- Catalytic enantioselective synthesis of chiral phthalides by Sml 2-mediated reductive cyclization of 2-acylarylcarboxylates
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A significant new and efficient catalytic asymmetric approach for the highly enantioselective synthesis of chiral phthalides by SmI2-induced reductive cyclization of 2-acylarylcarbonylates was developed. The combination of (4S,5R)-4,5-diphenyloxazolidin-2-one and 2,2,6,6-tetramethylpiperidine was found to be a very effective catalyst system in the reaction. This method provides a ready access to a broad range of enantiomerically enriched phthalides (up to 99% ee). Copyright
- Huang, Ling-Lin,Xu, Ming-Hua,Lin, Guo-Qiang
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- An efficient direct asymmetric synthesis of 3-substituted phthalides
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A facile, two-step, asymmetric synthesis of 3-substituted phthalides has been developed. The enantiopure amide, obtained through coupling of 2-iodobenzoic acid with (S)-1-(pyrrolidin-2-ylmethyl)-1H-imidazole, was magnesiated using isopropylmagnesium chloride. Corresponding reactions with a range of aldehydes were carried out in situ by either direct addition or transmetallation using zinc(II) chloride. Intramolecular esterification of the adduct allowed the versatile asymmetric synthesis of phthalides in up to 88% enantiomeric excess. Georg Thieme Verlag Stuttgart.
- Zhang, Zhan-Bin,Lu, Yong-Qin,Duan, Xin-Fang
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- Efficient general asymmetric syntheses of 3-substituted 1(3H)-isobenzofuranones in very high enantiomeric excess
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The intermolecular asymmetric reduction of methyl o-(1-oxoalkyl)benzoates with B-chlorodiisopinocampheylborane provides, after workup, 3-alkylphthalides in ≥ 97% ee. Unfortunately, this procedure is not as efficient for the preparation of 3-arylphthalides. However, an intramolecular reduction of B-(o-benzoylbenzoyloxy)diisopinocampheylborane, readily prepared by the treatment of o-benzoyl benzoic acid with diisopinocampheylborane, provides 3-phenylphthalide in ≥ 96% ee.
- Ramachandran, P. Veeraraghavan,Chen, Guang-Ming,Brown, Herbert C.
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- Redox Enzyme Models. Catalysis of the Cathodic Cleavage of Benzyl Esters via Complexation with a Substituted β-Cyclodextrin
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β-Cyclodextrin substituted at the 6-position with an electrophore (o-benzoylbenzoate) complexes with benzyl esters and promotes their cleavage at the relatively modest reduction potential of the electrophore.
- Smith, Carmen Z.,Utley, James H. P.
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- Stereoselective synthesis of 3-substituted phtalides via asymmetric transfer hydrogenation using well-defined ruthenium catalysts under neutral conditions
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The asymmetric transfer hydrogenation of methyl 2-acylbenzoates and 2-propyl 3-acetylpyridine-2-carboxylate in 2-propanol, in the absence of base, with presynthesized Ru-{β-amino alcohol} or Ru-{TsDPEN} true catalysts provides 3-alkylphtalides in high yields and 92-97% ee. The procedure is, however, not as efficient for the preparation of optically active 3-phenylphtalide.
- Everaere, Kathelyne,Scheffler, Jean-Luc,Mortreux, André,Carpentier, Jean-Fran?ois
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- Laser flash photolysis study of the photochemistry of ortho- benzoylbenzaldehyde
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Ketene-enols 4 and 5 have been generated by laser flash photolysis of ortho-benzoylbenzaldehyde (3) and kinetically and spectroscopically characterized. In benzene or acetonitrile, the E ketene-enol, 4, shows absorption at 340 and 400 nm and a lifetime in excess of 1 ms, whereas the Z ketene-enol, 5, shows maxima at 360 and 430 nm and a lifetime of only 1.5 μs. At shorter time scales we observed a weak absorption λmax = 580 nm) tentatively assigned to biradical 6 with a lifetime of 140 ns. The E ketene-enol is readily quenched by oxygen, dienophiles, methanol, and water, with quenching rate constants ranging from 3.6 × 103 M -1 s-1 (for methanol as a quencher) to 2.2 × 10 8 MT-1 s-1 (for diethyl ketomalonate). At high water concentrations (typically > 10 M) a new species, 7, was detected showing maximum absorption at 5 10 nm and a growth lifetime of 7 μs. In deuterated water and using the same concentration as before we observed a formation lifetime for 7 of 10 μs, which results in an isotope effect of ~ 1.5. It is proposed that 5 is the main precursor for 7. Steady-state irradiation of 3 in deaerated methanol leads to the formation of dihydroanthraquinone (9), a strongly colored and fluorescent (λmax = 475 nm, τfl = 29 ns) species, whereas 3-phenylphthalide (2, R = Ph) is the main product when the irradiation is performed in benzene. Steady-state quenching of product formation by diethyl ketomalonate gives a Stern-Volmer constant of 380 MT-1 from which we conclude that 5 is the ketene-enol responsible for product formation, in agreement with the laser flash photolysis results.
- Netto-Ferreira,Scaiano
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- Mechanistic insight into the synergistic Cu/Pd-catalyzed carbonylation of aryl iodides using alcohols and dioxygen as the carbonyl source
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Pd-catalyzed carbonylation, as an efficient synthetic approach to the installation of carbonyl groups in organic compounds, has been one of the most important research fields in the past decade. Although elegant reactions that allow highly selective carbonylations have been developed, straightforward routes with improved reaction activity and broader substrate scope remain long-term challenges for new practical applications. Here, we show a new type of synergistic Cu/Pd-catalyzed carbonylation reaction using alcohols and dioxgen as the carbonyl sources. A broad range of aryl iodides and alcohols are compatible with this protocol. The reaction is concise and practical due to the ready availability of the starting materials and the scalability of the reaction. In addition, the reaction affords lactones and lactams in an intermolecular fashion. Moreover, DFT calculations have been performed to study the detailed mechanisms. [Figure not available: see fulltext.]
- Li, Junxuan,Zhou, Jinlei,Wang, Yumei,Yu, Yue,Liu, Qiang,Yang, Tilong,Chen, Huoji,Cao, Hua
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- Access to Diarylmethanols by Wittig Rearrangement of ortho-, meta-, and para-Benzyloxy- N-Butylbenzamides
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The N-butyl amide group, CONHBu, has been found to be an effective promoter of the [1,2]-Wittig rearrangement of aryl benzyl ethers and thus allow the two-step synthesis of isomerically pure substituted diarylmethanols starting from simple hydroxybenzoic acid derivatives. The method is compatible with a wide range of functional groups including methyl, methoxy, and fluoro, although not with nitro and, unexpectedly, is applicable to meta as well as ortho and para isomeric series.
- Aitken, R. Alan,Harper, Andrew D.,Inwood, Ryan A.,Slawin, Alexandra M. Z.
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supporting information
p. 4692 - 4701
(2022/04/07)
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- Enantioselective synthesis of 3-aryl-phthalides through a nickel-catalyzed stereoconvergent cross-coupling reaction
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A nickel-catalyzed asymmetric Suzuki-Miyaura cross-coupling of racemic 3-bromo-phthalides and arylboronic acids was realized for the synthesis of diverse chiral 3-aryl-phthalides in moderate to excellent reaction yields. The reaction proceeded in a stereoconvergent manner and high enantioselectivities were observed for most examined examples. A number of functional groups like aldehyde, ester and bromide were well tolerated. Heteroaromatic boronic acids were also competent coupling partners in this reaction.
- Feng, Chen-Guo,Xu, Si-Yu,Zhang, Rui,Zhang, Shu-Sheng
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p. 4492 - 4496
(2021/05/31)
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- Binaphthyl-prolinol chiral ligands: Design and their application in enantioselective arylation of aromatic aldehydes
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Binaphthyl-prolinol ligands were designed and applied in enantioselective arylation of aromatic aldehydes and sequential arylation-lactonization of methyl 2-formylbenzoate. Under optimized conditions, the reactions provided the desired diarylmethanols and 3-aryl phthalides in up to 96% yields with up to 99% ee and up to 89% yields with up to 99% ee, respectively. In particular, essentially optically pure 3-aryl phthalides (over 99% ee) were obtained in large quantities through recrystallization. This journal is
- Yao, Chao,Chen, Yaoqi,Sun, Ruize,Wang, Chao,Huang, Yue,Li, Lin,Li, Yue-Ming
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supporting information
p. 3644 - 3655
(2021/05/04)
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- Metal-Free Cascade Formation of Intermolecular C-N Bonds Accessing Substituted Isoindolinones under Cathodic Reduction
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An electrochemical protocol for the construction of substituted isoindolinones via reduction/amidation of 2-carboxybenzaldehydes and amines has been realized. Under metal-free and external-reductant-free electrolytic conditions, the reaction achieves the cascade formation of intermolecular C-N bonds and provides a series of isoindolinones in moderate to good yields. The deuterium-labeling experiment proves that the hydrogen in the methylene of the product is mainly provided by H2O in the system.
- Zou, Zirong,Cai, Genuo,Chen, Weihao,Zou, Canlin,Li, Yamei,Wu, Hongting,Chen, Lu,Hu, Jinhui,Li, Yibiao,Huang, Yubing
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supporting information
p. 15777 - 15784
(2021/11/17)
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- Visible Light-Promoted Magnesium, Iron, and Nickel Catalysis Enabling C(sp3)-H Lactonization of 2-Alkylbenzoic Acids
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A mild and practical C(sp3)-H lactonization protocol has been achieved by merging photocatalysis and magnesium (iron, nickel) catalysis. A diverse range of 2-alkylbenzoic acids with a variety of substitution patterns could be transformed into the corresponding phthalide products. Based on the mechanistic experimentation and reported prior studies, a possible mechanism for the benzylic oxidative lactonization reaction was proposed with the hypothetic photoactive ternary complex formed between the 2-alkylbenzoic acid substrate, magnesium ion, and bromate anion.
- Li, Sasa,Su, Mincong,Sun, Jie,Hu, Kunjun,Jin, Jian
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supporting information
p. 5842 - 5847
(2021/07/31)
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- Efficient One-Pot Synthesis of 3-Substituted Phthalides via Additive Arylation of Organozinc Intermediate
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In recent years, substitution at the third position on phthalides has been proven a valua-ble synthetic intermediate for developing active molecules. We reported a direct and efficient one-pot method for the synthesis of 3-aryl Phthalides performed by adding organo-zinc reagent on methyl-2-formylbenzoate; reagent formed in-situ by the reaction between diethylzinc and different aryl boronic acid derivatives without using any ligand. The possible mechanism involved a coordi-nated zinc carbonyl transition state, arylation, and followed by the intramolecular cyclization. The substituents groups in boronic having different electronic and steric properties played an important role in the reaction completion time and yield. The structure elucidation and confirmation of the synthesized compounds were done by using H-NMR analytical data. The method can be useful for synthesizing various scaffolds and intermediates in search of potentially active compounds.
- Hasan, Mohsin,Tonk, Rajiv Kumar,Yadav, Vivek
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p. 783 - 789
(2022/02/17)
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- Direct and selective synthesis of 3-arylphthalides via nickel-catalyzed aryl addition/intramolecular esterification
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Herein we report a nickel-catalyzed aryl addition/intramolecular esterification in a cascade fashion. Under the combination of commercially available nickel precursor and tridentate ligand, the one pot protocol offers a direct, simple and regioselective approach to access 3-aryl phthalide derivatives from two readily available substrates with good efficiency, broad scope as well as satisfactory functional group compatibility.
- Qiang, Qing,Liu, Feipeng,Rong, Zi-Qiang
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supporting information
(2021/05/10)
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- Cationic Iridium/Chiral Bisphosphine-Catalyzed Enantioselective Hydroacylation of Ketones
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A facile and convenient synthesis of the chiral phthalide framework catalyzed by cationic iridium was developed. The method utilized cationic iridium/bisphosphine-catalyzed asymmetric intramolecular carbonyl hydroacylation of 2-keto benzaldehydes to furnish the corresponding optically active phthalide products in good to excellent enantioselectivities (up to 98% ee). The mechanistic studies using a deuterium-labelled substrate suggested that the reaction involved an intramolecular carbonyl insertion mechanism to iridium hydride intermediate. In addition, we investigated the kinetic isotope effect (KIE) of intramolecular hydroacylation with deuterated substrate and determined that the C?H activation step is not included in the turnover-limiting step.
- Shirai, Tomohiko,Iwasaki, Tomoya,Kanemoto, Kazuya,Yamamoto, Yasunori
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supporting information
p. 1858 - 1862
(2020/06/02)
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- Rhodium(III)-Catalyzed Asymmetric Addition of Inert Arene C-H Bond to Aldehydes to Afford Enantioenriched Phthalides
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An asymmetric rhodium(III)-catalyzed Grignard-type addition of inert arene C-H bond to aldehydes is reported. It provides a new strategy for the synthesis of chiral 3-substituted phthalides in good yields (up to 87%) with high enantiomeric purity (up to 99% ee). Interestingly, a chiral-matching effect between substrate and catalyst was observed, which is crucial to accomplish satisfied reaction outcomes. Mechanistically, the reaction is assumed to proceed via consecutive C(sp2)-H activation of benzamide, addition to aldehyde, and lactonization.
- Chen, Wenkun,Li, Jie,Xie, Hui,Wang, Jun
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supporting information
p. 3586 - 3590
(2020/04/20)
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- Highly Enantioselective Cobalt-Catalyzed Hydroboration of Diaryl Ketones
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A highly enantioselective cobalt-catalyzed hydroboration of diaryl ketones with pinacolborane was developed using chiral imidazole iminopyridine as a ligand to access chiral benzhydrols in good to excellent yields and ee. This protocol could be carried out in a gram scale under mild reaction conditions with good functional group tolerance. Chiral biologically active 3-substituted phthalide and (S)-neobenodine could be easily constructed through asymmetric hydroboration as a key step.
- Liu, Wenbo,Guo, Jun,Xing, Shipei,Lu, Zhan
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supporting information
p. 2532 - 2536
(2020/04/02)
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- Palladium-Catalyzed Decarboxylative ortho-C(sp2)?H Aroylation of N-Sulfoximine Benzamides at Room Temperature
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A palladium-catalyzed method for the decarboxylative ortho C?H acylation of N-sulfoximine benzamides is developed at room temperature. The catalytic method enables easy access to various functionalized 2-aroylaromatic carboxylic acid derivatives in good isolated yields. Based on our mechanistic studies, a Pd(II)/Pd(IV) catalytic cycle that involves aroyl radical intermediate is proposed for the reaction.
- Das, Prasenjit,Biswas, Promita,Guin, Joyram
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p. 920 - 925
(2020/03/04)
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- (Cyclopentadienone)iron-Catalyzed Transfer Dehydrogenation of Symmetrical and Unsymmetrical Diols to Lactones
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Air-stable iron carbonyl compounds bearing cyclopentadienone ligands with varying substitution were explored as catalysts in dehydrogenative diol lactonization reactions using acetone as both the solvent and hydrogen acceptor. Two catalysts with trimethylsilyl groups in the 2- A nd 5-positions, [2,5-(SiMe3)2-3,4-(CH2)4(δ4-C4C= O)]Fe(CO)3 (1) and [2,5-(SiMe3)2-3,4-(CH2)3(δ4-C4C= O)]Fe(CO)3 (2), were found to be the most active, with 2 being the most selective in the lactonization of diols containing both primary and secondary alcohols. Lactones containing five-, six-, and seven-membered rings were successfully synthesized, and no over-oxidations to carboxylic acids were detected. The lactonization of unsymmetrical diols containing two primary alcohols occurred with catalyst 1, but selectivity was low based on alcohol electronics and modest based on alcohol sterics. Evidence for a transfer dehydrogenation mechanism was found, and insight into the origin of selectivity in the lactonization of 1°/2° diols was obtained. Additionally, spectroscopic evidence for a trimethylamine-ligated iron species formed in solution during the reaction was discovered.
- Tang, Yidan,Meador, Rowan I. L.,Malinchak, Casina T.,Harrison, Emily E.,McCaskey, Kimberly A.,Hempel, Melanie C.,Funk, Timothy W.
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p. 1823 - 1834
(2020/02/04)
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- Base-Directed Photoredox Activation of C-H Bonds by PCET
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Photoredox catalysis using proton-coupled electron transfer (PCET) has emerged as a powerful method for bond transformations. We previously employed traditional chemical oxidants to achieve multiple-site concerted proton-electron transfer (MS-CPET) activation of a C-H bond in a proof-of-concept fluorenyl-benzoate substrate. As described here, photoredox oxidation of the fluorenyl-benzoate follows the same rate constant vs driving force trend determined for thermal MS-CPET. Analogous photoredox catalysis enables C-H activation and H/D exchange in a number of additional substrates with favorably positioned bases. Mechanistic studies support our hypothesis that MS-CPET is a viable pathway for bond activation for substrates in which the C-H bond is weak, while stepwise carboxylate oxidation and hydrogen atom transfer likely predominate for stronger C-H bonds.
- Ener, Maraia E.,Darcy, Julia W.,Menges, Fabian S.,Mayer, James M.
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supporting information
p. 7175 - 7180
(2020/07/14)
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- The detection of the precursors of the photorearranged products of 3-hydroxyflavones in selected solvents from UV-visible spectra: In situ
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Mechanistic studies relating to the photochemistry of 3-hydroxy-2-phenyl-4H-chromen-4-one (3HF) and 6-chloro-3-hydroxy-2-phenyl-4H-chromen-4-one (Cl-3HF) have been reinvestigated in selected solvents. The UV-visible spectra of the photoproduct(s) of 3HF and Cl-3HF have been computed in situ via subtracting the spectra of unreacted substrates, with acetonitrile (ACN) and methanol (MeOH) as solvents. These spectra turn out to be different from the spectra of the corresponding isolated photoproducts: 3-hydroxy-3-phenyl-indan-1,2-dione and 6-chloro-3-hydroxy-3-phenyl-indan-1,2-dione (referred to as dione). Analyses of the photoproduct(s) via GC-MS show the formation of a single detectable product, i.e., the corresponding dione. On the basis of some experimental observations, it is proposed that the primary photoproduct in situ is 2,3-epoxy-2-hydroxy-1-indanone (referred to as epoxide) instead of dione as reported in previous years. Earlier, epoxide has been proposed to be the intermediate in the mechanism for the formation of dione. This is the first report where the formation of epoxide has been directly detected in the selected solvents. On the other hand, both dione and epoxide (2?:?1) are shown to be formed with MeOH as solvent. The second important finding is that epoxide and dione interconvert in the dark, depending upon the environment. With ACN as solvent, pure dione in the dark is kinetically and partially converted to epoxide. With MeOH as solvent, epoxide is instantly and partially converted to dione until both are in equilibrium. However, a solution of dione in MeOH remains stable in the dark. The photoformation of epoxide is quantitative with ACN as solvent and it is sufficiently stable. It has been further observed that epoxide solutions of 3HF and Cl-3HF in ACN are quantitatively converted into 3-phenylisobenzofuran-1(3H)-one and 6-chloro-3-phenylisobenzofuran-1(3H)-one, i.e., the corresponding phthalides, through the loss of CO when kept in the dark for some days. A mechanism has been proposed where epoxide has been shown to give dione and/or phthalide via selective C-O or C-C bond cleavage in the oxiranyl ring, respectively. The selection of this cleavage depends mainly on the solvent system and the substituents in the parent flavones.
- Tomar, Jyoti,Kaur, Kulvir,Bansal, Manisha
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p. 2912 - 2920
(2019/12/24)
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- Catalytic asymmetric synthesis of 3-aryl phthalides enabled by arylation-lactonization of 2-formylbenzoates
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The catalytic asymmetric synthesis of 3-aryl phthalides is reported through a sequential asymmetric arylation-lactonization reaction. The reaction is enabled by a boron-zinc exchange to generate reactive arylating agents, which react with 2-formylbenzoates in the presence of a chiral amino naphthol ligand. The enantiodetermining step is the arylation of the aldehyde, which then undergoes a lactonization event to yield the corresponding phthalides in good yields and enantioselectivities.
- Carlos, Andressa M. M.,Stieler, Rafael,Lüdtke, Diogo S.
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supporting information
p. 283 - 289
(2019/01/10)
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- Catalytic asymmetric 1,2-Addition/Lactonization tandem reactions for the syntheses of chiral 3-Substituted phthalides using organozinc reagents
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Using chiral phosphoramide ligand 2d-Zn (II) complex derived from (1R,2R)-1,2-diphenylethylenediamine as the catalyst, we have developed efficient catalytic asymmetric 1,2-addition/lactonization tandem reactions of diverse organozinc reagents with varied methyl 2-formylbenzoates for the construction of optically enriched 3-aryl or alkyl substituted phthalides, which are significant building blocks of many important chiral pharmaceuticals and natural products. The corresponding products could be afforded with good to excellent yields (up to 95%) and moderate to good enantioselectivities (up to 89%).
- Huang, Huayin,Wang, Yabai,Zong, Hua,Song, Ling
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- Rhenium-Catalyzed Phthalide Synthesis from Benzamides and Aldehydes via C-H Bond Activation
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The [4 + 1] annulation of benzamides and aldehydes for phthalide synthesis was achieved via rhenium-catalyzed C-H activation, which demonstrates an unprecedented reaction pattern distinct from those of other transition-metal catalyses. The reaction also features readily available starting materials, a wide scope for both electro-rich and electro-deficient substrates, and the elimination of homoannulation byproducts.
- Jia, Bing,Yang, Yunhui,Jin, Xiqing,Mao, Guoliang,Wang, Congyang
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p. 6259 - 6263
(2019/09/06)
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- Palladium-Catalyzed Direct Oxidative Coupling of Iodoarenes with Primary Alcohols Leading to Ketones: Application to the Synthesis of Benzofuranones and Indenones
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In the present study, a palladium-catalyzed direct oxidative acylation through cross-dehydrogenative coupling has been investigated, utilizing readily available primary alcohols as acylating sources. Overall, this oxidative coupling proceeds via three distinct transformations such as oxidation, radical formation, and cross-coupling in one catalytic process. This protocol does not involve the assistance of a directing group or activation of the carbonyl group by any other means. Furthermore, this reaction made use of no toxic CO gas as carbonylating agent; instead, feedstock primary alcohols have been utilized as acylation source. Notably, the synthesis of benzofuranones and indenones is enabled. This strategy was also applied to the synthesis of n-butylphthalide, fenofibrate, pitofenone, and neo-lignan.
- Suchand, Basuli,Sreenivasulu, Chinnabattigalla,Satyanarayana, Gedu
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p. 4832 - 4843
(2019/07/31)
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- Introducing the Chiral Transient Directing Group Strategy to Rhodium(III)-Catalyzed Asymmetric C?H Activation
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The chiral transient directing group (TDG) strategy has been successfully introduced to the rhodium(III)-catalyzed asymmetric C?H activation. In the presence of a catalytic amount of a chiral amine and an achiral rhodium catalyst, various chiral phthalides were synthesized from simple aldehydes with high chemoselectivity, regioselectivity, and enantioselectivity (53 examples, up to 73 % yield and >99 % ee). It is noteworthy that the chiral induction model is different from the previously reported chiral TDG system using amino acid derivatives and palladium salts. The imino group generated in situ from chiral amine and aldehyde acts as the monodentate TDG to promote the C?H activation, stereoselectively generating the chiral rhodacycle bearing a chiral metal center. Moreover, the stereogenic center of the product is created and stereocontrolled during the Grignard-type addition of the C?Rh bond to aldehyde, rather than during the C?H activation step.
- Li, Guozhu,Jiang, Jijun,Xie, Hui,Wang, Jun
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supporting information
p. 4688 - 4694
(2019/03/17)
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- Cooperative iodine and photoredox catalysis for direct oxidative lactonization of carboxylic acids
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A new method for the formation of γ- and δ-lactones from carboxylic acids through direct conversion of benzylic C-H to C-O bonds is described. The reaction is conveniently induced by visible light and relies on a mild cooperative catalysis by the combination of molecular iodine and an organic dye.
- Duhamel, Thomas,Mu?iz, Kilian
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supporting information
p. 933 - 936
(2019/01/23)
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- Metal-Free Aerobic Oxidative C–O Coupling of C(sp3)–H with Carboxylic Acids Catalyzed by DDQ and tert-Butyl Nitrite
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The formation of the C–O bond is one of the hot topics in the area of C(sp3)–H bond functionalization. A metal-free oxidative cross-coupling between benzylic C(sp3)–H bond and carboxylic acids has been developed. The reactions were performed with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as the catalyst, tert-butyl nitrite (TBN) as the co-catalyst, and molecular oxygen as the terminal oxidant. A variety of diarylmethanes could be successfully coupled with various carboxylic acids to obtain diarylmethanol esters in good to excellent yields. In addition, 2-benzylbenzoic acids could be converted into phthalides in moderate yields through an intramolecular oxidative cyclization.
- Pan, Decheng,Pan, Zilong,Hu, Zhiming,Li, Meichao,Hu, Xinquan,Jin, Liqun,Sun, Nan,Hu, Baoxiang,Shen, Zhenlu
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p. 5650 - 5655
(2019/08/20)
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- Pd-Catalyzed debenzylation and deallylation of ethers and esters with sodium hydride
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Herein we demonstrate simply that the addition of Pd(OAc)2 as a promotor switches the reactivity of a commonly used base NaH to a nucleophilic reductant. The reactivity is engineered into a palladium-catalyzed reductive debenzylation and deallylation of aryl ethers and esters. This operationally simple, mild protocol displays a broad substrate scope and a broad spectrum of functional group tolerance (>50 examples) and high chemoselectivity toward aryl ethers over aliphatic structures. Moreover, the dual reactivity of NaH as a base and a reductant is demonstrated in efficient synthetic elaboration.
- Mao, Yujian,Liu, Ye,Hu, Yanwei,Wang, Liang,Zhang, Shilei,Wang, Wei
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p. 3016 - 3020
(2018/04/14)
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- Diversity-Oriented Synthesis of Heterocycles: Al(OTf)3-Promoted Cascade Cyclization and Ionic Hydrogenation
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An efficient and facile method has been developed for the diversity-oriented synthesis of heterocycles. Hexahydrophenoxazines, tetrahydroquinolines, indolines, hexahydrocarbazoles, and lactones were conducted via Al(OTf)3-promoted cascade cyclization and ionic hydrogenation. Furthermore, this protocol was utilized to smoothly prepare piracetam and its key intermediate as well.
- Liu, Tianqi,Jia, Wenqiang,Xi, Qiumu,Chen, Yonghui,Wang, Xiaojian,Yin, Dali
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p. 1387 - 1393
(2018/02/10)
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- Indium-Catalyzed Direct Conversion of Lactones into Thiolactones and Selenolactones in the Presence of Elemental Sulfur and Selenium
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The direct conversion of lactones into thiolactones with elemental sulfur (S 8) catalyzed by InCl 3 /PhSiH 3 in a one-pot reaction is described. This catalytic system was successfully applied to the novel preparation of selenolactones from lactones and selenium.
- Sakai, Norio,Horikawa, Shuhei,Ogiwara, Yohei
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p. 565 - 574
(2017/12/26)
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- Controlled photo-flow oxidative reaction (UV-FOR) platform for ultra-fast phthalide and API synthesis
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An integrated photo-flow oxidative reaction (UV-FOR) platform approach is presented for the synthesis of phthalides. The current protocol is catalyst-free, and uses economical and abundant hydro-carbons and hydrocarbon derivatives such as benzoic acid, benzene, and xylene, as starting materials. The reaction is performed using oxygen as a green oxidant in a time- and labour-efficient manner. This integrated approach has been shown to be successful in making a UV-FOR platform suitable for the on-demand synthesis of phthalides and their further syntheses to 2-arylmethylbenzoic acids and arylogous Michael addition products under relatively mild conditions. The current protocol was further extended to the gram scale synthesis of an ischemic stroke-relevant active pharmaceutical ingredient (API), 3-N-butylphthalide (NBP), in a continuous flow process.
- Aand, Dnyaneshwar,Karekar, Sanjeev,Mahajan, Bhushan,Pawar, Amit B.,Singh, Ajay K.
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supporting information
p. 4584 - 4590
(2018/10/23)
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- Carboxylate-Directed Addition of Aromatic C-H Bond to Aromatic Aldehydes under Ruthenium Catalysis
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We report that ruthenium complexes effectively catalyzed the carboxylate-directed addition of aromatic C-H bonds to aldehydes. The reactions of aromatic acids with a variety of aromatic aldehydes including unactivated ones proceeded efficiently to give the corresponding isobenzofuranone derivatives in high yields. The combination of ruthenium(II) complexes with tricyclohexylphosphine led to highly nucleophilic aryl-metal species, which enabled versatile [3 + 2] cycloaddition in the absence of a Lewis acid. This paper also demonstrates the application of supported ruthenium catalysts to the title reaction.
- Miura, Hiroki,Terajima, Sachie,Shishido, Tetsuya
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p. 6246 - 6254
(2018/06/11)
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- Reductive Heterocyclization of 2-Cyanobenzophenones by the Action of NaBH4. New Efficient Synthesis of 3-Arylphthalides
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The reduction of 2-cyclopropylcarbonyl-, 2-(thiophen-2-yl)carbonyl-, and 2-arylcarbonylbenzonitriles with sodium tetrahydridoborate afforded 3-cyclopropyl-, 3-(2-thiophen-2-yl)-, and 3-arylphthalides, respectively, in high yields. Under analogous conditions, 3-cyanobenzophenones were converted to the corresponding 3-cyanobenzhydrols.
- Mochalov,Fedotov,Trofimova,Zefirov
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p. 568 - 572
(2018/06/11)
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- Visible-Light-Induced C-O Bond Formation for the Construction of Five- and Six-Membered Cyclic Ethers and Lactones
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Visible-light-induced intramolecular C-O bond formation was developed using 2,4,6-triphenylpyrylium tetrafluoroborate (TPT), which allows the regiocontrolled construction of cyclic ethers and lactones. The reaction is likely to proceed through the single-electron oxidation of the phenyl group, followed by the formation of a benzylic radical, thus preventing a competing 1,5-hydrogen abstraction pathway. Detailed mechanistic studies suggest that molecular oxygen is used to trap the radical intermediate to form benzyl alcohol, which undergoes cyclization. This new approach serves as a powerful platform by providing efficient access to valuable five- and six-membered cyclic ethers and lactones with a unified protocol.
- Im, Honggu,Kang, Dahye,Choi, Soyeon,Shin, Sanghoon,Hong, Sungwoo
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supporting information
p. 7437 - 7441
(2018/11/27)
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- Scalable Electrochemical Dehydrogenative Lactonization of C(sp2/sp3)-H Bonds
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A practical, electrochemical method is developed for the direct dehydrogenative lactonization of C(sp2/sp3)-H bonds under external oxidant- and metal-free conditions, delivering diverse lactones, including coumarin derivatives with excellent regioselectivity. The scalable nature of this newly developed electrochemical process was demonstrated on a 40 g scale following an operationally simple protocol. The remote lactonization of C(sp3)-H bonds would constitute an important synthetic advance toward electrochemical C-O bond formation.
- Zhang, Sheng,Li, Lijun,Wang, Huiqiao,Li, Qian,Liu, Wenmin,Xu, Kun,Zeng, Chengchu
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supporting information
p. 252 - 255
(2018/01/17)
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- Incorporation of carbon dioxide into phthalides: Via ligand-free copper-catalyzed direct carboxylation of benzoxasiloles
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The direct carboxylation of benzoxasiloles with carbon dioxide proceeded smoothly under mild conditions using copper iodide as a catalyst to afford phthalides after an acid work-up. Broad substrate scope and application of this methodology for the synthesis of natural products highlight the synthetic utility of this protocol.
- Nguyen, Thanh V. Q.,Rodríguez-Santamaría, José A.,Yoo, Woo-Jin,Kobayashi, Shu
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p. 2501 - 2505
(2017/07/17)
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- Ruthenium-Catalyzed Enantioselective Hydrogenation/Lactonization of 2-Acylarylcarboxylates: Direct Access to Chiral 3-Substituted Phthalides
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Highly enantioselective tandem hydrogenation/lactonization of various 2-acylarylcarboxylates including 2-aroylarylcarboxylates were realized by using [RuCl(benzene)(S)-SunPhos]Cl as the catalyst under mild reaction conditions. Excellent enantioselectivities (up to 99.6 % ee) and activities (S/C=1000) were obtained. This convenient and practical method enables a direct access to a series of highly optically pure 3-substituted phthalides that are very important molecules as valuable pharmacological compounds and diversified synthons for medicinal chemistry. Moreover, a gram-scale reaction was performed to further demonstrate the practicality of this approach.
- Lu, Bin,Zhao, Mengmeng,Ding, Guangni,Xie, Xiaomin,Jiang, Lili,Ratovelomanana-Vidal, Virginie,Zhang, Zhaoguo
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p. 3989 - 3996
(2017/09/13)
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- Lewis acid-assisted dirhodium(II)-catalyzed ketone hydroacylation
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The combination of a Rh(II) salt and a Lewisacid, Sc(OTf)3, as a highly active and robust cooperative catalyst system for ketone hydroacylation was developed. The catalyst system showed high turnover numbers (up to ca. 400) even under air, whereas the corresponding Rh(I)/Sc(OTf)3 system did not work well. The application of the Rh(II)/Sc system was also extended to hydroacylation of olefins and an enantioselective reaction.
- Yasukawa, Tomohiro,Kobayashi, Shu
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supporting information
p. 98 - 100
(2017/02/10)
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- Gallium-catalyzed reductive lactonization of γ-keto acids with a hydrosilane
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Described herein is the GaCl3-catalyzed lactonization of γ-keto carboxylic acids in the presence of PhSiH3 leading to the direct preparation of γ-lactone derivatives. This reducing system showed a relatively wide functional group tolerance.
- Sakai, Norio,Horikawa, Shuhei,Ogiwara, Yohei
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p. 81763 - 81766
(2016/09/09)
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- Palladium-Catalyzed Environmentally Benign Acylation
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Recent trends in research have gained an orientation toward developing efficient strategies using innocuous reagents. The earlier reported transition-metal-catalyzed carbonylations involved either toxic carbon monoxide (CO) gas as carbonylating agent or functional-group-assisted ortho sp2 C-H activation (i.e., ortho acylation) or carbonylation by activation of the carbonyl group (i.e., via the formation of enamines). Contradicting these methods, here we describe an environmentally benign process, [Pd]-catalyzed direct carbonylation starting from simple and commercially available iodo arenes and aldehydes, for the synthesis of a wide variety of ketones. Moreover, this method comprises direct coupling of iodoarenes with aldehydes without activation of the carbonyl and also without directing group assistance. Significantly, the strategy was successfully applied to the synthesis n-butylphthalide and pitofenone.
- Suchand, Basuli,Satyanarayana, Gedu
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p. 6409 - 6423
(2016/08/16)
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- Copper-Catalyzed Oxidative Cyclization of Carboxylic Acids
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A method for converting C-H to C-O bonds through oxidative cyclization of carboxylic acids to generate lactone products is described. The reaction employs catalytic amounts of Cu(OAc)2 and potassium persulfate as the terminal oxidant and is performed open to air in an aqueous acetic acid solvent system. Preliminary mechanistic studies suggest that substrate oxidation likely proceeds by sulfate radical anion and that the Cu catalyst has no influence on the product-determining step. These conclusions differ from related investigations that propose the intermediacy of a carboxylate radical.
- Sathyamoorthi, Shyam,Du Bois
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supporting information
p. 6308 - 6311
(2016/12/23)
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- Visible-Light Photocatalytic Aerobic Benzylic C(sp3)?H Oxygenations with the 3DDQ*/tert-Butyl Nitrite Co-catalytic System
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Photocatalytic aerobic benzylic C(sp3)?H oxygenations of aromatic hydrocarbons and C3-substituted indoles were studied by employing a co-catalytic system of 3DDQ* (DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone) and tert-butyl nitrite. The superior efficiency of these reaction conditions was demonstrated by comparison with the analogous thermal protocol, and a range of substrates could be oxidized catalytically and selectively in good yields.
- Rusch, Fabian,Schober, Jan-Christian,Brasholz, Malte
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p. 2881 - 2884
(2016/09/28)
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- Convenient in-flow preparation of Cr(II) chloride for Nozaki-Hiyama-Kishi reaction
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A flow preparation of chromous chloride has been introduced as a viable alternative to the batch protocol. Activity of the prepared reagent has been demonstrated in the traditional Nozaki-Hiyama-Kishi reaction.
- Voltrova, Svatava,Srogl, Jiri
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supporting information
p. 2473 - 2477
(2015/11/09)
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- Enantioselective addition of arylboronic acids to methyl 2-formylbenzoates by using a ruthenium/Me-BIPAM catalyst for synthesis of chiral 3-aryl-isobenzofuranones
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Ruthenium/Me-BIPAM-catalyzed asymmetric addition of arylboronic acids to methyl 2-formylbenzoates afforded chiral 3-aryl-isobenzofuranones. [RuCl2(p-cymene)]2/Me-BIPAM and RuCl2(PPh3)3/Me-BIPAM catalyst systems tolerate a variety of functional groups and give high yields with high enantioselectivities.
- Yohda, Masaaki,Yamamoto, Yasunori
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p. 10874 - 10880
(2015/11/17)
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- Nickel(0)-Catalyzed Enantio- and Diastereoselective Synthesis of Benzoxasiloles: Ligand-Controlled Switching from Inter- to Intramolecular Aryl-Transfer Process
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A highly enantioselective synthesis of 3-aryl-, vinyl-, and alkynyl-2,1-benzoxasiloles (up to 99.9% ee and 99% yield) was achieved via the sequential activation of an aldehyde and a silane by nickel(0). This strategy was applied to a simultaneous generation of carbon- and silicon-stereogenic centers with excellent selectivity (dr = 99:1) via diastereotopic aryl transfer. Initial mechanistic studies revealed the complete switching of an aryl-transfer process from an intermolecular (racemic synthesis in the presence of IPr) to an intramolecular (enantioselective synthesis using chiral NHC, L5) fashion. A plausible rationale for the switching of the aryl-transfer process is given by a preliminary DFT calculation, which suggests that the coordination of 1 to the nickel(0)/L5 fragment in an 2-arene:2-aldehyde fashion would be a key to the intramolecular process, while the formation of the corresponding intermediate is not possible in the presence of IPr. Owing to the chemically labile nature of its C-Si and O-Si bonds, enantioenriched benzoxasiloles are utilized for the synthesis of chiral building blocks and antihistaminic and anticholinergic drug molecules such as (R)-orphenadrine and (S)-neobenodine with no erosion of the enantiomeric excess.
- Kumar, Ravindra,Hoshimoto, Yoichi,Yabuki, Hayato,Ohashi, Masato,Ogoshi, Sensuke
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supporting information
p. 11838 - 11845
(2015/09/28)
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- Cu-MEDIATED ANNULATION FOR THE EFFECTIVE SYNTHESIS OF 3-SUBSTITUTED PHTHALIDES
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The present invention disclosed herein is a novel commercially feasible, one pot synthesis of library of 3-substituted phthalides of formula I via CuCN mediated oxidative cyclization in high yield. Formula I
- -
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Page/Page column 0072; 0112; 0113
(2015/02/25)
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- Solvent effects on the photophysics and photoreactivity of 3-hydroxyflavone: A combined spectroscopic and kinetic study
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The photophysical and photochemical properties of 3-hydroxyflavone (3HF) have been investigated in six solvents with different chemical and physical properties: methanol, 2,2,2-trifluoroethanol (TFE), tetrahydrofuran (THF), chloroform (CHCl3), acetonitrile (MeCN), and dimethylsulfoxide (DMSO). The polarity of the solvents and their ability to interact with 3HF by donating and accepting hydrogen bonds were found to strongly influence the UV-Vis absorption spectra and the emission spectra, as well as other photophysical parameters such as fluorescence quantum yield and fluorescence lifetime. In addition, the nature of the solvent was found to influence the kinetics of 3HF photorearrangement to 3-hydroxy-3-phenyl-1,2 indiandione, the reaction being the fastest in TFE, and the slowest in DMSO. The results were interpreted in terms of specific solute-solvent interactions.
- Protti, Stefano,Mezzetti, Alberto
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p. 110 - 114
(2015/05/05)
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- From in vitro to in cellulo: Structure-activity relationship of (2-nitrophenyl)methanol derivatives as inhibitors of PqsD in Pseudomonas aeruginosa
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Recent studies have shown that compounds based on a (2-nitrophenyl)methanol scaffold are promising inhibitors of PqsD, a key enzyme of signal molecule biosynthesis in the cell-to-cell communication of Pseudomonas aeruginosa. The most promising molecule displayed anti-biofilm activity and a tight-binding mode of action. Herein, we report on the convenient synthesis and biochemical evaluation of a comprehensive series of (2-nitrophenyl)methanol derivatives. The in vitro potency of these inhibitors against recombinant PqsD as well as the effect of selected compounds on the production of the signal molecules HHQ and PQS in P. aeruginosa were examined. The gathered data allowed the establishment of a structure-activity relationship, which was used to design fluorescent inhibitors, and finally, led to the discovery of (2-nitrophenyl)methanol derivatives with improved in cellulo efficacy providing new perspectives towards the application of PqsD inhibitors as anti-infectives. This journal is the Partner Organisations 2014.
- Storz, Michael P.,Allegretta, Giuseppe,Kirsch, Benjamin,Empting, Martin,Hartmann, Rolf W.
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supporting information
p. 6094 - 6104
(2014/08/05)
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- Cobalt-catalyzed enantioselective intramolecular hydroacylation of ketones and olefins
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Cobalt-chiral diphoshine catalytic systems promote intramolecular hydroacylation reactions of 2-acylbenzaldehydes and 2-alkenylbenzaldehydes to afford phthalide and indanone derivatives, respectively, in moderate to good yields with high enantioselectivities. The ketone hydroacylation did not exhibit a significant H/D kinetic isotope effect (KIE) with respect to the aldehyde C-H bond, indicating that C-H activation would not be involved in the rate-limiting step.
- Yang, Junfeng,Yoshikai, Naohiko
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supporting information
p. 16748 - 16751
(2015/02/05)
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- Ene-carbonyl reductive coupling for the synthesis of 3,3-disubstituted phthalide, 3-hydroxyisoindolin-1-one and 3-hydroxyoxindole derivatives
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An efficient method for the synthesis of three classes of heterocyclic derivatives such as 3,3-disubstituted phthalides, 3-hydroxyisoindolin-1-ones and 3-hydroxyoxindoles, is reported. In the presence of the simple reductive system, zinc (Zn)/ammonia (NH3) [or zinc-copper (Zn-Cu)/ammonia], a wide range of alkenes including acrylates, acrylonitrile, acrylamide and vinyl sulfoxide underwent reductive coupling with methyl 2-acylbenzoates and subsequent lactonization to provide 3,3-disubstituted phthalides in good to high yields at ambient temperature. In a similar manner, 3-hydroxyisoindolin-1-one and 3-hydroxyoxindole derivatives could also be easily prepared by direct reductive coupling of phthalimides and N-substituted isatins with activated alkenes, respectively. Application of this methodology towards the synthesis of 1-naphthol derivatives on a gram scale is also depicted. Furthermore, the intramolecular phthalimides-ene reductive coupling afforded the respective cyclization products with high diastereoselectivity.
- Yeh, Chien-Hung,Lin, Yi-Chuen,Mannathan, Subramaniyan,Hung, Kevin,Cheng, Chien-Hong
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supporting information
p. 831 - 842
(2014/04/03)
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- Dehydrogenative lactonization of diols in aqueous media catalyzed by a water-soluble iridium complex bearing a functional bipyridine ligand
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A new catalytic system for the dehydrogenative lactonization of a variety of benzylic and aliphatic diols in aqueous media was developed. By using a water-soluble, dicationic iridium catalyst bearing 6,6′-dihydroxy-2, 2′-bipyridine as a functional ligand, highly atom economical and environmentally benign synthesis of various lactones was achieved in good to excellent yields. Recovery and reuse of the catalyst were also accomplished by a simple phase separation and the recovered catalyst maintained its high activity at least until the fifth run. Copyright
- Fujita, Ken-Ichi,Ito, Wataru,Yamaguchi, Ryohei
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p. 109 - 112
(2014/01/23)
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- Diastereomeric aziridine carbinol catalyzed enantioselective arylation reaction: Toward the asymmetric synthesis of both enantiomers of chiral 3-aryl phthalide
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The diastereomeric aziridine carbinols are applied, respectively, as efficient chiral ligand in the catalysis of asymmetric arylation and sequential arylation-lactonization cascade. The two diastereomers, which are facilely synthesized from the same chiral source, function as pseudo enantiomers in arylation of aromatic aldehydes providing the different enantiomers of the diarylmethanols with almost the same excellent enantioselectivities. The arylation method is also carried out in tandem with lactonization process to afford a concise synthetic approach to both enantiomers of optically active 3-aryl phthalide.
- Song, Xixi,Hua, Yuan-Zhao,Shi, Jing-Guo,Sun, Ping-Ping,Wang, Min-Can,Chang, Junbiao
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p. 6087 - 6093
(2014/07/21)
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- Gold-catalyzed formal cycloaddition of 2-ethynylbenzyl ethers with organic oxides and α-diazoesters
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A world of possibilities: Gold-catalyzed reactions of 2-ethynylbenzyl ethers with organic oxides and α-diazoesters gave 1,3-dihydroisobenzofuran and naphthalene derivatives, respectively (see scheme; EWG=electron-withdrawing group). Mechanisms for the formation of the formal cycloadducts were elucidated by isotope labeling. Copyright
- Pawar, Samir Kundlik,Wang, Chiou-Dong,Bhunia, Sabyasachi,Jadhav, Appaso Mahadev,Liu, Rai-Shung
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p. 7559 - 7563
(2013/07/26)
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- A One-pot preparation of 1,3-diarylisobenzofuran
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A simple, practical, and efficient method for one-pot synthesis of symmetric and unsymmetrical 1,3-diarylisobenzofurans has been developed by sequential reactions of methyl 2-formylbenzoate with two identical or different aryl metal species.
- Hamura, Toshiyuki,Nakayama, Ryosuke
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supporting information
p. 1013 - 1015
(2013/09/24)
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- Synthesis, characterization, and photoinduced CO-release reactivity of a Pb(II) flavonolate complex: Comparisons to Group 12 analogs
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The synthesis, characterization, and photoinduced CO-release reactivity of [(6-Ph2TPA)Pb(3-Hfl)]ClO4 (1; 6-Ph2TPA = N,N-bis((6-phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine; 3-Hfl = anion of 3-hydroxyflavone) is reported and compared with Group 12 analogues ([(6-Ph 2TPA)M(3-Hfl)]ClO4 (M = Hg(II) (2), Cd(II) (3), Zn(II) (4)). The Pb(II) complex exhibits unique features within this group of complexes in terms of its structural and spectroscopic features involving the coordinated flavonolate ligand. Similar to the Group 12 compounds, irradiation of 1 at 300 nm in an O2-containing environment results in the quantitative release of CO and the formation of a Pb(II) O-benzoylsalicylate (O-bs, depside) complex via a photoinduced dioxygenase-type reaction. Comparison of the quantum yield for the reaction of the Pb(II) flavonolate complex (Φ = 0.21(6)) versus the reactions of the structurally-related Group 12 metal complexes (6-Ph2TPA)M(3-Hfl)]ClO4 (M = Hg(II) (2, Φ = 0.31(2)), Cd(II) (3, Φ = 0.28(2)), Zn(II) (4), Φ = 0. 09(1)) revealed that flavonolate complexes of a heavy metal ion (Cd(II), Hg(II), Pb(II)) exhibit a higher reaction quantum yield than the Zn(II) derivative. Both Pb(II) and Zn(II) flavonolate complexes were found to be catalysts for the oxidative photoinduced degradation of 3-hydroxyflavone. The combined results of these investigations suggest that metal contaminants typically present in soil, including toxic heavy metal ions, might facilitate the oxidative decomposition of plant-derived flavonols via photoinduced reactions.
- Grubel, Katarzyna,Saraf, Sushma L.,Anderson, Stacey N.,Laughlin, Brynna J.,Smith, Rhett C.,Arif, Atta M.,Berreau, Lisa M.
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