90026-47-4Relevant articles and documents
Synthesis of Enantiomerically Pure β-Hydroxy Ketones via β-Keto Weinreb Amides by a Condensation/Asymmetric-Hydrogenation/Acylation Sequence
Diehl, Julian,Brückner, Reinhard
supporting information, p. 278 - 286 (2017/01/24)
An established route to enantiomerically pure β-hydroxy ketones proceeds through the asymmetric hydrogenation of β-keto esters, an ester/amide exchange, and the use of the resulting β-hydroxy amide for the acylation of an organometallic compound. We shortened this route by showing that β-keto Weinreb amides are hydrogenated with up to 99 % ee in the presence of [Me2NH2]+{[RuCl(S)-BINAP]2(μ-Cl)3}–(0.5 mol-%) at room temp./5 bar. These Weinreb amides were prepared by seemingly obvious yet unprecedented condensations of lithiated N-methoxy-N-methylacetamide with carboxylic chlorides (51–87 % yield). The resulting β-hydroxy Weinreb amides were used for the acylation of organolithium and Grignard reagents. They thus gave enantiomerically pure β-hydroxy ketones (28 examples). A selection of these compounds gave anti-1,3-diols after another C=O bond hydrogenation, or syn-1,3-diols by a Narasaka–Prasad reduction.
Asymmetric chemoenzymatic synthesis of 1,3-diols and 2,4-disubstituted aryloxetanes by using whole cell biocatalysts
Vitale, Paola,Perna, Filippo Maria,Agrimi, Gennaro,Scilimati, Antonio,Salomone, Antonio,Cardellicchio, Cosimo,Capriati, Vito
, p. 11438 - 11445 (2016/12/16)
Regio- and stereo-selective reduction of substituted 1,3-aryldiketones, investigated in the presence of different whole cell microorganisms, was found to afford β-hydroxyketones or 1,3-diols in very good yields (up to 95%) and enantiomeric excesses (up to 96%). The enantiomerically enriched aldols, obtained with the opposite stereo-preference by baker's yeast and Lactobacillus reuteri DSM 20016 bioreduction, could then be diastereoselectively transformed into optically active syn- or anti-1,3-diols by a careful choice of the chemical reducing agent (diastereomeric ratio up to 98 : 2). The latter, in turn, were stereospecifically cyclized into the corresponding oxetanes in 43-98% yields and in up to 94% ee, thereby giving a diverse selection of stereo-defined 2,4-disubstituted aryloxetanes.
Exploring the potential of some yeast strains in the stereoselective synthesis of aldol reaction products and its reduced 1,3-dialcohol derivatives
Andreu, Cecilia,Del Olmo, Marcelli
, p. 57 - 61 (2013/06/27)
The behavior of two yeast strains has been studied under different conditions. Both microorganims catalyzed the aldol reaction between activated aldehydes and acetone when a large amount of the latter was present in the reaction medium producing, with mod
Asymmetric synthesis of new chiral 1,2- and 1,3-diols
Yildiz, Tülay,Yusufo?lu, Ay?e
, p. 183 - 190 (2013/07/27)
Seven chiral 1,2-diols and six chiral 1,3-diols were synthesized by the asymmetric reduction of the corresponding 1,2-diketones and 1,3-diketones using oxazaborolidine-BH3 catalyst. The 13 corresponding racemic 1,2- and 1,3-diols were synthesized by reducing the diketones with NaBH4 and they were used for determining the ee values through their chiral resolution on HPLC and GC. Five starting diketones, four racemic 1,2-diols, five chiral 1,2-diols, and two chiral 1,3-diols are novel compounds. The new chiral compounds were characterized by IR, 1H and 13C NMR, MS, and elemental analysis. The asymmetric reduction method, oxazaborolidine-BH 3, was applied to these diketones for the first time in this study. The relationship between the structure of the diketone and the yield, diastereoselectivity, and enantiomeric excess was discussed.
Albumin-directed stereoselective reduction of 1,3-diketones and β-hydroxyketones to anti diols
Berti, Federico,Bincoletto, Simone,Donati, Ivan,Fontanive, Giampaolo,Fregonese, Massimo,Benedetti, Fabio
experimental part, p. 1987 - 1999 (2011/04/25)
The reduction of 1,3-diketones and β-hydroxyketones with NaBH 4 in aqueous acetonitrile is highly stereoselective in the presence of stoichiometric amounts of bovine or human albumin, giving anti 1,3-diols with d.e. up to 96%. The same reaction, without albumin, gives syn and anti 1,3-diols in approximately 1:1 ratio. The presence of an aromatic carbonyl group is essential for diastereoselectivity in the NaBH4/albumin reduction of both 1,3-diketones and β-hydroxyketones. Thus, 3-hydroxy-1-(p-tolyl)-1- butanone is stereoselectively reduced in the presence of albumin, while reduction of its isomer 4-(p-tolyl)-4-hydroxy-2-butanone is not stereoselective. The albumin-controlled reduction is not stereospecific as both enantiomers of 1-aryl-3-hydroxy-1-butanones are reduced to diols with identical stereoselectivities. Circular dichroism of the bound substrates confirms that aromatic ketones are recognized by the protein's IIA binding site. Binding studies also suggest that 1,3-diketones are recognized in their enol form. From the effect of pH on binding of a diketone it is concluded that, in the complex with the substrate, ionizable residues His242 and Lys199 are in the neutral and protonated forms, respectively. A homology model of BSA was obtained and docking of model substrates confirms the preference of the protein for aromatic ketones. Modelling of the complexes with the substrates also allows us to propose a mechanism for the reduction of 1,3-diketones in which the chemoselective reduction of the first (aliphatic) carbonyl is followed by the diastereoselective reduction of the second (aromatic) carbonyl. The role of albumin is thus a combination of chemo- and stereocontrol.
Catalytic 1,3-difunctionalisation of organic backbones through a highly stereoselective, one-pot, boron conjugate-addition/reduction/oxidation process
Sole, Cristina,Tatla, Amolak,Mata, Jose A.,Whiting, Andrew,Gulyas, Henrik,Fernandez, Elena
supporting information; experimental part, p. 14248 - 14257 (2012/01/19)
A simple one-pot, three-step synthetic route to chiral 1,3-amino alcohols and 1,3-diols has been established. Considering the overall stereocontrol of the synthetic protocol, the first and key step is an enantioselective β-boration of α,β-unsaturated imin
Baker's yeast reduction of β-hydroxy ketones
Acetti, Daniela,Brenna, Elisabetta,Fuganti, Claudio,Gatti, Francesco G.,Serra, Stefano
experimental part, p. 142 - 151 (2010/03/24)
Reduction of β-hydroxy ketones to the corresponding 1,3-diols by baker's yeast was investigated, in order to develop methods for simultaneous control over the configurations of multiple stereogenic centres. The reactions were found to be enantiospecific a
Enzyme directed diastereoselectivity in chemical reductions: Studies towards the preparation of all four isomers of 1-phenyl-1,3-butanediol
Ahmad,Koul,Taneja,Singh,Kapoor,Riyaz-ul-Hassan,Verma,Qazi
, p. 1685 - 1692 (2007/10/03)
Enzymes play an important role in guiding the diastereoselectivity of the final products during the chemical reduction of the intermediates (R)- and (S)-3-hydroxy-1-phenyl-1-butanone, prepared by bioreduction of 1-phenyl-1,3-butadione. For example, the pr
Chiral epoxides as a source of chiral β-oxidofunctionalised organolithium compounds: Reaction with electrophiles
Bachki, Abderrazak,Foubelo, Francisco,Yus, Miguel
, p. 2997 - 3008 (2007/10/03)
The reductive opening of chiral epoxides 1, 4, 7 and 11 with lithium powder and a catalytic amount of DTBB (5 mol %) in THF at -78°C, followed by treatment with different electrophiles [Bu(t)CHO, PhCHO, (CH2)5CO, PhCOMe, CO2/su
Chiral β-oxidofunctionalised organolithium compounds from epoxides: EPC-synthesis of 1,3-diols
Bachki,Foubelo,Yus
, p. 1907 - 1910 (2007/10/03)
The reductive opening of (S)-propylene oxide (1) with lithium powder and a catalytic amount of DTBB (5 mol %) in THF -78°C followed by treatment with different carbonyl compounds [Bu(t)CHO, PhCHO, (CH2)5CO and PhCOMe] at the same temperature leads, after hydrolysis with water to the expected chiral 1,3-diols 3. The same methodology applied to both (R) and (S) protected epoxyalcohols 4 yields the expected enantiomerically pure compounds 6 and 7, which are monoprotected 1,2,4-triols; carbonation of these last two starting materials affords hydroxyacids 6d and 7d.
