5460-08-2Relevant articles and documents
Regioselective Arene C?H Alkylation Enabled by Organic Photoredox Catalysis
Holmberg-Douglas, Natalie,Onuska, Nicholas P. R.,Nicewicz, David A.
, p. 7425 - 7429 (2020/03/23)
Expanding the toolbox of C?H functionalization reactions applicable to the late-stage modification of complex molecules is of interest in medicinal chemistry, wherein the preparation of structural variants of known pharmacophores is a key strategy for drug development. One manifold for the functionalization of aromatic molecules utilizes diazo compounds and a transition-metal catalyst to generate a metallocarbene species, which is capable of direct insertion into an aromatic C?H bond. However, these high-energy intermediates can often require directing groups or a large excess of substrate to achieve efficient and selective reactivity. Herein, we report that arene cation radicals generated by organic photoredox catalysis engage in formal C?H functionalization reactions with diazoacetate derivatives, furnishing sp2–sp3 coupled products with moderate-to-good regioselectivity. In contrast to previous methods utilizing metallocarbene intermediates, this transformation does not proceed via a carbene intermediate, nor does it require the presence of a transition-metal catalyst.
N-Heterocyclic Carbenes as Key Intermediates in the Synthesis of Fused, Mesoionic, Tricyclic Heterocycles
Benaissa, Idir,Pallova, Lenka,Morantin, Marie-Emilie,Lafitte, Thomas,Huynh, Mathieu,Barthes, Cécile,Vendier, Laure,Lugan, No?l,Bastin, Stéphanie,César, Vincent
supporting information, p. 13030 - 13036 (2019/11/05)
Coupling between 5-bromoimidazo[1,5-a]pyridinium salts and malonate or arylacetate esters leads to a facile and straightforward access to the new mesoionic, fused, tricyclic system of imidazo[2,1,5-cd]indolizinium-3-olate. Mechanistic studies show that the reaction pathway consists of nucleophilic aromatic substitution on the cationic, bicyclic heterocycle by an enolate-type moiety and in the nucleophilic attack of a transient free N-heterocyclic carbene (NHC) species on the ester group; the relative order of these two steps depends on the nature of the starting ester. This work highlights the valuable implementation of free NHC species as key intermediates in synthetic chemistry, beyond their classical use as stabilizing ligands or organocatalysts.
Mechanism of the Selective Fe-Catalyzed Arene Carbon-Hydrogen Bond Functionalization
Postils, Verònica,Rodríguez, Mònica,Sabenya, Gerard,Conde, Ana,Díaz-Requejo, M. Mar,Pérez, Pedro J.,Costas, Miquel,Solà, Miquel,Luis, Josep M.
, p. 4313 - 4322 (2018/05/22)
The complete chemoselective functionalization of aromatic C(sp2)-H bonds of benzene and alkyl benzenes by carbene insertion from ethyl diazoacetate was unknown until the recent discovery of an iron-based catalytic system toward such transformation. A Fe(II) complex bearing the pytacn ligand (pytacn = L1 = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane) transferred the CHCO2Et unit exclusively to the C(sp2)-H bond. The cycloheptatriene compound commonly observed through Buchner reaction or, when employing alkyl benzenes, the corresponding derivatives from C(sp3)-H functionalization are not formed. We herein present a combined experimental and computational mechanistic study to explain this exceptional selectivity. Our computational study reveals that the key step is the formation of an enol-like substrate, which is the precursor of the final insertion products. Experimental evidences based on substrate probes and isotopic labeling experiments in favor of this mechanistic interpretation are provided.
Iron and manganese catalysts for the selective functionalization of arene C(sp2)-H bonds by carbene insertion
Conde, Ana,Sabenya, Gerard,Rodríguez, Mònica,Postils, Verònica,Luis, Josep M.,Díaz-Requejo, M. Mar,Costas, Miquel,Pérez, Pedro J.
supporting information, p. 6530 - 6534 (2016/06/01)
The first examples of the direct functionalization of non-activated aryl sp2 C-H bonds with ethyl diazoacetate (N2CHCO2Et) catalyzed by Mn- or Fe-based complexes in a completely selective manner are reported, with no formation of the frequently observed cycloheptatriene derivatives through competing Buchner reaction. The best catalysts are FeII or MnII complexes bearing the tetradentate pytacn ligand (pytacn= 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane). When using alkylbenzenes, the alkylic C(sp3)-H bonds of the substituents remained unmodified, thus the reaction being also selective toward functionalization of sp2 C-H bonds. Exclusive catalysis: Iron- and-manganese-based catalysts selectively functionalize the C(sp2)-H bonds of benzene or alkylbenzenes through the formal insertion of the CHCO2Et group from N2CHCO2Et (see scheme). When using alkylbenzenes, the alkylic C(sp3)-H bonds of the substituents remain unmodified.
PROCESS FOR PREPARING ARYL- AND HETEROARYLACETIC ACID DERIVATIVES
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Paragraph 0091-0094, (2014/06/23)
The invention relates to a process for preparing aryl- and heteroarylacetic acids and derivatives thereof by reaction of aryl or heteroaryl halides with malonic diesters in the presence of a palladium catalyst, of one or more bases and optionally of a phase transfer catalyst. This process enables the preparation of a multitude of functionalized aryl- and heteroarylacetic acids and derivatives thereof, especially also the preparation of arylacetic acids with sterically demanding substituents.
Process for Preparing Aryl- and Heteroarylacetic Acid Derivatives
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Page/Page column 5, (2011/08/06)
The present invention relates to a novel process for preparing α-arylmethylcarbonyl compound of the formula (III), characterized in that aryl- and heteroarylacetic acids and derivatives thereof of the formula (I) are reacted with α-halomethylcarbonyl compounds of the formula (II) in the presence of a palladium catalyst, of a phosphine ligand, of an inorganic base and of a phase transfer catalyst, optionally using an organic solvent.
Palladium-catalyzed cross-coupling of sterically demanding boronic acids with α-bromocarbonyl compounds
Zimmermann, Bettina,Dzik, Wojciech I.,Himmler, Thomas,Goossen, Lukas J.
experimental part, p. 8107 - 8112 (2011/11/07)
A catalyst system generated in situ from Pd(dba)2 and tri(o-tolyl)phosphine mediates the coupling of arylboronic acids with alkyl α-bromoacetates under formation of arylacetic acid esters at unprecedented low loadings. The new protocol, which involves potassium fluoride as the base and catalytic amounts of benzyltriethylammonium bromideas a phase transfer catalyst, is uniquely effective for the synthesis of sterically demanding arylacetic acid derivatives. (Figure presented)
Practical synthesis of 2-arylacetic acid esters via palladium-catalyzed dealkoxycarbonylative coupling of malonates with aryl halides
Song, Bingrui,Rudolphi, Felix,Himmler, Thomas,Goossen, Lukas J.
supporting information; experimental part, p. 1565 - 1574 (2011/08/03)
A new palladium-based system was developed that catalyzes the coupling of aryl halides with diethyl malonates in the presence of mild bases. In the course of the reaction, the intermediately formed diethyl arylmalonate is directly converted into the arylacetic acid ester via liberation of carbon dioxide and an alkanol. This cross-coupling/dealkoxycarbonylation process provides an efficient and high-yielding synthetic entry to diversely functionalized arylacetic acid esters. Two complementary protocols were developed, one of which is optimal for electron-rich, the other for electron-poor aryl halides. Both make use of low loadings of palladium(0) bis(dibenzylideneacetone) (0.5 mol%)/tri-tert-butylphosphonium tetrafluoroborate (1.1 mol%) as the catalyst and diethyl malonate as the reaction solvent. The new procedures are particularly effective for sterically hindered substrates. Copyright
Synthesis of arylacetic acid derivatives from diethyl malonate using in situ formed palladium(1,3-dialkylimidazolidin-2-ylidene) catalysts
?zdemir, Ismail,Yigit, Murat,?etinkaya, Engin,?etinkaya, Bekir
, p. 5823 - 5825 (2007/10/03)
The in situ prepared three component system Pd(OAc)2/1,3- bis(alkyl) imidazolinium halide LHX (1-5)/Cs2CO3 catalyses the arylation of diethyl malonate efficiently with accompanying dealkoxycarbonylation. Imidazolinium salts with bulky benzyl and alkoxyethyl groups were found to be the most efficient and afforded α-arylacetates in high yields when employing a wide variety of substrates.
1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof
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, (2008/06/13)
The invention relates to combinatorial libraries containing two or more novel piperidine-3-carboxamide derivative compounds, methods of preparing the piperidine-3-carboxamide derivative compounds and piperidine-3-carboxamide derivative compounds bound to a resin
