Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• enantioenriched products through a carbon–carbon bond formation [1][2][3][4][5]. Recently, unsaturated 1,4-dicarbonyl compounds, such as 1,4-ketoesters [6][7][8], 1,4-diketones [9], 1,4-ketoamides [9][10] and dialkylfumarates [11], have been the substrates for this reaction. The reaction products can undergo

Organocatalytic asymmetric Michael addition of unprotected 3-substituted oxindoles to 1,4-naphthoquinone

• Jin-Sheng Yu,
• Feng Zhou,
• Yun-Lin Liu and
• Jian Zhou

Beilstein J. Org. Chem. 2012, 8, 1360–1365, doi:10.3762/bjoc.8.157

• be a powerful strategy for the α-arylation of β-ketoesters and aldehydes. Inspired by their work, we anticipated that the catalytic asymmetric addition of 3-aryloxindoles to quinones would possibly install a hydroquinone moiety at the C3 position of oxindole to furnish the desired chiral 3,3

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

• Wen-Bin Yi,
• Xin Huang,
• Zijuan Zhang,
• Dian-Rong Zhu,
• Chun Cai and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138

• , Boston, MA 02125, USA 10.3762/bjoc.8.138 Abstract A fluorous cinchona alkaloid ester has been developed as a chiral promoter for the asymmetric fluorination of β-ketoesters. It has comparable reactivity and selectivity to the nonfluorous versions of cinchona alkaloids and can be easily recovered from

• organofluorine chemistry plays an important role in the life sciences [3][4]. A fluorine atom has been introduced to the α-position of some biologically interesting β-ketoesters, such as erythromycin and sesquiterpenic drimane (Figure 1) [5][6]. The achiral fluorination of β-ketoesters can be achieved by

• imido-protected phenylglycines (up to 94% ee), indanones and tetralones (up to 91% ee), ethyl α-cyanotolyl acetates (up to 87% ee), and cyclic β-ketoesters (up to 80% ee) [15]. A catalytic approach for the cinchona alkaloids and Selectfluor combinations has also been developed [16]. The Togni group

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• reaction. Keywords: α-aminoacids; carbonyl ylides; cycloaddition; α-diazo-β-ketoesters; sulfonium ylides; Introduction The synthetic potential of diazo compounds, in particular of α-diazoketones and α-diazoesters, is greatly widened by the ability of the derived carbene or metal-carbene intermediates to

• -β-ketoesters 1, stable four- to seven-membered cyclic ylides 2 were obtained (Scheme 1); in the case of R2 = allyl, however, the ylides underwent a spontaneous [2,3]-sigmatropic rearrangement. On the other hand, the conversion of methionine-derived diazoketone 3 into the cyclic sulfonium ylide 4 was

• , yielding either a cyclic sulfonium ylide or a six-ring carbonyl ylide. In fact, it has been found that Rh(II)-catalyzed dediazoniation of α-diazo-β-ketoesters with γ-phthalimido [18][19] or related [20] substituents gives rise to cyclic carbonyl ylides, which were trapped by intermolecular cycloaddition

N-Heterocyclic carbene/Brønsted acid cooperative catalysis as a powerful tool in organic synthesis

• Rob De Vreese and
• Matthias D’hooghe

Beilstein J. Org. Chem. 2012, 8, 398–402, doi:10.3762/bjoc.8.43

• -unsaturated aldehydes [18], the enantioselective synthesis of cyclopentenes from α,β-unsaturated aldehydes and α,β-unsaturated ketones [19], and the preparation of cyclopentanes through the reaction of enals and β,γ-unsaturated α-ketoesters [20]. Discussion Recently, Rovis et al. reported that the acetate

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• Lewis acids catalyze the α-fluorination of β-ketoesters by electrophilic N–F-fluorinating reagents. Asymmetric catalysis with TADDOLato–titanium(IV) dichloride (TADDOL = α,α,α',α'-tetraaryl-(1,3-dioxolane-4,5-diyl)-dimethanol) Lewis acids produces enantiomerically enriched α-fluorinated β-ketoesters in

• ][32][33] and Shibata [34][35]. Second, the research efforts of our group towards realizing metal-catalyzed fluorinations [36][37][38] and asymmetric catalytic fluorination reactions [39], successfully channeled into the discovery of a catalytic asymmetric α-fluorination of β-ketoesters (Scheme 1) by

• means of the reagent F–TEDA and chiral titanium Lewis acid catalysts of the TiCl2(TADDOLate) type [40][41][42]. The same catalytic reaction principle has also allowed the performance of asymmetric chlorinations and brominations of β-ketoesters [43][44][45]. After the initial report [40], many metal

Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B

• Silke Dubberke,
• Muhammad Abbas and
• Bernhard Westermann

Beilstein J. Org. Chem. 2011, 7, 421–425, doi:10.3762/bjoc.7.54

• 2455, 11415 Riyadh, Saudi Arabia Martin-Luther-University, Department of Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany 10.3762/bjoc.7.54 Abstract Enantiomerically highly enriched unsaturated β-ketoesters bearing a quaternary stereocenter can be utilized as building blocks for

• synthesis of this stereogenic unit and solutions have been found, e.g., by Christoffers and d’Angelo [9][10][11]. We have already disclosed our results to obtain these products highly enantiomerically enriched by pig liver esterase (PLE) catalyzed saponification of α-substituted β-ketoesters [12][13]. We

• have now extended this methodology towards the saponification of unsaturated β-ketoesters (±)-1a,b (Scheme 1) to provide a convenient access to highly functionalized cyclohexenones in optically pure form. In addition, we show that non-racemic chiral α-substituted, β-ketoesters such as (−)-1c can be

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• (Scheme 32) [74]. Dodd et al. [75] have reported an efficient solid-support synthesis of 5-N-alkylamino and 5-N-arylaminopyrazoles 123. Heating the β-ketoesters 120 with resin-bound amines 119 in resin-compatible solvents, such as NMP or toluene, in the presence of DMAP gave the corresponding resin

Highly substituted benzannulated cyclooctanol derivatives by samarium diiodide-induced cyclizations

• Jakub Saadi,
• Irene Brüdgam and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, 1229–1245, doi:10.3762/bjoc.6.141

• described the efficient synthesis of cyclooctanol and cyclooctenol derivatives by samarium diiodide-induced 8-endo-trig and 8-endo-dig cyclizations of γ-styryl- [20][31][33] and γ-phenylalkynyl-substituted [20][32] ketoesters. Recently, we have also reported our preliminary results on cyclizations of

• an add-on to our previous observations [33], we started our experiments with the cyclization of ketoesters 5a/b containing a cycloheptanone subunit. Here only the unlike-configured [45] 5a furnished the expected benzannulated tricyclic compound 6 in moderate yield (Scheme 3). The like-configured

• ring and their neighbouring protons. The cis-vicinal protons indicated strong correlations, while the trans-vicinal protons, where the dihedral angle was close to 180°, show none or almost no correlations between each other (Figure 2). In cyclizations of the (2-propenyl)phenyl-substituted ketoesters

Systematic investigations on the reduction of 4-aryl-4-oxoesters to 1-aryl-1,4-butanediols with methanolic sodium borohydride

• Subrata Kumar Chaudhuri,
• Manabendra Saha,
• Amit Saha and
• Sanjay Bhar

Beilstein J. Org. Chem. 2010, 6, 748–755, doi:10.3762/bjoc.6.94

• describe herein our systematic investigations to elucidate the different parameters involved in these reactions and to establish their synthetic usefulness. Results and Discussion When, the γ-aryl-γ-ketoesters (1a–1f) were treated with methanolic NaBH4 (4 equiv) at room temperature (room temperature

• implies 30 °C throughout) both the oxo- and the alkoxycarbonyl moieties were reduced to give the diols (2a–2f), as shown in Scheme 1. γ-Aryl-α,β-unsaturated-γ-ketoesters (1g and 1h), on similar treatment, furnished the saturated diols (2a and 2b) by the reduction of both the keto and the ester groups

• ][22][23][24][25][26][27] for the chemoselective reduction of the keto group of all types of γ-oxoesters. Mechanistic rationale for diol formation during the reduction of a γ-aryl-α,β-unsaturated-γ-ketoester with methanolic NaBH4. Facile reduction of γ-aryl-γ-ketoesters to the corresponding diols with

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• trifluoromethylation of aliphatic alcohols and these are now commercially available. In 2008, we reported a novel fluorinated Johnson-type reagent for electrophilic trifluoromethylation of carbon-centered nucleophiles. This reagent has demonstrated high efficiency in trifluoromethylation of cyclic β-ketoesters and

• ]thiophenium salts have also demonstrated high ability for trifluoromethylation of β-ketoesters and dicyanoalkylidenes to yield the trifluoromethylated products with a quaternary carbon center, even if the substrates have a rather unreactive acyclic system. In this review, we wish to briefly provide a

• conditions to give ortho-trifluoromethylated arenes in good yields (Scheme 7). Togni’s reagent (37, see later in the text) could be used for this reaction, although product yields were as low as 11%. The reaction conditions for trifluoromethylation of silyl enol ethers and β-ketoesters were reinvestigated by

Continuous flow based catch and release protocol for the synthesis of α-ketoesters

• Alessandro Palmieri,
• Steven V. Ley,
• Anastasios Polyzos,
• Mark Ladlow and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2009, 5, No. 23, doi:10.3762/bjoc.5.23

• , Melbourne, Australia, 3169 Uniqsis, Shepreth, Cambridgeshire, SG8 6GB, United Kingdom 10.3762/bjoc.5.23 Abstract Using a combination of commercially available mesofluidic flow equipment and tubes packed with immobilised reagents and scavengers, a new synthesis of α-ketoesters is reported. Keywords: catch

• and release; flow synthesis; α-ketoesters; mesoreactor; polymer supported reagents; Introduction Organic synthesis is changing rapidly owing to the discovery of processes that challenge current dogma and lead to the invention of new chemical reactions [1][2]. Likewise, new synthesis tools are

• chemical syntheses [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. In this work we report the use of the Uniqsis FlowSyn™ continuous flow reactor [55] (Figure 1) to effect a flow-based preparation of α-ketoesters. The key feature of this process is the application of a catch and