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Jariya Sakayaroj - One of the best experts on this subject based on the ideXlab platform.
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amide cyclohexenone and cyclohexenone sordaricin derivatives from the endophytic fungus xylaria plebeja psu g30
ChemInform, 2014Co-Authors: Vatcharin Rukachaisirikul, Sathit Buadam, Souwalak Phongpaichit, Jariya SakayarojAbstract:Two new Cyclohexenones, named xylariacyclones A (Ia) and B (Ib), three cyclohexenone—sordaricin derivatives, named xylarinonericins A (IIa), B (IIb), and C (IIc), as well as xylariamide (III) are isolated along with 11 known compounds from the broth extract of the endophytic fungus Xylaria plebeja PSU-G30.
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amide cyclohexenone and cyclohexenone sordaricin derivatives from the endophytic fungus xylaria plebeja psu g30
Tetrahedron, 2013Co-Authors: Vatcharin Rukachaisirikul, Sathit Buadam, Souwalak Phongpaichit, Jariya SakayarojAbstract:Abstract Six new compounds, two Cyclohexenones, named xylariacyclones A (1) and B (2), three cyclohexenone–sordaricin derivatives, named xylarinonericins A–C (3–5), and one amide derivative, named xylariamide (6), together with 11 known compounds were isolated from the broth extract of the endophytic fungus Xylaria plebeja PSU-G30. The structures were elucidated by analyses of NMR spectroscopic data and chemical methods. Compounds 3–5 are novel and unusual sodaricin derivatives with an ester moiety at C-6 of the sordaricin skeleton. In addition, compound 5 has a unique feature with an ester unit instead of an ether group at C-19. They were evaluated for antifungal activity against Candida albicans ATCC90028 and Cryptococcus neoformans ATCC90113.
Fumie Sato - One of the best experts on this subject based on the ideXlab platform.
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synthesis of optically active 5 tert butyldimethylsiloxy 2 cyclohexenone and its 6 substituted derivatives as useful chiral building blocks for the synthesis of cyclohexane rings syntheses of carvone penienone and penihydrone
Journal of the American Chemical Society, 1999Co-Authors: Georges P.‐j. Hareau, Shinichi Hikichi, Masakazu Koiwa, Fumie SatoAbstract:Optically active 5-(tert-butyldimethylsiloxy)-2-cyclohexenone (1) and its 6-substituted derivatives 2a,b were synthesized from the readily available optically active ethyl 3-(tert-butyldimethylsiloxy)-5-hexenoate (4), where the Ti(II)-mediated intramolecular nucleophilic acyl substitution reaction and the FeCl3-mediated ring expansion reaction of a 1-hydroxybicyclo[3.1.0]hexane are the key reactions. The enone 1 reacted with higher-order cyanocuprates with excellent diastereoselectivity to afford the trans-addition products, trans-13, in excellent yields. The reaction of 1 with lower-order cyanocuprates proceeded with moderate to excellent syn-selectivity to afford cis-13. Treatment of trans- and cis-13 with DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) or catalyst p-TSA (p-toluenesulfonic acid) resulted in a β-elimination reaction to furnish the corresponding optically active 5-substituted-2-Cyclohexenones 14. The 1,4-addition reaction of 2a and 2b with organocyanocuprates followed by treatment of the resulti...
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unexpected cis selective 1 4 addition reaction of lower order cyanocuprates to optically active 5 tert butyldimethylsiloxy 2 cyclohexenone
Angewandte Chemie, 1998Co-Authors: Georges Hareauvittini, Shinichi Hikichi, Fumie SatoAbstract:: A remarkable cis selectivity has been observed in the 1,4-addition of lower order primary and secondary alkylcyanocuprates to 5-silyloxy- and 5-benzyloxy-substituted Cyclohexenones. This enables the preparation of both enantiomers of the corresponding 5-alkyl-substituted Cyclohexenones (S)- and (R)-3 by the reaction of the readily available 5-(tert-butyldimethylsiloxy)-2-cyclohexenone (1) with either the lower or higher order cyanocuprate. DBU=1,8-diazabicyclo[5.4.0]undec-7-ene.
Kiyoshi Tomioka - One of the best experts on this subject based on the ideXlab platform.
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amidophosphane copper i catalyzed asymmetric conjugate addition of dialkylzinc reagents to racemic 6 substituted Cyclohexenones to form 2 5 di and 2 2 5 trisubstituted cyclohexanones
Chemistry-an Asian Journal, 2008Co-Authors: Khalid B Selim, Takahiro Soeta, Kenichi Yamada, Kiyoshi TomiokaAbstract:The asymmetric conjugate addition of dialkylzinc reagents to racemic 6-substituted Cyclohexenones under the catalysis of chiral amidophosphane-copper(I) complexes gave a mixture of nearly equal amounts of the corresponding trans- and cis-disubstituted cyclohexanones with extremely high catalyst-controlled enantioselectivity. Epimerization with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) led to the conversion of these mixtures into the thermodynamically more stable trans-2,5-disubstituted cyclohexanone as the major product with up to 96% ee in up to 96% yield. The regio- and stereoselective alkylation of the disubstituted cyclohexanone products via the thermodynamically favored enolate gave 2,2,5-trisubstituted cyclohexanones with a quaternary asymmetric carbon atom in good yield.
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efficient catalytic asymmetric synthesis of trans 5 aryl 2 substituted cyclohexanones by rhodium catalyzed conjugate arylation of racemic 6 substituted Cyclohexenones
Advanced Synthesis & Catalysis, 2006Co-Authors: Qian Chen, Takahiro Soeta, Kenichi Yamada, Masami Kuriyama, Kiyoshi TomiokaAbstract:Catalytic asymmetric conjugate arylation of racemic 6-substituted Cyclohexenones with arylboronic acids was catalyzed by 3 mol % of chiral amidophosphane-[RhCl(C2H4)]2 in a 10:1 mixture of 1,4-dioxane and water at 70 °C to afford a nearly 1:1 mixture of trans- and cis-5-aryl-2-substituted cyclohexanones in high enantioselectivity, which was subsequently epimerized with sodium ethoxide in ethanol to give thermodynamically stable trans-5-aryl-2-substituted cyclohexanones with 99–97 % ee in high two-step yields.
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asymmetric synthesis of 5 arylCyclohexenones by rhodium i catalyzed conjugate arylation of racemic 5 trimethylsilyl cyclohexenone with arylboronic acids
Organic Letters, 2005Co-Authors: Qian Chen, Masami Kuriyama, Takahiro Soeta, Kenichi Yamada, Kiyoshi TomiokaAbstract:A catalytic asymmetric conjugate arylation of racemic 5-(trimethylsilyl)cyclohex-2-enone with arylboronic acids was catalyzed by 3 mol % chiral amidophosphane- or BINAP-Rh(I) in dioxane−water (10:1) to afford trans- and cis-3-aryl-5-(trimethylsilyl)cyclohexanones in high enantioselectivity. Dehydrosilylation of the product mixture with cupric chloride in DMF gave 5-arylcyclohex-2-enones with up to 93% ee in good yield. Enantiofacial selectivity with chiral phosphane-Rh(I) exceeds the trans-diastereoselectivity that is maintained in the achiral or racemic phosphane-Rh(I)-catalyzed conjugate arylation of 5-(trimethylsilyl)cyclohexenone.
Makoto Tokunaga - One of the best experts on this subject based on the ideXlab platform.
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aerobic oxidation of cyclohexanones to phenols and aryl ethers over supported pd catalysts
Organic chemistry frontiers, 2015Co-Authors: Zhenzhong Zhang, Taishin Hashiguchi, Tamao Ishida, Akiyuki Hamasaki, Tetsuo Honma, Hironori Ohashi, Takushi Yokoyama, Makoto TokunagaAbstract:Transformation of cyclohexanones to phenols and aryl ethers over supported Pd catalysts using molecular oxygen as the sole oxidant is developed. Several metal oxide supported Pd catalysts were used to activate the C–H bond in cyclohexanones to produce Cyclohexenones and phenols through oxidation. Although the selectivity of Cyclohexenones was difficult to control, phenols were obtained in excellent yield with a broad substrate scope. A novel catalytic system, using ZrO2 supported Pd(OH)2, was proposed for the synthesis of aryl ethers, and the products were obtained in moderate to excellent yields. Orthoesters, such as trimethyl orthoformate (TMOF), triethyl orthoformate (TEOF), and triisopropyl orthoformate (TIPOF), enabled nucleophilic addition and elimination after activation of cyclohexanones over a Pd catalyst to produce the corresponding aryl ethers. TIPOF was also used as the dehydrating reagent to promote the reaction of cyclohexanones with alcohols for the preparation of versatile aryl ethers.
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palladium catalyzed oxidation of cyclohexanones to conjugated enones using molecular oxygen
Tetrahedron Letters, 2007Co-Authors: Makoto Tokunaga, Saki Harada, Tetsuo Iwasawa, Yasushi Obora, Yasushi TsujiAbstract:Abstract Oxidation of cyclohexanones into conjugated enones with molecular oxygen as oxidant was achieved by palladium catalysts. A catalyst system consists of 1 mol % Pd(OCOCF3)2 and 5,5′-dimethyl-2,2′-bipyridine accomplished maximum 84% yield for the oxidation of cyclohexanone and 51–78% yields for 4-substituted-cyclohexanones.
Shannon S Stahl - One of the best experts on this subject based on the ideXlab platform.
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aerobic dehydrogenation of cyclohexanone to cyclohexenone catalyzed by pd dmso 2 tfa 2 evidence for ligand controlled chemoselectivity
Journal of the American Chemical Society, 2013Co-Authors: Tianning Diao, Shannon S StahlAbstract:The dehydrogenation of cyclohexanones affords Cyclohexenones or phenols via removal of 1 or 2 equiv of H2, respectively. We recently reported several PdII catalyst systems that effect aerobic dehydrogenation of cyclohexanones with different product selectivities. Pd(DMSO)2(TFA)2 is unique in its high chemoselectivity for the conversion of cyclohexanones to Cyclohexenones, without promoting subsequent dehydrogenation of Cyclohexenones to phenols. Kinetic and mechanistic studies of these reactions reveal the key role of the dimethylsulfoxide (DMSO) ligand in controlling this chemoselectivity. DMSO has minimal kinetic influence on the rate of Pd(TFA)2-catalyzed dehydrogenation of cyclohexanone to cyclohexenone, while it strongly inhibits the second dehydrogenation step, conversion of cyclohexenone to phenol. These contrasting kinetic effects of DMSO provide the basis for chemoselective formation of Cyclohexenones.
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aerobic dehydrogenation of cyclohexanone to phenol catalyzed by pd tfa 2 2 dimethylaminopyridine evidence for the role of pd nanoparticles
Journal of the American Chemical Society, 2013Co-Authors: Doris Pun, Tianning Diao, Shannon S StahlAbstract:We have carried out a mechanistic investigation of aerobic dehydrogenation of cyclohexanones and Cyclohexenones to phenols with a Pd(TFA)2/2-dimethylaminopyridine catalyst system. Numerous experimental methods, including kinetic studies, filtration tests, Hg poisoning experiments, transmission electron microscopy, and dynamic light scattering, provide compelling evidence that the initial PdII catalyst mediates the first dehydrogenation of cyclohexanone to cyclohexenone, after which it evolves into soluble Pd nanoparticles that retain catalytic activity. This nanoparticle formation and stabilization is facilitated by each of the components in the catalytic reaction, including the ligand, TsOH, DMSO, substrate, and cyclohexenone intermediate.
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aerobic oxidative heck dehydrogenation reactions of Cyclohexenones efficient access to meta substituted phenols
Angewandte Chemie, 2013Co-Authors: Yusuke Izawa, Changwu Zheng, Shannon S StahlAbstract:Phenol derivatives are common and important structural motifs in bioactive natural products and pharmaceuticals,[1] and the selective synthesis of substituted phenols is facilated by the strong ortho/para-directing effect of the hydroxyl group. The same directing effect, however, limits access to analogous meta-substituted derivatives. In recent years, considerable efforts have targeted C–H functionalization reactions that enable preparation of meta-substituted arenes via steric[2] or directing-group[3] control over the site selectivity. The overall efficiency of these methods is often limited by functional group interconversions or installation/removal of directing groups needed to access the final product.[4] Moreover, in molecules with more than one electronically or sterically active substituent, competition between the directing groups can lead to product mixtures. Following our recent development of Pd-catalyzed aerobic dehydrogenation reactions of ketones,[5,6,7] we envisioned that meta-substituted phenols could be accessed efficiently via an aerobic oxidative Heck/dehydrogenation sequence with cyclohexenone (Scheme 1).[8] Cyclohexenone is a convenient and inexpensive phenol precursor, and the proposed strategy exploits the intrinsic regioselectivity of additions to electron-deficient alkenes to enable functionalization of the "meta" C–H bond. Here, we describe a new Pd catalyst and reaction conditions compatible with this sequence, and we showcase their utility in the synthesis of a pharmaceutically active phenol derivative. Scheme 1 Strategy for the synthesis of meta-substituted phenols. The proposed sequence in Scheme 1 faces several challenges. The oxidative Heck reaction must be more facile than the dehydrogenation step in order to avoid direct conversion of the cyclohexenone starting material to unsubstituted phenol. Furthermore, while aerobic oxidative Heck reactions have extensive precedent with terminal alkenes,[9, 10] analogous reactions with cyclohexenone tend to be more difficult.[11,12] With this substrate, the PdII-enolate must isomerize to place the Pd atom on the opposite side of the ring in order to undergo β-hydride elimination (Scheme 2.[13] Finally, the catalyst and conditions must be compatible with both reactions in the sequence. The only general method for dehydrogenation of Cyclohexenones to phenols employs a strong-acid additive (p-TsOH; Scheme 3),[5a] which interferes with oxidative Heck reactions.[14] Scheme 2 Mechanistic steps highlighting the requirement for isomerization of the PdII-enolate intermediate in Heck reactions of cyclohexenone. Scheme 3 Previously reported aerobic dehydrogenation conditions for the synthesis of phenols. Our initial studies targeted the identification of non-acidic reaction conditions for aerobic dehydrogenation of 3-methylcyclohexenone. Upon screening diverse PdX2 sources, ligands, additives and solvents (see Supp. Info. for full screening data), we found that the dicationic PdII complex [Pd(CH3CN)4](BF4)2 was particularly effective as a catalyst (Table 1). Formation of Pd black and gradual loss of catalytic activity during the reaction prompted us to test ancillary ligands to stabilize the catalyst. Most of the ligands tested inhibited the reaction (cf. Table 1 and Supp. Info.); however, 4,5-diazafluorenone L4[15] and 6,6'-dimethyl-2,2'-bipyridine L5 enabled good product yields to be obtained. While screening of numerous additives, including Bronsted bases, CuII and AgI salts, and quinones showed little beneficial effect, nearly quantitative yield of the phenol product (95%) was obtained when 9 mol % AMS (anthraquinone-2-sulfonic acid sodium salt) was included in the reaction with ligand L5.[16] The optimal result was obtained upon addition of water (20 vol %) to enhance the solubility of AMS. Table 1 Dehydrogenation of 3-Cyclohexenones: Screening Results.[a] The optimized conditions proved to be effective with a number other substituted Cyclohexenones, including those with heteroatom substituents (Table 2). These neutral reaction conditions revealed some advantages over the previously reported conditions in Scheme 3. For example, 6-phenylcyclohexanone underwent dehydrogenation to o-phenyl phenol in only 33% yield under the previous conditions, but this product is obtained in excellent yields under the present conditions (entries 1 and 2). The successful reaction of 3-arylCyclohexenones, prepared via oxidative Heck reactions with cyclohexenone (entries 9–11), provided a useful starting point for the investigation of oxidative Heck and tandem oxidative Heck/dehydrogenation reactions. Table 2 Dehydrogenation of Substituted Cyclohexenones,[a] Preliminary experiments showed that this catalyst was quite effective for the oxidative Heck coupling of 4-methoxyphenylboronic acid and cyclohexenone. Moveover, the reaction could take place at 50 °C, a temperature at which no conversion of cyclohexenone to phenol was observed. In DMSO, the oxidative Heck reaction proceeded in 65% yield. Upon heating of this reaction mixture to 80 °C, nearly complete in situ conversion to the 3-aryl phenol was observed (i.e., 64% yield of the phenol; Table 3, entry 1). Several other solvents, including DMF, N-methylpyrrolidone (NMP) and 1,4-dioxane, proved to be better for the oxidative Heck reaction (entries 2–7); however, they proved less effective for the tandem sequence (e.g., entry 2). Further studies revealed that an effective one-pot sequence could be achieved by performing the oxidative Heck reaction in NMP at 50 °C, followed by addition of DMSO and heating to 80 °C for the dehydrogenation step. This protocol enabled a good yield of the phenol to be obtained (84%, entry 12). Table 3 Optimization of Conditions for the Oxidative Heck and one-pot Oxidative Heck/Dehydrogenation Reactions.[a] [Pd(CH3CN)4](BF4)2/L5 proved to be very effective as a standalone catalyst for oxidative Heck reactions with cyclohexenone. Good yields of the 3-arylCyclohexenones were obtained with diverse arylboronic acids (Table 4). Reactions with the electron-rich arylboronic acids typically led to higher yields than electron-deficient substrates as the latter substrates were more susceptible to the formation of homocoupling products. Halogenated arylboronic acids (X = F, Cl, Br) were tolerated in the oxidative Heck reaction, with yields ranging from 68% to 86% (entries 4–6 and 18). The same arylboronic acids were then employed in the one-pot oxidative Heck/dehydrogenation to afford the 3-substituted phenol derivatives. In most cases, the phenol yields correlate closely with the yields of the 3-aryl Cyclohexenones in the independent oxidative Heck reaction. Table 4 Oxidative Heck and One-Pot Oxidative Heck/Dehydrogenation Reactions to Prepare Substituted Cyclohexenones and Phenols.[a] In order to demonstrate the potential utility of the aerobic oxidative Heck/dehydrogenation sequence and further test its functional group compatibility, we investigated the synthesis of URB597 from cyclohexenone and the commercially available benzamide-derived boronic acid 1 (Scheme 4). URB597 is a potent inhibitor of fatty acid amide hydrolase (FAAH) and an important focus of efforts to treat pain, anxiety and depression.[17,18] The phenol intermediate 3 was prepared via stepwise oxidative Heck coupling of 1 and cyclohexenone, followed by catalytic dehydrogenation of the isolated intermediate 2, and in a direct, one-pot process. The [Pd(CH3CN)4](BF4)2/L5 catalyst was employed for each of these steps, and both pathways led to the phenol product 3 in good yield (approx. 72%, in each case). Scheme 4 Application of one-pot oxidative Heck/dehydrogenation reactions in the synthesis of URB597. The results above highlight a new catalyst system that mediates both aerobic oxidative Heck reactions with cyclohexenone and aerobic dehydrogenation of Cyclohexenones. The one-pot sequence developed for these reactions represents an efficient strategy for the preparation of meta substituted of phenols, which should be advantageous or highly competitive with other approaches based on C–H functionalization of an aromatic ring.
