkyl moieties, such as ethyl, isopropyl, tert-butyl, and cyclohexyl to the different classes of heterocyclic bases in good to excellent yields. A simple method for the direct alkylation of heteroaromatic bases with aldehydes as inexpensive alkyl radical precursors and molecular oxygen as a reagent is presented. This transformation demonstrates a broad substrate scope with respect to aldehydes and nitrogen heterocycles, enabling the introduction of various alkyl moieties to heterocyclic bases (>40 examples) in good to excellent yields.
- Paul, Subhasis,Guin, Joyram
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supporting information
p. 17618 - 17622
(2015/12/05)
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- Trimethyl borate/magnesium halide complex-induced one-pot homologation reactions of isoquinoline with dialkyl-TMP-zincate
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Novel one-pot homologation reactions of isoquinoline with lithium dialkyl-TMP-zincate?2MgBrCl/trimethyl borate are described. 1-Alkylisoquinolines (2, 3A, 4A, 5A, 6, and 7) and 1-alkyl-3,4- dihydroisoquinolines (3B, 4B, and 5B) are easily prepared under t
- Seo, Hye Ji,Namgoong, Sung Keon
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scheme or table
p. 3594 - 3598
(2012/09/08)
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- Isoxazolinoisoquinoline Heterocycles via Solid-Phase Reinsert and Suzuki Reactions
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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.
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p. 2244 - 2250
(2007/10/03)
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- Reissert Compound Studies. LXV. Praparation of Reissert Compounds Derived from α,β-Unsaturated Acid Chlorides
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Reissert compounds derived from α,β-unsaturated acid chlorides were prepared.The conjugate base obtained from these Reissert compounds exhibited the following carbanion reactions: 1) Alkylation, 2) Condensation with benzaldehyde, 3) Rearrangement to give dimeric compounds rather than simple rearranged compounds.In the case of alkylated isoquinoline Reissert compounds, the attempted rearrangement led to ring annellated amines.
- Hahn, Jung-Tai,Kant, Joydeep,Popp, Frank D.,Chhabra, Siri Ram,Uff, Barrie C.
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p. 1165 - 1176
(2007/10/02)
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- The Reaction of N-Carboalkoxy Reissert Analogs with Carboxylic Acids
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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.
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p. 1353 - 1355
(2007/10/02)
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- Polar Effects in Free-Radical Reactions. Rate Constants in Phenylation and New Methods of Selective Alkylation of Heteroaromatic Bases
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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
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p. 4411 - 4416
(2007/10/02)
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- Nucleophilic Displacement of Primary Amino Groups via 1-Substituted 4-Tosylimidazoles
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Two methods are discribed for the replacement of primary amino groups, situated either α or γ to a heterocyclic nitrogen atom, by ethoxy, alkylthio, and arylthio substituents, by Wittig reagents, and by hydrogen.Both methods involve transformation of the primary amino group into a nucleofugic pendant heterocycle.The first converts the primary amino group into a 5-phenyl-1-tetrazolyl substituent by benzoylation, formation of the imidoyl chloride, and reaction with sodium azide, while the second converts the primary amino group into a 1-(4-tosylimidazolyl) substituent by reaction with triethyl orthoformate and acid to give the (ethoxymethylene)amino derivative, which is then condensed with tosylmethyl isocyanide (TosMIC) anion.The 1-(4-tosylimidazolyl) substituent is shown to be more susceptible to nucleophilic displacement by a wider range of nucleophiles.
- Taylor, Edward C.,LaMattina, John L.,Tseng, Chi-Ping
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p. 2043 - 2047
(2007/10/02)
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- NICKEL-PHOSPHINE COMPLEX-CATALYZED GRIGNARD COUPLING-II; GRIGNARD COUPLING OF HETEROCYCLIC COMPOUNDS
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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.
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p. 3347 - 3354
(2007/10/02)
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- A ONE-POT ISOQUINOLINE SYNTHESIS BY CYCLODEHYDROGENATION OF BENZYLAMINOACETALS WITH CHLOROSULFONIC ACID
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A direct preparation of the fully aromatized isoquinolines (3a-l) by the cyclodehydrogenation of benzylamnoacetals (2a-l) with chlorosulfonic acid is described.Comparing the behavior of chlorosulfonic acid with that of sulfuric acid toward 1,2-dihydroisoquinoline, it is able to be suggested that benzylaminoacetals were cyclized first to 1,2-dihydroisoquinolines, subsequently, dehydrogenated to the fully aromatized isoquinolines by the hydride abstraction with ClSO3H.Subtitution by a larger R3 group than isopropyl in the acetal ArCH(R3)NHCH2CH(OEt)2, interfered this second step, so the corresponding isoquinolines could not be obtained.
- Kido, Kazuko,Watanabe, Yasuo
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p. 1151 - 1154
(2007/10/02)
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