- A simple and efficient new approach to the total synthesis of (±)-4- amino-3-(4-chlorophenyl)-butyric acid (BACLOFEN)
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Based on the utilization of a [2+21 cycloaddition reaction between dichloroketene and an appropriated olefin as a key step, we describe a new and simple four step approach to the total synthesis of (±)-4-amino-3-(4- chlorophenyl)-butyric acid (BACLOFEN),
- Coelho, Fernando,De Azevedo, Mariangela B. M.,Boschiero, Roberta,Resende, Patricia
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- Copper-Catalyzed Sulfonylation of Cyclobutanone Oxime Esters with Sulfonyl Hydrazides
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A copper-catalyzed radical cross-coupling of cyclobutanone oxime esters with sulfonyl hydrazides has been developed. The copper-based catalytic system proved crucial for cleavage of the C-C bond of cyclobutanone oximes and for selective C-S bond-formation involving persistent sulfonyl-metal radical intermediates. This protocol is distinguished by the low-cost catalytic system, which does not require ligand, base, or toxic cyanide salt, and by the use of readily accessible starting materials, as well as broad substrate scope, providing an efficient approach to various diversely substituted cyano-containing sulfones.
- Dong, Bingbing,Lu, Jiansha,Bao, Honghao,Zhang, Yuanyuan,Liu, Yingguo,Leng, Yuting
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p. 3769 - 3776
(2021/07/14)
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- Desymmetrization of Prochiral Cyclobutanones via Nitrogen Insertion: A Concise Route to Chiral γ-Lactams
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Asymmetric access to γ-lactams is achieved via a cyclobutanone ring expansion using widely available (1S,2R)-1-amino-2-indanol for chiral induction. Mechanistic analysis of the key N,O-ketal rearrangement reveals a Curtin–Hammett scenario, which enables a downstream stereoinduction (up to 88:12 dr) and is corroborated by spectroscopic, crystallographic, and computational studies. In combination with an easy deprotection protocol, this operationally simple sequence allows the synthesis of a range of optically pure γ-lactams, including those bearing all-carbon quaternary stereocenters. In addition, the formal synthesis of drug molecules baclofen, brivaracetam, and pregabalin further demonstrates the synthetic utility and highlights the general applicability of the presented method.
- Sietmann, Jan,Ong, Mike,Mück-Lichtenfeld, Christian,Daniliuc, Constantin G.,Wiest, Johannes M.
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supporting information
p. 9719 - 9723
(2021/03/16)
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- Manganese=Catalyzed Achmatowicz Rearrangement Using Green Oxidant H2O2
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Oxidation reactions have been extensively studied in the context of the transformations of biomass=derived furans. However, in contrast to the vast literature on utilizing the stoichiometric oxidants, such as m=CPBA and NBS, catalytic methods for the oxidative furan=recyclizations remain scarcely investigated. Given this, we report a means of manganese=catalyzed oxidations of furan with low loading, achieving the Achmatowicz rearrangement in the presence of hydrogen peroxide as an environmentally benign oxidant under mild conditions with wide functional group compatibility.
- Gao, Ziwei,Gou, Jing,Hao, Zhe,Hou, Jing,Li, Chaoqun,Li, Gaoqiang,Xing, Qingzhao,Yu, Binxun
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p. 9563 - 9586
(2021/07/20)
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- CARBOXAMIDE AND SULFONAMIDE DERIVATIVES USEFUL AS TEAD MODULATORS
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The invention is concerned with the compounds of formula (I) and formula (II): and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of using the compounds of formula (I) and formula (II) as well as pharmaceutical compositions containing such compounds. The compounds are useful in treating diseases and conditions mediated by TEAD, such as cancer.
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Paragraph 0413-0417
(2020/03/29)
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- Photoinduced, Copper-Catalyzed Three-Component Annulation of gem-Dialkylthio Enynes
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Photoinduced, copper-catalyzed three-component radical annulation of gem-dialkylthio enynes, cyclobutanone oxime esters, and boronic acids was achieved, forming highly functionalized aryl thienyl sulfides with both good chemo- and diastereoselectivities. The reaction proceeds through a domino sequence involving cyanoalkyl radical-mediated intramolecular annulation of gem-dialkylthio enyne, alkenyl radical-promoted C(sp3)-S bond cleavage, and sulfur-centered radical-trapped Cu(II)-facilitated C-S cross-coupling. The protocol features simultaneous establishment of cyanoalkyl, cyclopentanone, and thiophene moieties and a thioether C-S bond in one pot with broad substrate scopes and versatile functional group tolerance under mild conditions.
- Lou, Jiang,Ma, Juan,Xu, Bao-Hua,Zhou, Yong-Gui,Yu, Zhengkun
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p. 5202 - 5206
(2020/07/15)
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- Copper-catalyzed ring-opening C(sp3)-N coupling of cycloketone oxime esters: Access to 1°, 2° and 3° alkyl amines
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A novel copper-catalyzed C(sp3)-N coupling of cycloketone oxime esters with nitrogen nucleophiles has been realized. All of the N-aryl/alkylanilines, anilines and benzophenone imine could be employed in this protocol to produce a variety of 1°, 2° and 3° alkyl amines in one or two steps. These resultant cyano-containing alkyl amines were proven to be versatile synthetic building blocks in a variety of chemical transformations.
- Tian, Li,Gao, Shuangqiu,Wang, Rui,Li, Yang,Tang, Chunlin,Shi, Lili,Fu, Junkai
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p. 5347 - 5350
(2019/05/10)
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- Transition-Metal-Promoted Direct C?H Cyanoalkylation and Cyanoalkoxylation of Internal Alkenes via Radical C?C Bond Cleavage of Cycloketone Oxime Esters
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Transition-metal-catalyzed alkyl-Heck-type cross-coupling of olefinic C?H bonds has been a challenge in the C?H activation area. Herein, we report FeCl3-promoted efficient direct C?H cyanoalkylation of internal alkenes, that is, ketene dithioacetals, with cycloketone oxime esters via radical C?C bond cleavage under the redox-neutral conditions. With CuCl2 as the catalyst under a dioxygen atmosphere direct C?H cyanoalkoxylation of the same internal alkenes was achieved. The cyanoalkylated tetrasubstituted alkene products could be diversely transformed to cyanoalkyl-funtionalized N- and S-heterocyclic compounds. The mechanistic studies have revealed that these C?H cyanoalkylation and cyanoalkoxylation reactions proceed through a radical pathway. (Figure presented.).
- Lou, Jiang,He, Yuan,Li, Yunlong,Yu, Zhengkun
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p. 3787 - 3799
(2019/07/10)
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- Synthesis and Physicochemical Properties of 3-Fluorocyclobutylamines
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Hitherto unknown cis- and trans-3-alkyl- and 3-aryl-3-fluorocycobutylamines have been synthesised selectively from 3-oxocyclobutane carboxylic acid in six or seven steps. Comparison of their pKa and logD values with those of the fluorine-free p
- Chernykh, Anton V.,Radchenko, Dmytro S.,Chernykh, Alla V.,Kondratov, Ivan S.,Tolmachova, Nataliya A.,Datsenko, Olexandr P.,Kurkunov, Maxim A.,Zozulya, Sergey X.,Kheylik, Yuri P.,Bartels, Katharina,Daniliuc, Constantin G.,Haufe, Günter
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supporting information
p. 6466 - 6471
(2015/10/19)
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- Baeyer-Villiger Oxidation of Cyclobutanones with 10-Methylacridinium as an Efficient Organocatalyst
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Baeyer-Villiger oxidation of cyclobutanones is achieved in current developed protocol with 10-methylacridinium perchlorate (AcrH +ClO4-) as a novel organocatalyst both with irradiation at room temperature and without irradiation at elevated temperature. Excellent yields of the corresponding lactones are obtained and the possible mechanism has been proposed.
- Xu, Hua-Jian,Zhu, Feng-Fei,Shen, Yong-Ya,Wan, Xin,Feng, Yi-Si
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p. 4145 - 4151
(2012/07/27)
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- Enantioselective baeyer-villiger oxidation: Desymmetrization of meso cyclic ketones and kinetic resolution of racemic 2-arylcyclohexanones
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Catalytic enantioselective Baeyer-Villiger (BV) oxidations of racemic and meso cyclic ketones were achieved in the presence of chiral N,N'-dioxide-Sc III complex catalysts. The BV oxidations of prochiral cyclohexanones and cyclobutanones afforded series of optically active μ- and γ-lactones, respectively, in up to 99% yield and 95% ee. Meanwhile, the kinetic resolution of racemic 2-arylcyclohexanones was also realized via an abnormal BV oxidation. Enantioenriched 3-aryloxepan-2-ones, whose formation is counter to the migratory aptitude, were obtained preferentially. Both the lactones and the unreacted ketones were obtained with high ee values.
- Zhou, Lin,Liu, Xiaohua,Ji, Jie,Zhang, Yuheng,Hu, Xiaolei,Lin, Lili,Feng, Xiaoming
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p. 17023 - 17026,4
(2012/12/12)
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- Enantioselective baeyer-villiger oxidation: Desymmetrization of meso cyclic ketones and kinetic resolution of racemic 2-arylcyclohexanones
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Catalytic enantioselective Baeyer-Villiger (BV) oxidations of racemic and meso cyclic ketones were achieved in the presence of chiral N,N'-dioxide-Sc III complex catalysts. The BV oxidations of prochiral cyclohexanones and cyclobutanones afforded series of optically active μ- and γ-lactones, respectively, in up to 99% yield and 95% ee. Meanwhile, the kinetic resolution of racemic 2-arylcyclohexanones was also realized via an abnormal BV oxidation. Enantioenriched 3-aryloxepan-2-ones, whose formation is counter to the migratory aptitude, were obtained preferentially. Both the lactones and the unreacted ketones were obtained with high ee values.
- Zhou, Lin,Liu, Xiaohua,Ji, Jie,Zhang, Yuheng,Hu, Xiaolei,Lin, Lili,Feng, Xiaoming
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p. 17023 - 17026
(2013/01/15)
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- Palladium-catalyzed, asymmetric Baeyer-Villiger oxidation of prochiral cyclobutanones with PHOX ligands
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Described in this report is a general method for the conversion of prochiral 3-substituted cyclobutanones to enantioenriched γ-lactones through a palladium-catalyzed Baeyer-Villiger oxidation using phosphinooxazoline ligands in up to 99% yield and 81% ee. Lactones of enantiopurity ≥93% could be obtained through a single recrystallization step. Importantly, 3,3-disubtituted cyclobutanones produced enantioenriched lactones containing a β-quaternary center.
- Petersen, Kimberly S.,Stoltz, Brian M.
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p. 4352 - 4357
(2011/07/29)
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- SUBSTITUTED HETEROCYCLIC DERIVATIVES AND THEIR PHARMACEUTICAL USE AND COMPOSITIONS
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Compounds of the general Formula I, wherein X1, X2, X3, X4, X5, X6, X7, R1, R2, R4, R5, R6, R7, R8, R9, R10, Y1, n, m, p and q are defined as above, their preparation and their use as antimicrobial agents.
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Page/Page column 18
(2008/12/08)
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- Enantioselective baeyer-villiger oxidation catalyzed by palladium(II) complexes with chiral P,N-ligands
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(Chemical Equation Presented) Asymmetric Baeyer-Villiger reaction of symmetrical cyclobutanones 1a-j with urea-hydrogen peroxide (UHP) can be catalyzed by a complex of Pd(II) and the new terpene-derived P,N-ligand 7. The resulting lactones 2a-j were obtained in high yields and with good enantioselectivity (≤81% ee).
- Malkov, Andrei V.,Friscourt, Frederic,Bell, Mark,Swarbrick, Martin E.,Kocovsky, Pavel
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p. 3996 - 4003
(2008/09/20)
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- Comparing the stereoselective biooxidation of cyclobutanones by recombinant strains expressing bacterial baeyer - Villiger monooxygenases
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Microbial Baeyer - Villiger oxidation of representative prochiral ketones with a cyclobutanone structural motif was investigated using a collection of eight monooxygenases of different bacterial origin. This platform of enzymes is able to perform stereoselective biotransformations on an array of structurally diverse substrates. With several ketone precursors, biooxidations yielded enantiocomplementary butyrolactones as key intermediates for the synthesis of natural products and bioactive compounds. The microbial Baeyer - Villiger oxidation allows a facile and rapid entry to several compound classes in a desymmetrization reaction upon de novo generation of chirality.
- Rudroff, Florian,Rydz, Joanna,Ogink, Freek H.,Fink, Michael,Mihovilovic, Marko D.
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p. 1436 - 1444
(2008/09/17)
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- An efficient synthesis of (R)-(-)-baclofen
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In this report we describe an efficient synthesis of (R)-(-)-baclofen, a selective GABA(B) agonist used as an antispastic agent. Our strategy is based on an enantioselective deprotonation of a cyclobutanone easily obtained by [2+2] cycloaddition of 4-chlorostyrene and dichloroketene.
- Resende, Patricia,Almeida, Wanda P.,Coelho, Fernando
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p. 2113 - 2118
(2007/10/03)
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- A chemoenzymatic strategy for the synthesis of enantiopure (R)-(-)-baclofen
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A seven-step enantioselective synthesis of (R)-(-)-baclofen 1 is described. The strategy developed involved as a key step, a microbiologically mediated Baeyer Villiger oxidation of the prochiral 3-(4'-chlorobenzyl)-cyclobutanone 3 which led to the optically pure (R)-(-)-4 lactone. This was further transformed throughout chemospecific reactions into the target molecule (R)-(-)-1.
- Mazzini, Claudio,Lebreton, Jacques,Alphand, Veronique,Furstoss, Roland
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p. 1195 - 1196
(2007/10/03)
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- Substituent effects on cyclobutyl and cyclopropylcarbinyl cations
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The acetolyses of 3-substituted cyclobutyl tosylates (X = Ar, Cl, and OEt) were examined giving rate constants and product distributions. With the alkyl- and aryl-substituted compounds, the rate-determining step leads to the formation of a bridged cyclobu
- Wiberg, Kenneth B.,Shobe, David,Nelson, Gordon L.
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p. 10645 - 10652
(2007/10/02)
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