- Dramatic Effect of γ-Heteroatom Dienolate Substituents on Counterion Assisted Asymmetric Anionic Amino-Cope Reaction Cascades
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We report a dramatic effect on product outcomes of the lithium ion enabled amino-Cope-like anionic asymmetric cascade when different γ-dienolate heteroatom substituents are employed. For dienolates with azide, thiomethyl, and trifluoromethylthiol substituents, a Mannich/amino-Cope/cyclization cascade ensues to form chiral cyclohexenone products with two new stereocenters in an anti-relationship. For fluoride-substituted nucleophiles, a Mannich/amino-Cope cascade proceeds to afford chiral acyclic products with two new stereocenters in a syn-relationship. Bromide- and chloride-substituted nucleophiles appear to proceed via the same pathway as the fluoride albeit with the added twist of a 3-exo-trig cyclization to yield chiral cyclopropane products with three stereocenters. When this same class of nucleophiles is substituted with a γ-nitro group, the Mannich-initiated cascade is now diverted to a β-lactam product instead of the amino-Cope pathway. These anionic asymmetric cascades are solvent- and counterion-dependent, with a lithium counterion being essential in combination with etheral solvents such as MTBE and CPME. By altering the geometry of the imine double bond from E to Z, the configurations at the R1 and X stereocenters are flipped. Mechanistic, computational, substituent, and counterion studies suggest that these cascades proceed via a common Mannich-product intermediate, which then proceeds via either a chair (X = N3, SMe, or SCF3) or boat-like (X = F, Cl, or Br) transition state to afford amino-Cope-like products or β-lactam in the case of X = NO2.
- Das, Pradipta,Delost, Michael D.,Qureshi, Munaum H.,Bao, Jianhua,Fell, Jason S.,Houk, Kendall N.,Njardarson, Jon T.
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supporting information
p. 5793 - 5804
(2021/05/07)
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- Cobalt-Catalyzed Diastereo- And Enantioselective Reductive Allyl Additions to Aldehydes with Allylic Alcohol Derivatives via Allyl Radical Intermediates
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Catalytic generation of ambiphilic π-allyl-metal complexes and their utility in enantioselective transformations constitutes a powerful approach for introduction of allyl groups to a molecule. Herein an unprecedented cobalt-catalyzed highly site-, diastereo-, and enantioselective protocol for stereoselective formation of nucleophilic allyl-Co(II) complexes followed by addition to aldehydes is presented. The reaction features diastereo- and enantioconvergent conversion of easily accessible allylic alcohol derivatives to diversified enantioenriched homoallylic alcohols with a remarkably broad scope of allyl groups that can be introduced. Mechanistic studies indicated that allyl radical intermediates were involved in this process. These new discoveries establish a new strategy for development of enantioselective transformations through capture of radicals by chiral Co complexes, pushing forward the frontier of Co complexes for enantioselective catalysis.
- Wang, Lei,Wang, Lifan,Li, Mingxia,Chong, Qinglei,Meng, Fanke
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supporting information
p. 12755 - 12765
(2021/08/30)
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- PROCESS FOR PREPARATION OF 4,4,4- TRIFLUOROBUT-2-EN-1-OL AND INTERMEDIATE THEREOF
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The present invention provides a process for preparation of 4,4,4- trifluorobut-2-en-1-ol from alkyl 4,4,4-trifluorobut-2-enoate and also provides one step process for preparation of alkyl 4,4,4-trifluorobut-2-enoate from corresponding hydroxy derivative using mild and easily available reagents.
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Page/Page column 12
(2020/07/31)
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- Copper-Catalyzed Asymmetric Defluoroborylation of 1-(Trifluoromethyl)Alkenes
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gem-Difluoroalkenes have steric and electronic profiles similar to those of ketones, aldehydes, and esters, and consequently have been used widely as carbonyl isosteres in modern drug discovery. Although many attempts have been made to achieve gem-difluor
- Gao, Pan,Yuan, Chengkai,Zhao, Yue,Shi, Zhuangzhi
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supporting information
p. 2201 - 2211
(2018/10/02)
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- A Copper(I)-Catalyzed Enantioselective γ-Boryl Substitution of Trifluoromethyl-Substituted Alkenes: Synthesis of Enantioenriched γ,γ-gem-Difluoroallylboronates
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The first catalytic enantioselective γ-boryl substitution of CF3-substituted alkenes is reported. A series of CF3-substituted alkenes was treated with a diboron reagent in the presence of a copper(I)/Josiphos catalyst to afford the c
- Kojima, Ryoto,Akiyama, Sota,Ito, Hajime
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supporting information
p. 7196 - 7199
(2018/06/15)
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- Introduction of the 4,4,4-Trifluorobut-2-ene Chain Exploiting a Regioselective Tsuji-Trost Reaction Catalyzed by Palladium Nanoparticles
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A palladium-nanoparticle-catalyzed Tsuji-Trost reaction of 4,4,4-trifluorobut-2-en-1-yl acetate and ethyl(4,4,4-trifluorobut-2-en-1-yl)carbonate was accomplished with various nucleophiles including phenols, amines, and malonates. In the case of the phenols, isomerization of the double bond in the product (up to 20%) was observed as a side reaction. Further synthetic transformations including hydrogenation, the Diels-Alder reaction, and asymmetric dihydroxylation of a product were also examined.
- Hemelaere, Rémy,Desroches, Justine,Paquin, Jean-Fran?ois
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supporting information
p. 1770 - 1773
(2015/04/14)
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- Systematic study of the reactivity of (E)-4,4,4-trifluorobut-2-en-1-yl 4-methylbenzenesulfonate towards different classes of nucleophiles
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A systematic study of the reactivity of (E)-4,4,4-trifluorobut-2-en-1-yl 4-methylbenzenesulfonate towards different classes of nucleophiles (alcohols, amines, thiols and malonates) was performed. A single set of reaction conditions (with small variations) allowed the isolation of the substitution product in moderate to good yields for all the nucleophiles tested with the exception of benzyl alcohol and indole.
- Forcellini, Elsa,Hemelaere, Rémy,Desroches, Justine,Paquin, Jean-Fran?ois
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p. 216 - 221
(2015/11/02)
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- Practical synthesis of 4,4,4-trifluorocrotonaldehyde: A versatile precursor for the enantioselective formation of trifluoromethylated stereogenic centers via organocatalytic 1,4-additions
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The practical synthesis of 4,4,4-trifluorocrotonaldehyde (1) and its application to enantioselective 1,4-additions are described. The organocatalytic 1,4-addition of 1 with several nucleophiles such as heteroaromatics, alkylthiols and aldoximes afforded t
- Shibatomi, Kazutaka,Narayama, Akira,Abe, Yoshiyuki,Iwasa, Seiji
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experimental part
p. 7380 - 7382
(2012/10/08)
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- Synthesis and cytotoxic activity of fluorinated analogues of Goniothalamus lactones. Impact of fluorine on oxidative processes
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Novel fluorinated analogues of goniothalamin 1 and howiinol A 2 have been prepared from trifluorocrotonate derivatives. Trifluoromethyl goniothalamin (R/S) 4 showed a slightly lower activity than 1, while the trifluoromethyl howiinol A 16 exhibited similar activities on several cell lines in the micromolar range. Unlike (R) goniothalamin and howiinol A, trifluoromethyl parent compounds remained unchanged when submitted to biomimetic oxidative systems.
- Dumitrescu, Lidia,Huong, Doan Thi Mai,Hung, Nguyen Van,Crousse, Benoit,Bonnet-Delpon, Danièle
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experimental part
p. 3213 - 3218
(2010/08/20)
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- 4-SUBSTITUTED PYRR0LIDIN-2-0NES AND THEIR USE
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The present invention relates to optically enriched or substantially optically pure 4-substituted-pyrrolidin-2-ones of formula (III), and their uses for the synthesis of 2-oxo-pyrrolidin-l-yl derivatives.
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Page/Page column 24
(2010/11/26)
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- Synthesis of trifluoromethylated analogues of β-l-fucofuranose and β-l-4,6-dideoxyxylohexopyranose
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Efficient strategy to trifluoromethylated trans-disubstituted alkene 3 was developed starting from commercially available 4,4,4-trifluoro-3-oxo-butyric acid ethyl ester 12. 6-Deoxy-6,6,6-trifluorosugars 21 and 30 were synthesized from 3 in high stereoselectivity and in a straightforward fashion. The key steps were Sharpless AD reaction, regioselective ring opening of trifluoromethylated cyclic sulfate, Horner-Wadsworth-Emmons reaction and TEMPO oxidation. It was noteworthy that the oxidation of alcohols 20 and 29 followed by deprotection and acetylation gave the single isomer target molecules 21 and 30, respectively.
- Wang, Bing-Lin,Yu, Fei,Qiu, Xiao-Long,Jiang, Zhong-Xing,Qing, Feng-Ling
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p. 580 - 587
(2008/03/14)
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- PROCESS FOR PREPARING 2-OXO-1-PYRROLIDINE DERIVATIVES BY INTRAMOLECULAR ALLYLATION
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The present invention relates to a new process for preparing 2-oxo-1-pyrrolidine derivatives of general formula (I), comprising the cyclisation of an intermediate of general formula (II) wherein the substituents are as defined in the specification.
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Page/Page column 12
(2008/06/13)
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- Asymmetric synthesis of both enantiomers of anti-4,4,4-trifluorothreonine and 2-amino-4,4,4-trifluorobutanoic acid
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A short and efficient enantio selective synthesis of both enantiomers of anti-4,4,4-trifluorothreonine and 2-amino-4,4,4-trifluorobutanoic acid was successfully developed. Trifluoromethylation of benzyl-protected bromoalkene 4 provided key intermediate trifluoromethylated transdi-substituted alkene 2 in good yield. The sequence then involved Sharpless asymmetric dihydroxylation, nucleophilic opening of cyclic sulfate with NaN3, palladium-catalyzed selective hydrogenation, and oxidation.
- Jiang, Zhong-Xing,Qin, Ying-Ying,Qing, Feng-Ling
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p. 7544 - 7547
(2007/10/03)
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- Tin- and indium-mediated allylation reactions in water: Highly stereoselective synthesis of β-trifluoromethylated homoallylic alcohols
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The indium-mediated allylation reaction of aldehydes with 4-bromo- 1,1,1-trifluoro-2-butene in water afforded β-trifluoromethylated homoallylic alcohols in high yields. In most cases, high regio- and excellent diastereoselectivities were obtained.
- Loh, Teck-Peng,Li, Xu-Ran
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p. 1893 - 1899
(2007/10/03)
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- N-Alkenyl Nitrone Dipolar Cycloaddition Routes to Piperidines and Indolizines. Part 6. Allylic Stereocontrol in the Intramolecular Cyclisation of Monosubstituted Nitrones
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The intarmolecular, thermal dipolar cycloadditions of the (Z)-N-alk-4-enyl nitrones 18-21, 34 and 36 bearing a single, allylic substituent were investigated.Certain alkoxy substituted nitrones 18-21 showed a remarkable preference for the formation of axially substituted isoxazolidines 22a-24a, whereas the propyl and trifluoromethyl substituted nitrones 35 and 34 gave the equatorially substituted cycloadducts 37 and 36a respectively, consistent with the involvement of 'chair-like' transition states 38.
- Collins, Ian,Nadin, Alan,Holmes, Andrew B.,Long, Martin E.,Man, Jocelyn,Baker, Raymond
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p. 2205 - 2216
(2007/10/02)
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- Ultrasound-Promoted Selective Perfluoroalkylation on the Desired Position of Organic Molecules
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Perfluoroalkylzinc iodides or bromides wich were prepared from perfluoroalkyl iodides or bromides and zinc powder in N,N-dimethylformamide or tetrahydrofuran with ultrasonic irradiation were found to behave as potential perfluoroalkylating reagents for the preparation of a wide variety of perfluoroalkylated compounds.Especially, the ultrasound-promoted asymmetric induction with perfluoroalkyl group on the asymmetrical carbon was achieved by the reaction of perfluoroalkyl halides with optically active enamines in the presence of zinc powder and a catalytic amount of dichlorobis(?-cyclopentadienyl)titanium.
- Kitazume, Tomoya,Ishikawa, Nobuo
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p. 5186 - 5191
(2007/10/02)
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- PREPARATION OF TRIFLUOROMETHYLATED ALLYLIC ALCOHOLS FROM TRIFLUOROACETALDEHYDE AND ORGANOMETALLIC COMPOUNDS
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A number of allylic alcohols bearing a trifluoromethyl group at the α- or γ-position, and α-trifluoromethylated γ-enols and -ynols were prepared by the reaction of trifluoroacetaldehyde with a variety of organometallic compounds.Most of the Reformatsky- or Grignard-type reactions required promotion by ultrasonic irradiation.
- Ishikawa, Nobuo,Koh, Moon Gyu,Kitazume, Tomoya,Choi, Sam Kwon
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p. 419 - 430
(2007/10/02)
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- ULTRASOUND-PROMOTED HYDRPERFLUOROALKYLATION OF ALKYNES WITH PERFLUOROALKYLZINC IODIDE AND COPPER(I) IODIDE
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The reaction of perfluoroalkyl iodides with terminal alkynes and ultrasonically dispersed zinc in the presence of copper(I) iodide proceeded smoothly to give the corresponding vinyl perfluoroalkylides in good yields.
- Kitazume, Tomoya,Ishikawa, Nobuo
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p. 1453 - 1454
(2007/10/02)
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