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Carboxylic acid

About: Carboxylic acid is a research topic. Over the lifetime, 48544 publications have been published within this topic receiving 605696 citations.


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TL;DR: In this paper, the authors analyzed time-series aerosol samples collected in Tokyo every 3-h during summer and winter campaigns for homologous dicarboxylic acids (C 2 -C 10 ), ketocarboxyl acid(C 2 −C 4 ), and α -dicarbonyls (C2 -C 3 ) using a GC and GC/MS.

315 citations

Journal ArticleDOI
TL;DR: Kinetic data for the C-H bond activation of 2-phenylpyridine by Ru(II)(carboxylate)(2)(p-cymene) I (acetate) and I' (pivalate) are available for the first time and reveal an irreversible autocatalytic process catalyzed by the coproduct HOAc or HOPiv.
Abstract: Kinetic data for the C-H bond activation of 2-phenylpyridine by Ru(II)(carboxylate)(2)(p-cymene) I (acetate) and I' (pivalate) are available for the first time. They reveal an irreversible autocatalytic process catalyzed by the coproduct HOAc or HOPiv (acetonitrile, 27 °C). The overall reaction is indeed accelerated by the carboxylic acid coproduct and water. It is retarded by a base, in agreement with an autocatalytic process induced by HOAc or HOPiv that favors the dissociation of one carboxylate ligand from I and I' and consequently the ensuing complexation of 2-phenylpyridine (2-PhPy). The C-H bond activation initially delivers Ru(O(2)CR)(o-C(6)H(4)-Py)(p-cymene) A or A', containing one carboxylate ligand (OAc or OPiv, respectively). The overall reaction is accelerated by added acetates. Consequently, C-H bond activation (faster for acetate I than for pivalate I') proceeds via an intermolecular deprotonation of the C-H bond of the ligated 2-PhPy by the acetate or pivalate anion released from I or I', respectively. The 18e complexes A and A' easily dissociate, by displacement of the carboxylate by the solvent (also favored by the carboxylic acid), to give the same cationic complex B(+) {[Ru(o-C(6)H(4)-Py)(p-cymene)(MeCN)](+)}. Complex B(+) is reactive toward oxidative addition of phenyl iodide, leading to the diphenylated 2-pyridylbenzene.

313 citations

Journal ArticleDOI
TL;DR: A method of palladium-catalyzed synthesis of protected unnatural amino acids by C-H bond functionalization that employs readily available starting materials derived from chiral pool is reported.
Abstract: During the last years, transition-metal-catalyzed carbon-hydrogen bond functionalization has witnessed an explosive growth.[1] The use of C-H bond as a functional group is appealing because of shortening of reaction pathways and simplification of retrosynthetic analyses. However, most of the reports that deal with carbon-hydrogen bond conversion to carbon-carbon bonds involve either methodology development or mechanistic investigations. The applications in synthesis of natural products or their analogues are rare.[2] The limited use may be explained by the following issues. First, methods that result in functionalization of alkane C-H bonds are relatively rare.[3] Second, harsh reaction conditions are typically used that may be incompatible with sensitive functionalities. Third, methods often lack generality and require non-removable directing groups. We have reported the β-arylation of carboxylic acid and γ-arylation of amine derivatives by employing an 8-aminoquinoline or picolinic acid auxiliary, catalytic Pd(OAc)2, and an aryl iodide coupling partner (Scheme 1).[4a] Subsequently, several other auxiliaries were investigated for carboxylic acid β-arylation.[4b] Use of 2-thiomethylaniline auxiliary affords selective monoarylation of methyl groups. In contrast, use of 8-aminoquinoline auxiliary allows either diarylation of methyl or monoarylation of methylene groups. The arylation regioselectivity is determined by formation of double five-membered chelate 1. Scheme 1 Auxiliaries for C-H Bond Arylation Several other groups have recently used these directing groups in synthesis of natural products.[5] Corey has used the 8-aminoquinoline auxiliary to arylate sp3 C-H bonds in amino acid derivatives.[5a] However, monoarylation of alanine derivatives was not demonstrated and stereochemical integrity of arylation products as well as directing group removal was not reported. Developing new methodology for unnatural amino acid synthesis is important since they are used in drug discovery, protein engineering, peptidomimetics, glycopeptide synthesis, and click chemistry in biologically relevant systems.[6–7] Methods for preparation of chiral nonracemic unnatural α-amino acids involve synthesis of racemates followed by resolution, use of chiral auxiliaries, asymmetric hydrogenation, and biological approaches.[8] A general method for unnatural amino acid synthesis from chiral pool would expand the toolbox that is available for their preparation. We report here a method of palladium-catalyzed synthesis of protected unnatural amino acids by C-H bond functionalization that employs readily available starting materials derived from chiral pool. The functionalizaton of amino acid C-H bonds requires installation of a directing group and protection of the amino group. Phthaloyl group was chosen for protection of the amino functionality.[9] Directing group was installed by reacting phthaloylamino acid chlorides[10] with 8-aminoquinoline or 2-thiomethylaniline. N-Phthaloylalanine derivative 2 was arylated by PhI in the presence of a palladium catalyst and base. Subsequently, directing group was removed by treatment with BF3*Et2O in methanol at 100 °C (Table 1).[11] Nearly identical enantiomeric excess of 4 was observed by employing AgOAc, AgOCOCF3, or CsOAc bases at 60–70 °C (entries 3–8). Higher reaction temperatures resulted in erosion of product enantiomeric excess (entries 1, 4, 9), as did addition of pivalic acid (entry 2). The optimal combination of yield and enantiomeric excess was obtained by employing palladium acetate catalyst in combination with AgOAc at 60 °C (entry 5). Table 1 Reaction Optimization. Use of 2-thiomethylaniline derivative allows for a selective monoarylation of methyl group in 2 (Scheme 2). Arylation of 2 by iodobenzene affords 3 in 78% yield. 4-Methoxyiodobenzene is reactive and the arylation product 5 was isolated in 68% yield. 2-Iodonaphthalene and 2-iodobenzothiophene afforded the products in good yields. β-(2-Naphthyl)alanine-containing peptides are highly specific Pin1 inhibitors.[12] Interestingly, 3-iodo-1-methylindole can be coupled with 2 to give an N-methylated tryptophan derivative 8 in 61% yield. An azido functionality is tolerated and 3-azidophenylalanine derivative 9 was obtained in 81% yield. Thus, a wide variety of substituted phenylalanines can be made from a readily available, single starting material 2 in a convergent fashion. Two of the arylated derivatives were subjected to cleavage of directing group. N-Phthaloylphenylalanine methyl ester 4 was obtained in 87% yield and 90% ee. The benzothiophene derivative 10 was obtained in 80% yield. Scheme 2 Synthesis of Modified Phenylalanine Derivatives. 8-Aminoquinoline directing group can be used for diarylation of methyl and monoarylation of methylene functionalities (Scheme 3). Diarylation of 11 was accomplished by 3,4-dimethyl-1-iodobenzene and 4-iodobenzoic acid ethyl ester and the products 12 and 13 were isolated in excellent yields. Interestingly, arylation of methylene groups occurs with high diastereoselectivity favoring the anti diastereomers. Protected phenylalanine can be arylated by 4-iodoanisole to give 91% of the product 14 with crude diastereomer ratio 24:1. Similarly, arylation by 2-iodothiophene results in formation of a single diastereomer 15 in 95% yield. Protected lysine can be arylated by 4-iodoanisole and 2-iodothiophene in high yields and diastereoselectivities. Arylation of a leucine derivative affords products 18 and 19 in high yields. The reactions were typically run on a 0.5 mmol scale. A 5.55 mmol scale p-methoxyphenylation of the leucine derivative afforded 18 in 67% yield. Cleavage of directing group was investigated for 12 and 18. Methyl esters 20 and 21 were obtained in 80 and 58% yields, respectively. Compound 21 was produced in 86% ee that could be upgraded to 95% ee (85% recovery) by one recrystallization. Additionally, relative stereochemistry of 21, which is a derivative of highly constrained β-isopropyltyrosine,[13] was verified by X-ray crystallography. Scheme 3 Aminoquinoline Auxiliary. Preliminary results in alkylation and acetoxylation of amino acid C-H bonds are reported in Scheme 4. Thus, alanine derivative 11 was alkylated by 1-iodooctane affording 22 in 42% yield. Compound 22 is a derivative of a lipidic amino acid which has shown tumor cell growth inhibitor activity.[14] Acetoxylation of 23 gave 24 in 53% yield.[15–16] Scheme 4 Alkylation and Acetoxylation. The arylation diastereoselectivity is set either at the C-H activation or, less likely, at reductive elimination step.[17] The H/D exchange in 23 was examined by heating the substrate with catalytic Pd(OAc)2 in CD3CO2D-toluene-d8 mixture. (Scheme 5). After 5 hours at 100 °C, 64% of deuterium incorporation was observed at 3S position with minimal (<10%) incorporation at 3R position. A generalized reaction mechanism can be proposed. Formation of a palladium amide 23a is followed by the C-H activation that affords 23b. The complex 23b then can be protonated or deuterated leading to 25. Since protonation likely occurs with retention of configuration,[18] it can be assumed that 23b has a trans arrangement of phthaloyl and phenyl groups and that the diastereoselectivity of the arylation is set at the stage of palladation. Oxidative addition to give a high-valent[19] Pd intermediate 26 is followed by reductive elimination that proceeds with retention of configuration. Oxidative addition of aryl iodides to palladium(II) may be facilitated by the silver salts since they are known to complex aryl iodides.[20] Ligand exchange affords 27 and regenerates 23a. Scheme 5 Mechanistic Considerations. In conclusion, we have shown that synthesis of a number of substituted phenylalanine derivatives is possible by using C-H bond functionalization methodology. The syntheses are highly convergent and employ N-phthaloylalanine possessing a 2-thiomethylaniline directing group. The use of 8-aminoquinoline directing group allows for the diarylation of methyl and diastereoselective monoarylation of amino acid methylene groups. Acetoxylation and alkylation of amino acid derivative C-H bonds is also possible.

309 citations

Journal ArticleDOI
TL;DR: The reactivity and packing density of the MUA-NHSS esters are investigated in detail by reacting these intermediates with ammonia (NH3), and nearly all of theMUA molecules (∼80%) are converted to amides.
Abstract: A monolayer of poly(l-lysine) (PL) is attached covalently via amide bonds to an alkanethiol self-assembled monolayer (SAM) on a gold surface. The amide bond is formed in two steps: the terminal carboxylic acid groups of an 11-mercaptoundecanoic acid (MUA) SAM are first activated to the N-hydroxysulfosuccinimide (NHSS) ester, followed by reaction of this MUA-NHSS ester monolayer with the amino groups of PL to create multiple amide bond linkages to the surface. The reactivity and packing density of the MUA-NHSS esters are investigated in detail by reacting these intermediates with ammonia (NH3). In the NH3 experiments, approximately 50% of the carboxylic acids in the MUA monolayer are converted to amides during the first cycle of this two-step surface reaction. This reaction yield of 50% is limited by the steric packing of the NHSS ester intermediate. However, after three cycles of MUA activation to the NHSS ester and reaction with NH3, nearly all of the MUA molecules (∼80%) are converted to amides. Polari...

308 citations

Journal ArticleDOI
TL;DR: In this paper, two coordination polymers constructed from magnesium and the tetratopic organic linker 2,5-dihydroxyterephthalic acid are reported, denominated CPO-26-Mg and CPO27-mg.
Abstract: Two coordination polymers constructed from magnesium and the tetratopic organic linker 2,5-dihydroxyterephthalic acid are reported, denominated CPO-26-Mg and CPO-27-Mg. The organic component carries two different types of protic functional groups. The degree of deprotonation of the organic component can be regulated by the amount of sodium hydroxide employed in the synthesis, thus determining which of the compounds forms. In CPO-26-Mg, only the carboxylic acid groups of the linker are deprotonated and take part in the construction of the three-dimensional framework. The structure is non-porous, and its topology is based on the PtS net. In CPO-27-Mg, both the carboxylic acid and the hydroxy groups are deprotonated and involved in the construction of a microporous three-dimensional framework which is based on a honeycomb motif containing large solvent-filled channels. The metal atoms are arranged in chiral chains along the intersection of the honeycomb and contain one water molecule in their coordination sphere, which allows for the creation of coordinatively unsaturated metal sites upon dehydration. CPO-27-Mg is a potentially useful lightweight adsorbent with a pore volume of 60 % of the total volume of the structure and an apparent Langmuir surface area of up to 1030 m2 g–1. Its thermal stability was investigated by thermogravimetry and variable-temperature powder X-ray diffraction, which shows framework degradation to commence at 160 °C in air, at 235 °C under nitrogen, and at 430 °C in a dynamic vacuum. Thermogravimetric dehydration and re-hydration experiments at miscellaneous temperatures indicate that it is possible to obtain open metal sites in CPO-27-Mg, but the water is more tightly bound in this material than in the previously reported isostructural nickel compound.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

304 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023198
2022457
2021459
2020738
2019842
2018813