performed on a Agilent 1100 series equipped with a chiral column (detailed for each compound below), using mixtures of n-hexane/isopropyl alcohol (IPA) as mobile phase, at 25 ºC. Analytical TLC was performed on Schleicher & Schuell F1400/LS silica gel plates and the spots were visualised under UV light (•=254 nm). For flash chromatography we employed Merck silica gel 60 (0.063-0.2 mm). HRMS was carried out in the Research Technical Services of the University of Alicante.
General procedure for the Michael reaction
To a mixture of catalyst 7 (0.024 g, 0.05 mmol) and the •-nitrostyrene derivative (0.25 mmol) in n- hexane (100 •L) was added the corresponding •-alkoxyketone (0.5 mmol) at 0 or -40 ºC. The resulting mixture was stirred at the corresponding temperature until •-nitrostyrene derivative consumption (TLC monitored). The crude reaction mixture was dissolved in CH2Cl2 and purified by column chromatography (hexane/ethyl acetate 9:1) to give the pure addition products. Spectroscopic and physical data for products 12, as well as literature reference for known products, follow:
(3S,4R)-syn-3-Methoxy-5-nitro-4-phenylpentan-2-one (syn-12aa).11a Colourless oil; Rf = 0.32 (hexane/ethyl acetate 4:1); 1H NMR (300 MHz, CDCl3): • 1.77 (s, 3H, OCCH3), 3.45 (s, 3H, OCH3), 3.80-3.93 (m, 2H, CHAr and CHO), 4.66 (dd, J = 6.8 Hz, 12.9 Hz, 1H, HCHNO), 4.93 (dd, J = 8.4, 12.9 Hz, 1H, HCHNO), 7.20-7.37 (5H, ArH); 13C NMR (75 MHz, CDCl3): • 26.6 (OCCH3), 46.3 (CHAr), 59.8 (OCH3), 76.5 (CH2NO2), 86.7 (CHOCH3), 128.3 (ArCH), 128.4 (2xArCH), 128.9 (2xArCH), 134.4 (ArC), 209.9 (C=O).
(3S,4S)-anti-3-Methoxy-5-nitro-4-phenylpentan-2-one (anti-12aa).11a Colourless oil; Rf = 0.35 (hexane/ethyl acetate 4:1) 1H NMR (300 MHz, CDCl3): • 2.03 (s, 3H, OCCH3), 3.67 (s, 3H, OCH3), 3.78-3.91 (m, 2H, CHAr and CHO), 4.72 (dd, J = 6.8, 13.2 Hz, 1H, HCHNO), 4.84 (dd, J = 5.6, 13.4 Hz, 1H, HCHNO), 7.23-7.38, 5H, ArH); 13C NMR (75 MHz, CDCl3): • 26.2 (OCCH3), 45.9 (CHAr), 58.8 (OCH3), 76.7 (CH2NO2), 88.1 (CHOCH3), 128.1 (2xArCH), 128.4 (ArCH), 129.1 (2xArCH), 135.5 (ArC), 208.1 (C=O).
HPLC (Chiralpak AD; 1.0 mL/min; 96:4 hex/IPA, 210 nm); tRmajor (anti-12aa) = 35.4, tRminor(anti- 12aa) = 59.2; tRmajor (syn-12aa) = 20.3, tRminin (syn-12aa) = 30.4.
4-(4-Chlorophenyl)-3-methoxy-5-nitropentan-2-one (anti-12ab/syn-12ab). Colourless oil; Rf = 0.36 (hexane/ethyl acetate 4:1); IR (film): • 3305, 3170, 2918, 2833, 1718, 1550, 1491, 1377, 1310, 1186, 1092, 841 cm-1; 1H NMR (300 MHz, CDCl3): • 1.83 (s, 3H, OCCH3), 3.46 (s, 3H, OCH3), 3.86-3.93 (m, 2H, CHAr and CHO), 4.63 (dd, J = 12.9, 6.8 Hz, 1H, HCHNO), 4.89 (dd, J = 12.9, 8.1 Hz, 1H, HCHNO), 7.21 (d, J = 8.6 Hz, 2H, ArH), 7.29 (d, J = 8.6 Hz, 2H, ArH); 13C RMN (75 MHz, CDCl3): • 26.6 (OCCH3), 45.6 (CHAr), 59.8 (OCH3), 76.4 (CH2NO2), 86.5 (CHOCH3), 129.0 (ArCH), 129.4 (ArCH), 132.8 (ArC), 134.4 (ArC), 209.4 (C=O); HRMS (m/z): calculated for C14H16NO7 (M+): 271.0611; found 275.0581
HPLC (Chiralpak AD; 1.0 mL/min; 90:10 Hex/IPA, 210 nm); tRminor (anti-12ab) = 9.34, tRmayor (anti-12ab) = 10.1; tRmajor (syn-12ab) = 7.1, tRminor (syn-12ab) = 7.8.
