The effect of fluoromethyl groups on the diastereoselectivity in the electrophilic alkylation

Tamura, Kenji; Yamazaki, Takashi; Kitazume, Tomoya; Kubota, Toshio

doi:10.1016/j.jfluchem.2005.04.001

Cited by 11 publications

(5 citation statements)

References 30 publications

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“…α-Hydrazino esters similar to 25 are known in the literature: they are typically prepared from addition of preformed enolates to dialkyl azodicarboxylates. The enolates are typically formed at low temperatures (as low as −78 °C) with a strong base such as lithium hexamethyldisilazide (LiHMDS), tert -butyllithium, or n -butyllithium, prior to addition to dialkyl azodicarboxylates. A base screening study was carried out for the α-hydrazination of ester 23 by di- tert -butyl azodicarboxylate in order to identify conditions more amenable to scale-ups, such as mild bases, room temperature, and avoidance of preformed enolates (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of HCV Replicase Inhibitors: Base-Catalyzed Synthesis of Protected α-Hydrazino Esters and Selective Aerobic Oxidation with Catalytic Pt/Bi/C for Synthesis of Imidazole-4,5-dicarbaldehyde

et al. 2013

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A robust convergent synthesis of the prodrugs of HCV replicase inhibitors 1-5 is described. The central 5H-imidazo[4,5-d]pyridazine core was formed from acid-catalyzed cyclocondensation of an imidazole-4,5-dicarbaldehyde (20) and a α-hydrazino ester, generated in situ from the bis-BOC-protected precursors 25 and 33. The acidic conditions not only released the otherwise unstable α-hydrazino esters but also were the key to avoid facile decarboxylation to the parent drugs from the carboxylic ester prodrugs 1-5. The bis-BOC α-hydrazino esters 25 and 33 were prepared by addition of ester enolates (from 23 and 32) to di-tert-butyl azodicarboxylate via catalysis with mild inorganic bases, such as Li2CO3. A selective aerobic oxidation with catalytic 5% Pt-Bi/C in aqueous KOH was developed to provide the dicarbaldehyde 20 from the diol 27.

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Section: Resultsmentioning

confidence: 99%

Synthesis of HCV Replicase Inhibitors: Base-Catalyzed Synthesis of Protected α-Hydrazino Esters and Selective Aerobic Oxidation with Catalytic Pt/Bi/C for Synthesis of Imidazole-4,5-dicarbaldehyde

et al. 2013

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“…The enantiomeric purity was determined by HPLC analysis as 99% ee; [Chiralcel OD-H, n-hexane/i-PrOH = 70/30, flow rate 0.5 mL/min, λ = 232 nm, τ maj = 24.4 min, τ min = 27. 1 At N 2 atmosphere, to 20 mol % (0.010 mmol) of catalyst complex Zn(NTf 2 ) 2 /(R, R)-Ph-dbfox prepared as described above in 0.2 mL CH 2 Cl 2 was sequentially added 4 Å MS (15.0 mg), β-CF 3 acrylates 1a (10.5 mg, 0.050 mmol), and the solution of pyrrole (20.0 mg, 0.250 mmol) in 0.05 mL CH 2 Cl 2 . The mixture was stirred at -75 ℃ for 24 h, then passed through a plug of silica gel using 2:1 petroleum ether:ethyl acetate to afford the title compound (14.0 mg, 96%) as a white solid.…”

Section: -[444-trifluoro-3-(1h-pyrrol-2-yl)-butyryl]-oxazolidin-2-on E (3b)mentioning

confidence: 99%

Enantioselective Friedel−Crafts Reaction of β-Trifluoromethylated Acrylates with Pyrroles and Its Application to the Synthesis of Trifluorinated Heliotridane

Huang¹,

Tokunaga²,

Suzuki³

et al. 2010

Org. Lett.

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Table of Contents General Methods S1-S2 Synthesis of β-CF 3 Acrylates (1) S2 General Catalytic Procedure for the Asymmetric Friedel-Crafts Reactions S2 Characterization Data of the Asymmetric FC Reaction Products (3a-3o) S3-S10 Synthesis of Optically Active Trifluoromethylated Heliotridane S10-S12 Absolute Stereochemistry Determination S13-S14 1 H, 13 C, and 19 F NMR Spectra S15-S84 HPLC Charts S85-S92 General MethodsAll reactions were performed in oven-dried glassware under a nitrogen atmosphere, except where noted. Chemicals and solvents were purchased from commercial suppliers and used as received, excepting as follows. Dichloromethane, THF, ether, and toluene were dried by passing through an activated column. All reactions were monitored by TLC, or 19 F NMR. TLC analysis was performed by illumination with a UV lamp (254 nm), S2 staining with I 2 , or PMA [phosphomolybdic acid (5 g) in ethanol (100 ml)] and heating. All flash chromatography was packed with silica-gel (60 N spherical neutral size 63-210 µm) as the stationary phase. 1 H NMR (600 MHz) spectra were recorded on a Bruker Avance 600 instrument in CDCl 3 (7.26), or CD 2 Cl 2 (5.24), and chemical shifts were measured relative to residual solvent peak. Chemical shifts (δ) are expressed in ppm downfield from internal TMS. Data are reported as follows: Chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublet, dt = doublet of triplet, dq = doublet of quartet, m = multiplet, br = broad), coupling constant(s) and integration. 13 C NMR (150.9 MHz) spectra were recorded on a Bruker Avance 600 instrument. Chemical shifts are reported in parts per million (ppm) down field from TMS, using the middle resonance of CDCl 3 (77.23), or CD 2 Cl 2 (53.73) as an internal standard. 19 F NMR (188 MHz) was recorded on a Varian Mercury 200 instrument using CFCl 3 (0) as an internal standard. HPLC analysis were performed on a JASCO U-2080 plus using 4.6 x 250 mm CHIRALPAK OD-H or CHIRALCEL AD-H column. Optical rotations were measured on a HORIBA SEPA-300. Infrared spectra were recorded on a JASCO FT/IR-200 spectrometer. Mass spectra were recorded on a SHIMADZU GCMS-QP5050A or SHIMADZU LCMS-2010EV. High resolution mass spectra (HRMS)

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“…Acid 16 was converted to the oxazolidinone derivative 10a by reacting with ( S )-benzyloxazolidinone using a standard protocol . It should be noted that conversion of acid 16 to an alkyl ester followed by enolate generation and treatment with an N-electrophile (e.g., TrisN 3 ) is expected to produce a diastereomer opposite to the required one . A two-step approach through α-bromination followed by azidation was not desirable ( vide supra ).…”

Section: Introductionmentioning

confidence: 99%

Practical Enantioselective Synthesis of a 3-Aryl-3-trifluoromethyl-2-aminopropanol Derivative

Alimardanov

Nikitenko

Connolly

et al. 2009

Org. Process Res. Dev.

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Development of a large-scale enantioselective synthesis of a lead compound containing a 3-aryl-3-trifluoromethyl-2-aminopropanol core is described. A single isomer of 3,3-disubstituted acrylic acid derivative was prepared via Perkin condensation or Horner-Wadsworth-Emmons olefination, followed by hydrolysis. The acid was converted to a chiral acryloxazolidinone derivative. Hydrogenation of the latter on Pd/C in the presence of MgBr 2 proceeded via a chelation-controlled conformation to yield the desired isomer with high selectivity. Subsequent Evans azidation, hydrogenation, reductive cleavage of the chiral auxiliary, and sulfonylation afforded the target compound as a single isomer in high overall yield.

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The effect of fluoromethyl groups on the diastereoselectivity in the electrophilic alkylation

Cited by 11 publications

References 30 publications

Synthesis of HCV Replicase Inhibitors: Base-Catalyzed Synthesis of Protected α-Hydrazino Esters and Selective Aerobic Oxidation with Catalytic Pt/Bi/C for Synthesis of Imidazole-4,5-dicarbaldehyde

Synthesis of HCV Replicase Inhibitors: Base-Catalyzed Synthesis of Protected α-Hydrazino Esters and Selective Aerobic Oxidation with Catalytic Pt/Bi/C for Synthesis of Imidazole-4,5-dicarbaldehyde

Enantioselective Friedel−Crafts Reaction of β-Trifluoromethylated Acrylates with Pyrroles and Its Application to the Synthesis of Trifluorinated Heliotridane

Practical Enantioselective Synthesis of a 3-Aryl-3-trifluoromethyl-2-aminopropanol Derivative

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