- Aldol-Tishchenko Reaction of α-Oxy Ketones: Diastereoselective Synthesis of 1,2,3-Triol Derivatives
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α-Oxy ketones, easily accessible by conventional routes, can be selectively deprotonated generating an enolate intermediate, which upon treatment with paraformaldehyde undergoes an aldol-Tishchenko reaction, leading to relevant 1,2,3-triol fragments in a totally diastereoselective manner. The excellent stereocontrol in the generation of a quaternary stereocenter is attributed to stereoelectronic effects in the Evans intermediate. This methodology allows overcoming some limitations of our previously reported strategy, based on the reaction of α-lithiobenzyl ethers with esters and paraformaldehyde, broadening the scope of the obtained polyols. Synthetic applications of this process include the preparation of a new dilignol model and some functionalized oxetanes.
- Sedano, Carlos,Virumbrales, Cintia,Suárez-Pantiga, Samuel,Sanz, Roberto
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supporting information
p. 3725 - 3734
(2021/07/02)
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- Synthesis of α,β-dibromo ketones by photolysis of α-bromo ketones with N-bromosuccinimide: Photoinduced β-bromination of α-bromo ketones
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Irradiation of α-bromopropiophenones in the presence of NBS results in the formation of α,β-dibromopropiophenones, which can be viewed as β-bromination of α-bromopropiophenones. The reaction is believed to go through a series of reactions; photoinduced C–Br bond cleavage, elimination of HBr to give α,β-unsaturated ketone intermediates, and addition of Br2, which are formed by the reaction between HBr and NBS. From mechanistic studies of the reaction, we have also found a very convenient method for α-debromination of the α,β-dibromopropiophenones which is by simple irradiation of the dibromo ketones in acetone or 2-propanol without the use of any additives. Our results demonstrate that bromine can be added into or eliminated from the alpha, beta, or both positions to the carbonyl group by photochemical methods, which make synthetic options of bromine containing carbonyl compounds versatile.
- Moon, Da Yoon,An, Sejin,Park, Bong Ser
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- Solvent free, light induced 1,2-bromine shift reaction of α-bromo ketones
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Photolysis of α-bromopropiophenones in acetonitrile results in formation of β-bromopropiophenones with good product selectivity, which can be coined as 1,2-Br shift reaction. The product selectivity increases when the reaction is done in neat or solid state, where only the 1,2-Br shift product is formed in some cases. The reaction is suggested to proceed by C–Br bond homolysis to give a radical pair, followed by disproportionation and conjugate addition of HBr to the α,β-unsaturated ketone intermediate. When the unsaturated intermediate is stabilized by an extra conjugation, the reaction stops at the stage, in which the unsaturated ketone becomes a major product. The synthetic method described in this research fits in a category of eco-friendly organic synthesis nicely since the reaction does not use volatile organic solvents and any other additives such as acid, base or metal catalysts, etc. Besides, the method fits into perfect atom economy, which does not give any side products. The synthetic method should find much advantage over other alternative methods to obtain β-bromo carbonyl compounds.
- An, Sejin,Moon, Da Yoon,Park, Bong Ser
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p. 6922 - 6928
(2018/10/24)
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- Iodine(III)-Mediated Oxidative Hydrolysis of Haloalkenes: Investigation of the Effect of Iodine(III) Reagents
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The iodine(III)-mediated oxidative transposition of vinyl halides to the corresponding α-halo ketones has been recently reported. The method is high yielding and offers good substrate scope. The investigation of other iodine(III) reagents to promote this
- Dagenais, Robin,Lauriers, Antoine Jobin-Des,Legault, Claude Y.
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p. 2928 - 2932
(2017/06/27)
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- Unexpected Role of p-Toluenesulfonylmethyl Isocyanide as a Sulfonylating Agent in Reactions with α-Bromocarbonyl Compounds
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The reactions of p-toluenesulfonylmethyl isocyanide (TosMIC) with α-bromocarbonyl compounds leading efficiently to α-sulfonated ketones, esters, and amides were reported, in which an explicit new role of TosMIC as the sulfonylating agent was uncovered for the first time. Mechanistic study by control experiments and DFT calculations suggested that the reaction is initiated by Cu(OTf)2-catalyzed hydration of TosMIC to form a formamide intermediate, which undergoes facile C-S bond cleavage under the mediation of a Cs2CO3 additive.
- Chen, Jiajia,Guo, Wei,Wang, Zhenrong,Hu, Lin,Chen, Fan,Xia, Yuanzhi
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p. 5504 - 5512
(2016/07/13)
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- Iodine(III)-Mediated Oxidative Hydrolysis of Haloalkenes: Access to α-Halo Ketones by a Release-and-Catch Mechanism
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An unprecedented iodine(III)-mediated oxidative transposition of vinyl halides has been accomplished. The products obtained, α-halo ketones, are useful and polyvalent synthetic precursors. There are only a handful of reported examples of the direct conversion of vinyl halides to their corresponding α-halo carbonyl compounds. Insights into the mechanism and demonstration that this synthetic transformation can be done under enantioselective conditions are reported.
- Jobin-Des Lauriers, Antoine,Legault, Claude Y.
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supporting information
p. 108 - 111
(2016/01/15)
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- Copper-catalyzed 1,2-addition of α-carbonyl iodides to alkynes
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β,γ-Unsaturated ketones are an important class of organic molecules. Herein, copper catalysis has been developed for the synthesis of β-γ-unsaturated ketones through 1,2-addition of α-carbonyl iodides to alkynes. The reactions exhibit wide substrate scope and high functional group tolerance. The reaction products are versatile synthetic intermediates to complex small molecules. The method was applied for the formal synthesis of (±)-trichostatin A, a histone deacetylase inhibitor.
- Xu, Tao,Hu, Xile
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supporting information
p. 1307 - 1311
(2015/01/30)
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- Substituted 2-aminothiazoles are exceptional inhibitors of neuronal degeneration in tau-driven models of Alzheimer's disease
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A novel series of 2-aminothiazoles with strong protection in an Alzheimer's disease (AD) model comprising tau-induced neuronal toxicity is disclosed. These derivatives can be synthesized in one-pot and a small SAR of the substitution within these series afforded several compounds that counteracted tau-induced cell toxicity at nanomolar concentrations. These congeners therefore have strong potential as possible treatment for Alzheimer's disease and other related tauopathies.
- Lagoja, Irene,Pannecouque, Christophe,Griffioen, Gerard,Wera, Stefaan,Rojasdelaparra, Veronica Maria,Van Aerschot, Arthur
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experimental part
p. 386 - 392
(2012/05/31)
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- Acid-mediated cyclization of 3-benzoyl-2-cyanobutyronitrile to 2-amino-4-methyl-5-phenylfuran-3-carbonitrile
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Cyclization of 3-benzoyl-2-cyanobutyronitrile to 2-amino-4-methyl-5-phenylfuran-3-carbonitrile was effected under acidic conditions, rather than the basic conditions previously reported. Since treatment with trifluoroacetic acid (TFA) at room temperature is very mild, 2-amino-4-methyl-5-phenylfuran-3-carbonitriles containing various functional groups can be accessed via this route.
- Watanuki, Susumu,Sakamoto, Shuichi,Harada, Hironori,Kikuchi, Kazumi,Kuramochi, Takahiro,Kawaguchi, Ken-Ichi,Okazaki, Toshio,Tsukamoto, Shin-Ichi
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p. 127 - 130
(2007/10/03)
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- N-aminoimidazole derivatives inhibiting retroviral replication via a yet unidentified mode of action
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The synthesis of a series of N-aminoimidazoles (NAIMs) with an uncommon spectrum of antiretroviral activity is described. From a group of 60 closely related molecules, we were able to subdivide the molecules in different groups based on their anti-HIV and anti-SIV activity in vitro: (i) molecules acting on a new, immediate postintegration step, (ii) molecules acting on both postintegration and HIV-1 reverse transcriptase (RT) as NNRTI, and (iii) molecules that mainly act at the HIV-1 RT according to an NNRTI-type mode of action.
- Lagoja, Irene M.,Pannecouque, Christophe,Van Aerschot, Arthur,Witvrouw, Myriam,Debyser, Zeger,Balzarini, Jan,Herdewijn, Piet,De Clercq, Erik
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p. 1546 - 1553
(2007/10/03)
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- Chiral 3,6-dihydro-2H-1,4-oxazin-2-ones as alanine equivalents for the asymmetric synthesis of α-methyl α-amino acids (AMAAs) under mild reaction conditions
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3,6-Dihydro-2H-1,4-oxazin-2-ones 1 act as very reactive chiral cyclic alanine equivalents and can be diastereoselectively alkylated or allylated using mild reaction conditions: potassium carbonate under phase-transfer catalysis (PTC) conditions when using activated alkyl halides, organic bases such as tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2- diazaphosphorine (BEMP) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) when using unactivated alkyl halides, and neutral Pd(0)-catalysis when allylic carbonates are used. In most cases, the diastereoselectivity under all these different reaction conditions is excellent although the reactions are always carried out at room temperature. Hydrolysis of the obtained alkylated or allylated oxazinones allows the preparation of enantiomerically enriched (S)- α-methyl α-amino acids (S)-AMAAs. The PTC and organic base methodologies have also been applied to the synthesis of (R)-α-methyl α-amino acids starting from (R)-alanine. When dihalides are used as electrophiles under PTC or BEMP conditions, a spontaneous N-alkylation also takes place giving bicyclic oxazinones, which can be hydrolyzed to enantiomerically pure cyclic (S)-AMAAs.
- Chinchilla, Rafael,Galindo, Nuria,Nájera, Carmen
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p. 704 - 717
(2007/10/03)
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- Synthesis and Anti-tetrabenazine Activity of C-3 Analogues of Dimethyl-2-phenylmorpholines
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A series of analogues of 2-phenylmorpholines with alkyl substituents at the C-3 position were synthesized for anti-tetrabenazine (anti-TBZ) testing in mice.The target compounds were prepared by reaction of (2-bromoalkyl) phenyl ketones 21a-h with the appropriate aminoalcohol 20a-b to form morpholinols 22a-h.Hydride reduction of the morpholinols gave aminodiols 23a-h which were cyclized to morpholines 6, 8, 10-12, 14-16, 18 and 19 by acid catalysis.Compounds 7, 9, 13 and 17 were prepared by reductive formylation.The smaller straight chain substituents of 6, 8, 12 and 15, and the beta branching of the iso-butyl group of 16 were well tolerated; anti-tetrabenazine ED50's were comparable to compounds 2-5.The α-branched, N-methylated, and side chain aryl derivatives were less active.
- Boswell, G. Evan,Musso, David L.,Kelley, James L.,Soroko, Francis E.,Cooper, Barret R.
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- Diastereoselective synthesis and optical resolution of 3,4-substituted tetrahydroisoquinolin-4-ols
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Trans-3,4-substituted 1,2,3,4-tetrahydroisoquinolin-4-ols were prepared diastereoselectively by an insertion reaction with zerovalent nickel and by Barbier reaction with butyllithium of N-(2-iodobenzyl)phenacylamines. The isoquinolin-4-ols were resolved by means of HPLC method and the absolute configurations were determined.
- Kihara, Masaru,Ikeuchi, Motoki,Jinno, Kaori,Kashimoto, Minoru,Kobayashi, Yoshimaro,Nagao, Yoshimitsu
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p. 1017 - 1024
(2007/10/02)
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- A Facile One-Pot Synthesis of Vicinal Di- and Triketones from α-Methylene Ketones by NBS-DMSO Oxidation
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The reaction of 1,2-diarylethanones (1a-u) with N-bromosuccinimide in anhydrous dimethyl sulphoxide afforded diarylethanediones (2a-u) in excellent yields.Under similar conditions, 1-phenyl-2-butanone (3) gave 1-phenyl-1,2-butanedione (4) in fair yield in addition to a small amount of 1-phenyl-3-methylthio-1,2-butanedione (5) and 1-phenyl-1-methylthio-2-butanone (6). 4-Phenyl-2-butanone (7), 1,3-diphenyl-2-propanone (9), and 1,3-diphenyl-1,3-propanedione (10) gave the corresponding triketones monohydrate (8) and (11). 1-Indanone (12), 2-indanone (13), and 1,3-indandione (14) gave ninhydrin (15) in good yields.In the case of 3-phenyl-1-indanone (16), 3-phenyl-2-bromo-1-indanone (17), 3-phenyl-2-bromo-1-indenone (18) and 3-phenyl-1-indenone (19) were obtained. 1-Phenyl-1-propanone (20) and 1-phenyl-1-butanone (22) gave the corresponding α-(methylthio)ketones (21) and (22). 1,3,3-Triphenylpropanone (24a) and 1-phenyl-3-methyl-1-butanone (24b) yielded only the corresponding α-bromoketones (25a,b) in good yields.These α-bromoketones, however, afforded the corresponding α-diketones (26a,b) in moderate yields when α-bromoketones reacted with dimethyl sulphoxide in the presence of AgBF4.
- Tatsugi, Jiro,Izawa, Yasuji
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p. 2747 - 2763
(2007/10/02)
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