PAPER
L-Proline-Catalyzed One-Pot Synthesis of b-Alkoxy Ketones
3241
4-Methoxynonan-2-one (1d)
Liquid.
7-Methoxy-9-phenylnonane-2,5-dione (3c)
Liquid.
IR (neat): 1707, 1157 cm–1.
IR (neat): 2930, 1727, 1172 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.60 (m, 1 H), 3.25 (s, 3 H), 2.60
(dd, J = 15.8, 7.8 Hz, 1 H), 2.39 (dd, J = 15.8, 4.5 Hz, 1 H), 2.11 (s,
3 H), 1.22–1.46 (m, 8 H), 0.82 (t, J = 6.5 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 207.2, 77.3, 56.7, 48.3, 33.9, 31.9,
30.9, 24.7, 22.6, 13.9.
1H NMR (300 MHz, CDCl3): d = 7.09–7.24 (m, 5 H), 3.65 (m, 1 H),
3.27 (m, 3 H), 2.46–2.74 (m, 8 H), 2.12 (s, 3 H), 1.74 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 207.5, 206.6, 141.8, 128.3, 125.8,
76.6, 56.9, 47.4, 37.3, 36.9, 35.8, 31.4, 29.9.
Anal. Calcd for C16H22O3: C, 73.25; H, 8.45. Found: C, 73.16; H,
8.57.
Anal. Calcd for C10H20O2: C, 69.72; H, 11.70. Found: C, 69.65; H,
11.76.
1-Cyclopropyl-3-methoxy-5-phenylpentan-1-one (3d)
Liquid.
4-Ethoxynonan-2-one (1e)
Liquid.
IR (neat): 1714, 1121 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.66 (m, 1 H), 3.35–3.46 (m, 2 H),
2.60 (dd, J = 15.6, 7.5 Hz, 1 H), 2.38 (dd, J = 15.6, 5.1 Hz, 1 H),
2.10 (s, 3 H), 1.21–1.42 (m, 8 H), 1.07 (t, J = 6.9 Hz, 3 H), 0.81 (t,
J = 5.6 Hz, 3 H).
IR (neat): 2928, 1715, 1095 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.09–7.25 (m, 5 H), 3.68 (m, 1 H),
3.30 (s, 3 H), 2.81 (dd, J = 15.6, 6.6 Hz, 1 H), 2.53–2.71 (m, 3 H),
1.87–1.92 (m, 1 H), 1.73–1.81 (m, 2 H), 0.96–1.01 (m, 2 H), 0.79–
0.85 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 208.9, 141.9, 128.5, 128.3, 125.8,
76.8, 57.0, 48.0, 36.2, 31.6, 21.3, 10.9.
13C NMR (75 MHz, CDCl3): d = 207.5, 75.8, 64.7, 48.9, 34.6, 32.0,
31.2, 25.0, 22.7, 15.6, 14.0.
Anal. Calcd for C15H20O2: C, 77.55; H, 8.68. Found: C, 77.59; H,
8.67.
Anal. Calcd for C11H22O2: C, 70.92; H, 11.90. Found: C, 70.74; H,
11.79.
1-Hydroxy-6-phenylhex-3-en-2-one (4b)
Liquid.
4-Methoxydecan-2-one (1g)
Liquid.
IR (neat): 1710, 1155 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.54 (m, 1 H), 3.20 (s, 3 H), 2.55
(dd, J = 15.8, 7.5 Hz, 1 H), 2.34 (dd, J = 15.8, 4.5 Hz, 1 H), 2.06 (s,
3 H), 1.16–1.39 (m, 10 H), 0.76 (t, J = 5.9 Hz, 3 H).
IR (neat): 3518, 2902, 1704 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.10–7.27 (m, 5 H), 6.92 (dt,
J = 16.2, 6.9 Hz, 1 H), 6.09 (d, J = 16.2 Hz, 1 H), 4.33 (d, J = 3.0
Hz, 2 H), 3.25 (br s, 1 H, OH), 2.75 (t, J = 7.7 Hz, 2 H), 2.53 (q,
J = 7.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 207.1, 77.3, 56.7, 48.3, 33.9, 31.8,
30.9, 29.3, 25.1, 22.6, 14.0.
13C NMR (75 MHz, CDCl3): d = 197.8, 147.9, 140.2, 128.5, 128.2,
126.4, 126.3, 66.4, 34.3 (2C).
Anal. Calcd for C11H22O2: C, 70.92; H, 11.90. Found: C, 70.62; H,
11.72.
Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C, 75.78; H,
7.48.
5-Methoxy-7-phenylheptan-3-one (3a)
Liquid.
9-Phenylnon-6-ene-2,5-dione (4c)
Liquid.
IR (neat): 2931, 1710, 1079 cm–1.
IR (neat): 2926, 1707 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.21–7.37 (m, 5 H), 3.79 (m, 1 H),
3.40 (s, 3 H), 2.67–2.81 (m, 3 H), 2.47–2.56 (m, 3 H), 1.86 (q,
J = 7.7 Hz, 2 H), 1.10 (t, J = 7.2 Hz, 3 H).
1H NMR (300 MHz, CDCl3): d = 7.14–7.28 (m, 5 H), 6.87 (dt,
J = 16.3, 6.8, 1 H), 6.11 (d, J = 16.3, 1 H), 2.67–2.81 (m, 6 H), 2.43
(m, 2 H), 2.17 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 209.5, 141.8, 128.3, 128.2, 125.7,
76.8, 56.9, 46.9, 37.1, 35.9, 31.5, 7.7.
13C NMR (75 MHz, CDCl3): d = 207.7, 198.8, 146.7, 140.9, 130.7,
128.8, 128.6, 126.5, 37.1, 34.6, 34.4, 33.8, 30.3.
Anal. Calcd for C14H20O2: C, 76.33; H, 9.15. Found: C, 76.16; H,
9.47.
Anal. Calcd for C15H18O2: C, 78.23; H, 7.88. Found: C, 77.86; H,
7.76.
1-Hydroxy-4-methoxy-6-phenylhexan-2-one (3b)
Liquid.
Acknowledgment
IR (neat) : 3515, 2921, 1713, 1094 cm–1.
The generous financial support for this research from the Welch
Foundation (Grant No. AX-1593) is gratefully appreciated.
1H NMR (300 MHz, CDCl3): d = 7.11–7.26 (m, 5 H), 4.19 (d,
J = 4.5 Hz, 2 H), 3.66 (m, 1 H), 3.28 (s, 3 H), 3.07 (br s, 1 H, OH),
2.57–2.67 (m, 3 H), 2.44 (dd, J = 15.0, 4.5 Hz, 1 H), 1.73–1.89 (m,
2 H).
References
13C NMR (75 MHz, CDCl3): d = 208.3, 141.4, 128.5, 128.3, 126.1,
(1) Kim, B. M.; Williams, S. F.; Masamune, S. In
Comprehensive Organic Synthesis, Vol. 2; Trost, B. M.;
Fleming, I.; Heathcock, C. H., Eds.; Pergamon: Oxford,
1991, 229–275.
76.8, 69.3, 57.1, 43.4, 35.6, 31.4.
Anal. Calcd for C13H18O3: C, 70.24; H, 8.16. Found: C, 70.11; H,
8.05.
Synthesis 2006, No. 19, 3238–3242 © Thieme Stuttgart · New York