Compound 19
(1S,2R)-2-isopropylcyclohexanecarbaldehyde
From: Direct, enantioselective α-alkylation of aldehydes using simple olefins
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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
To an oven-dried 8 mL vial equipped with a teflon stir bar was added 8-methylnon-7-enal (0.3 mmol, 1 equiv.). A septum cap was affixed and the vial was purged with nitrogen followed by the addition of solvent (0.6 mL, 0.5 M). The cap was briefly removed to allow for the addition of powder catalysts – Ir[Fmppy]2(dtbbpy)PF6(9 mg, 0.009 mmol, 0.03 equiv.) and the TFA salt of (2R,5R)-2-tBu-3- Me-5-(napth-1-yl-Me)imidazolidinone (38 mg, 0.09 mmol, 0.30 equiv.). After resealing the vial, (2,4,6)-triisopropylbenzenethiol (15 µL, 0.06 mmol, 0.20 equiv) and distilled water (5.4 µL, 0.3 mmol, 1 equiv.) were added through the septum cap. The heterogeneous bright yellow solution was cooled to 0 °C and sparged with dried nitrogen for 15 minutes with gentle stirring during which the reaction became homogeneous. The nitrogen line and vent needle were removed, the vial cap was double-sealed with parafilm, and the reaction was cooled to the desired temperature. The stirred solution was irradiated with blue LED light for 48h. Yield obtained by 1H NMR analysis using benzyl ether as an internal standard (product is highly volatile). Results: 64% yield, >20:1 dr, 95% ee as a colorless oil. Analytical data: [α]D21-12.97 (c = 1.00, CHCl3); 1H NMR (500 MHz, CDCl3): δ 9.52 (d, J = 4.5 Hz, 1H), 2.23-2.17 (m, 1H), 1.77 (d, J = 7.3, 9.0 Hz, 2H), 1.71-1.65 (m, 2H), 1.62-1.58 (m, 2H), 1.39 (q, J = 13.5 Hz, 1H), 1.71-1.65 (m, 2H), 1.30-1.19 (m, 2H), 1.06 (q, J = 13.0 Hz, 1H), 0.92 (d, J = 6.8 Hz, 3H), 0.81 (d, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 205.7, 53.4, 42.7, 29.7, 26.4, 25.4, 24.8, 24.0, 21.0, 16.6; HRMS (ESI+) Calcd. for C10H18O+H, 155.1430; Found, 155.1433; IR (thin film, cm-1) 2929, 2856, 2700, 1720, 1464, 1448, 1387, 1369, 1227, 1092, 1043, 989, 925, 694; TLC (90:10 hexanes:EtOAc): Rf= 0.55. HPLC analysis of the corresponding 2-napthoyl ester (OJ, 2% iPrOH/hexane, 1.0 mL/min, 220 nm) indicates 94% ee: tR= 6.4, 8.0 min.
