Enantioselective synthesis of highly functionalised amides by copper-catalysed vinylogous Mukaiyama aldol reaction

Marcus Frings, Daniel Goedert, Carsten Bolm
2010 Chemical Communications  
General information: All experiments were performed under argon and were at least repeated twice. Diethyl ether was distilled from sodium/benzophenone ketyl radical. Flash chromatography was carried out with Merck silica gel 60 (63-100 mesh). Analytical TLC was performed with aluminium sheets silica gel 60 F 254 (Merck), and the products were visualised by a basic aqueous solution of KMnO 4 . Optical rotation measurements were conducted with a Perkin-Elmer Model 241 polarimeter (rt, λ = 589 nm)
more » ... and are given in deg . cm 3 . g −1 . dm −1 ; concentration c is listed in g . (100 mL) −1 . NMR spectra were recorded on a Varian Mercury 300 ( 1 H: 300 MHz, 13 C: 75 MHz) or Varian Inova 400 ( 1 H: 400 MHz, 13 C: 100 MHz) spectrometer. Chemical shifts (δ) are given in ppm relative to TMS (δ = 0 ppm) or solvent residual peak of CDCl 3 (δ = 7.26 ppm) as internal standard. Coupling constants J are reported in Hz and coupling patterns are described as br = broad, s = singlet, d = doublet, t = triplet, q = quartet, sept = septet, m = multiplet. IR spectra were recorded on a Spectrum 100 spectrometer with an attached UATR device Diamond KRS-5, and wave numbers ν are reported in cm −1 with indicated relative intensities: w (weak, 0-33%), m (medium, 34-66%) and s (strong, 67-100%). Mass spectra were acquired on a Finnigan SSQ 7000 spectrometer (EI, 70 eV) and HRMS were recorded on a Finnigan MAT 95 spectrometer (EI). Elemental analyses were measured on an Elementar Vario EL instrument. Melting points were determined in open-end capillary tubes on a Büchi B-540 melting point apparatus. Analytical HPLC measurements were performed with an Agilent 1100-series or 1200-series system and chiral stationary phases (250 mm . 4.6 mm) from Chiral Technologies Inc. (E)-1-(1-Oxo-2-butenyl)-3,5-dimethyl-1H-pyrazole, 1 N,O-silyl ketene aminals 3a-c, 2 methyl 2-oxo-butyrate (5b), 3 isopropyl pyruvate (5g), 4 benzyl pyruvate (5h) 5 and sulfoximines 6a-d 6 were synthesized by following their literature protocols. Other reagents were purchased from commercial suppliers and used without further purification. General procedure for the Cu-catalysed VMAR: Under argon atmosphere a dry Schlenk tube was charged with Cu(OTf) 2 (0.0300 mmol, 10.9 mg, 0.1 equiv.) and sulfoximine 6a (0.0300 mmol, 13.9 mg, 0.1 equiv.). Dry Et 2 O (2.0 mL) was added and the green solution was stirred at rt for 30 min. Subsequently, ketoester 5 (0.30 mmol) and 2,2,2-trifluoroethanol (0.36 mmol, 26 μl, 1.2 equiv.) were added. The solution was cooled to −78 °C, followed by dropwise addition of N,O-silyl ketene aminal 3 (0.33 mmol, 1.1 equiv.). The reaction mixture was stirred for 16 h and allowed to reach rt. Then, it was directly subjected to column chromatography. Supplementary Material (ESI)
doi:10.1039/c0cc00996b pmid:20574579 fatcat:sxwoxs7gbbalplbn6buicdbeaq