CAPÍTULO II.- MARCO TEÓRICO
D. Principio de Protección:
II. La Cosa Juzgada
8. Competencia
General Method A. Under an atmosphere of nitrogen, to a stirred solution of aryl bromide 2 (5
equiv) drop-wise over 15 minutes at -78 °C. The solution was stirred for an additional 15 minutes at -78°C and then a solution of lactone (1 or 5) (5 mmol, 1.0 equiv) in Et2O (20 mL)
was added drop-wise. The reaction was allowed to warm to room temperature and stirred for 2 hours. Brine (75 mL) was added to quench the reaction and the organic layer was removed. The aqueous layer was extracted with EtOAc (2 × 50 mL) and CHCl3 (2 × 50 mL). All the combined
organic portions were dried over MgSO4, filtered and concentrated under reduced pressure. The
residue was purified by flash column chromatography (SiO2, hexanes/EtOAc) to afford
hydroxyarylketone 3 or 7.
General Method B. Under an atmosphere of nitrogen, to a stirred solution of aryl bromide 2 (5
mmol, 1.0 equiv) in dry Et2O (40 mL) was added a solution of BuLi in hexanes (6 mmol, 1.2
equiv) drop-wise over 15 minutes at -78 °C. The solution was stirred for an additional 15 minutes at -78°C and then added vial cannula to a solution of lactone (5) (5 mmol, 1.0 equiv) in
Et2O (40 mL) at -78 °C. The reaction was allowed to warm to room temperature and stirred for 2
hours. Brine (75 mL) was added to quench the reaction and the organic layer was removed. The aqueous layer was extracted with EtOAc (2 × 50 mL) and CHCl3 (2 × 50 mL). All the combined
organic portions were dried over MgSO4, filtered and concentrated under reduced pressure. The
residue was purified by flash column chromatography (SiO2, hexanes/EtOAc) to afford the
OH O
5-Hydroxy-1-phenylpentan-1-one (3a).2 Compound 3a was prepared by General Method A and
obtained as a slight yellow oil (565 mg, 79% yield). 1H NMR (400 MHz, CDCl
3) δ 1.61-1.68 (m,
2H), 1.79-1.87 (m, 2H), 1.99 (s, 1H), 3.02 (t, J = 7.1, 2H), 3.66 (t, J = 6.3, 2H), 7.45 (t, J = 7.9, 2H), 7.55 (t, J = 7.4, 1H), 7.95 (m, 2H). 13C NMR (101 MHz, CDCl
3) δ 20.4, 32.4, 38.3, 62.6,
128.3, 128.8, 133.3, 137.1, 200.7. Anal. Calcd. for C11H14O2: C, 74.13; H, 7.92. Found: C, 73.63;
H, 7.98.
OH O
5-Hydroxy-1-p-tolylpentan-1-one (3b).1c Compound 3b was prepared by General Method A
and obtained as a white solid (837 mg, 87% yield), mp 36-38°C. 1H NMR (400 MHz, CDCl3) δ
1.56-1.75 (m, 3H), 1.84 (m, 2H), 2.38 (s, 3H), 3.00 (t, J = 7.1, 2H), 3.67 (dd, J = 11.6, 6, 2H), 7.26 (d, J = 7.3, 2H), 7.87 (d, J = 8.2, 2H). 13C NMR (101 MHz, CDCl3) δ 20.5, 21.9, 32.5, 38.2,
62.5, 128.4, 129.5, 134.6, 144.1, 200.5. Anal. Calcd. for C12H16O2: C, 74.97; H, 8.39. Found: C,
74.75; H, 8.49.
OH O
Cl
Method A and obtained as a white solid (0.77 g, 72% yield), mp 59-61 °C. 1H NMR (400 MHz, CDCl3) δ 1.61-1.69 (m, 3H), 1.80-1.88 (m, 2H), 3.00 (t, J = 7.1, 2H), 3.68 (dd, J = 11.6, 5.8, 2H),
7.43 (d, J = 8.4, 1H), 7.90 (d, J = 8.5, 1H). 13C NMR (101 MHz, CDCl3) δ 20.4, 32.4, 38.3, 62.6,
129.1, 129.7, 135.4, 139.7, 199.3. Anal. Calcd. for C11H13ClO2: C, 62.12; H, 6.16. Found: C,
62.17; H, 6.10.
OH O
H3CO
5-Hydroxy-1-(4-methoxyphenyl)pentan-1-one (3d).3 Compound 3d was prepared by General
Method A and obtained as a colorless oil (933 mg, 90% yield). 1H NMR (400 MHz, CDCl3) δ
1.60-1.68 (m, 2H), 1.77-1.85 (m, 2H), 2.01 (s, 1H), 2.96 (t, J = 7.1, 2H), 3.65 (dd, J = 10.7, 5.9, 2H), 3.85 (s, 3H), 6.89-6.93 (m, 2H), 7.91-7.95 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 20.6,
32.5, 38.0, 55.7, 62.5, 113.9, 127.5, 130.5, 163.7, 199.3. Anal. Calcd. for C12H16O3: C, 69.21; H,
7.74. Found: C, 69.63; H, 7.74.
N
OH O
5-Hydroxy-1-(pyridin-2-yl)pentan-1-one (3g).10 Compound 3g was prepared by General
Method A and obtained as a yellow oil (730 mg, 81% yield). 1H NMR (400 MHz, CDCl3) δ
1.63-1.71 (m, 2H), 1.77-1.87 (m, 2H), 1.92 (s, 1H), 3.25 (t, J = 7.3, 2H), 3.69 (t, J = 6.1, 2H), 7.46 (ddd, J = 7.5, 4.8, 1.0, 1H), 7.83 (td, J = 7.7, 1.7, 1H), 8.03 (d, J = 7.9, 1H), 8.66 (d, J = 4.7,
1H). 13C NMR (75 MHz, CDCl3) δ 19.5, 20.3, 25.5, 32.4, 35.8, 37.4, 62.5, 62.6, 95.1, 120.2,
122.1, 123.6, 127.3, 137.2, 137.6, 147.7, 149.1, 153.5, 161.1, 202.1. Anal. Calcd. for C10H13NO2:
C, 67.02; H, 7.31; N, 7.82. Found: C, 66.96; H, 7.46; N, 7.73.
N
OH O
5-Hydroxy-1-(pyridin-3-yl)pentan-1-one (3h).1d Compound 3h was prepared by General
Method A and obtained as a yellow oil (350 mg, 63% yield). 1H NMR (400 MHz, CDCl3) δ
1.64-1.72 (m, 2H), 1.83-1.99 (m, 3H), 3.06 (t, J = 7.1, 2H), 3.70 (t, J = 6.1, 2H), 7.43 (dd, J = 8.0, 4.8, 1H), 8.25 (m, 1H), 8.77 (dd, J = 4.8, 0.8, 1H), 9.17 (d, J = 2.1, 1H). 13C NMR (101 MHz, CDCl3) δ 20.3, 32.2, 38.7, 62.3, 124.0, 132.4, 135.8, 149.6, 153.4, 199.4. Anal. Calcd. for
C10H13NO2: C, 67.02; H, 7.31; N, 7.82. Found: C, 65.74; H, 7.39; N, 7.67.
N
OH O
H3CO
5-Hydroxy-1-(6-methoxypyridin-3-yl)-pentan-1-one (3i).5 Compound 3i was prepared by
General Method A and obtained as a pale yellow solid (1.0 g, 98% yield), mp 42-44 °C. 1H NMR (400 MHz, CDCl3) δ 8.80 (d, J = 2.4 Hz, 1H),8.14 (dd, J = 8.7, 2.4 Hz, 1H), 6.79 (d, J = 8.7 Hz
1H), 4.01 (s, 3H), 3.68 (t, J = 6.3 Hz, 2H), 2.97 (t, J = 7.1 Hz, 2H), 1.92 (brs, 1H), 1.81-1.87 (m, 2H), 1.64-1.70 (m, 2H). 13C NMR (100 MHz, CDCl3) δ, 198.3, 166.9, 149.2, 138.4, 126.8, 111.4,
62.97; H, 7.19; N, 6.64.
OH O
S
5-Hydroxy-1-(thiophen-2-yl)pentan-1-one (3j). Compound 3j was prepared by General
Method A and obtained as a yellow oil (726 mg, 79% yield). 1H NMR (400 MHz, CDCl 3) δ
1.62-1.71 (m, 3H), 1.82-1.90 (m, 2H), 2.97 (t, J = 7.2, 2H), 3.67 (dd, J = 10.4, 6, 2H), 7.13 (dd, J
= 4.9, 3.8, 1H), 7.63 (dd, J = 4.9, 1.1, 1H), 7.73 (dd, J = 3.8, 1.1, 1H). 13C NMR (101 MHz, CDCl3) δ 20.9, 32.3, 39.1, 62.4, 128.4, 132.2, 133.9, 144.4, 193.8. Anal. Calcd. for C9H12O2S: C,
58.67; H, 6.56. Found: C, 58.50; H, 6.70.
OH OH
1,1-Diphenylbutane-1,4-diol (6a).1a Compound 6a was prepared by General Method A and
obtained as a white solid (393 mg, 65% yield), mp 104-106°C. 1H NMR (400 MHz, CDCl3) δ
1.54-1.61 (m, 2H), 1.94 (s, 1H), 2.41 (t, J = 7.2, 2H), 3.24 (s, 1H), 3.63 (t, J = 5.6, 2H), 7.18-7.23 (m, 2H), 7.27-7.32 (m, 4H), 7.39-7.43 (m, 4H). 13C NMR (75 MHz, CDCl3) δ 27.4, 39.2, 63.3,
78.1, 126.3, 127.0, 128.4, 147.3. Anal. Calcd. for C16H18O2: C, 79.31; H, 7.49. Found: C, 79.06;
OH OH
1,1-Ditolylbutane-1,4-diol (6b). Compound 6b was prepared by General Method A and obtained
as a white solid (486 mg, 72% yield), mp 106-108°C. 1H NMR (400 MHz, CDCl3) δ 1.53-1.62
(m, 2H), 1.83 (s, 1H), 2.31 (s, 6H), 2.38 (t, J = 7.2, 2H), 2.94 (s, 1H), 3.64 (s, 2H), 7.10 (d, J = 8.0, 4H), 7.29 (d, J = 8.2, 4H). 13C NMR (75 MHz, CDCl3) δ 21.2, 27.5, 39.2, 63.4, 78.0, 126.2,
129.1, 136.5, 144.5. Anal. Calcd. for C18H22O2: C, 79.96; H, 8.20. Found: C, 79.66; H, 8.19.
OH OH
Cl
Cl
1,1-Di(4-chlorophenyl)butane-1,4-diol (6c).9b Compound 6c was prepared by General Method
A and obtained as a white solid (529 mg, 68% yield), mp 125-127°C. 1H NMR (400 MHz,
CDCl3) δ 1.50-1.60 (m, 2H), 2.11 (s, 1H), 2.37 (t, J = 7.1, 2H), 3.64 (t, J = 5.6, 2H), 3.83 (s, 1H),
7.24-7.28 (m, 4H), 7.30-7.34 (m, 4H). 13C NMR (75 MHz, CDCl
3) δ 27.0, 39.3, 63.2, 76.5, 127.7,
OH OH
OCH3
H3CO
1,1-Di(4-methoxyphenyl)butane-1,4-diol (6d). Compound 6d was prepared by General Method
A and obtained as a colorless oil (584 mg, 77% yield). 1H NMR (400 MHz, CDCl3) δ 1.54-1.61
(m, 2H), 1.73 (s, 1H), 2.36 (t, J = 7.6, 2H), 2.83 (s, 1H), 3.66 (m, 2H), 3.78 (d, J = 6.0, 6H), 6.80-6.85 (m, 4H), 7.29-7.33 (m, 4H). 13C NMR (75 MHz, CDCl3) δ 27.5, 39.4, 55.5, 63.4, 100.2,
113.6, 127.5 139.8, 158.5. Anal. Calcd. for C18H22O4: C, 71.50; H, 7.33. Found: C, 70.69; H,
7.26.
OH OH
S S
1,1-Di(thiophen-2-yl)butane-1,4-diol (6j). Compound 6j was prepared by General Method A
and obtained as a white solid (445 mg, 70% yield, mp 94-96°C. 1H NMR (400 MHz, CDCl3) δ
1.67-1.74 (m, 2H), 1.92 (t, J = 4.9, 1H), 2.48 (t, J = 7.0, 2H), 3.70 (dd, J = 10.8, 5.7, 2H), 4.33 (s, 1H), 6.93-6.97 (m, 4H), 7.22 (dd, J = 4.9, 1.4, 2H). 13C NMR (75 MHz, CDCl3) δ 27.5, 42.9,
63.2, 76.1, 123.9, 124.8, 126.9, 152.4. Anal. Calcd. for C12H14O2S2: C, 56.66; H, 5.55. Found: C,
OH O
4-Hydroxy-1-phenylbutan-1-one (7a).6 Compound 7a was prepared by General Method B and
obtained as a colorless oil (582 mg, 71% yield). 1H NMR (400 MHz, CDCl
3) δ 1.84 (t, J = 5.3,
1H), 1.99-2.06 (m, 2H), 3.14 (t, J = 6.9, 2H), 3.75 (dd, J = 5.9, 11.3, 2H), 7.43-7.48 (m, 2H), 7.54-7.59 (m, 1H), 7.96-7.99 (m, 2H). 13C NMR (75 MHz, CDCl
3) δ 27.1, 35.5, 62.6, 128.3,
128.8, 133.4, 137.1, 200.8. Anal. Calcd. for C10H12O2: C, 73.15; H, 7.37. Found: C, 72.88; H,
7.42.
OH O
4-Hydroxy-1-p-tolylbutan-1-one (7b).4b Compound 7b was prepared by General Method B and
obtained as a white solid (593 mg, 67% yield), mp 42-44°C. 1H NMR (400 MHz, CDCl3) δ 1.86
(s, 1H), 1.98-2.05 (m, 2H), 2.41 (s, 3H), 3.11 (t, J = 6.9, 2H), 3.75 (s, 2H), 7.27 (d, J = 8.0, 2H), 7.88 (d, J = 8.2, 2H). 13C NMR (75 MHz, CDCl3) δ 21.9, 27.2, 35.5, 62.6, 128.4, 129.5, 134.6,
144.2, 200.4. Anal. Calcd. for C11H14O2: C, 74.13; H, 7.92. Found: C, 73.98; H, 7.98.
OH O
Cl
1-(4-Chlorophenyl)-4-hydroxybutan-1-one (7c).11 Compound 7c was prepared by General
1.77 (s, 1H), 1.96-2.04 (m, 2H), 3.10 (t, J = 6.9, 2H), 3.74 (t, J = 6.0, 2H), 7.44 (d, J = 8.5, 2H), 7.92 (d, J = 8.5, 2H). 13C NMR (75 MHz, CDCl3) δ 27.0, 35.4, 62.4, 129.1, 129.7, 135.4, 139.8,
199.5. Anal. Calcd. for C10H11ClO2: C, 60.46; H, 5.58. Found: C, 60.66; H, 5.81.
OH O
H3CO
4-Hydroxy-1-(4-methoxyphenyl)butan-1-one (7d).12 Compound 7d was prepared by General
Method B and obtained as a white solid (657 mg, 68% yield), mp 46-48 °C. 1H NMR (400 MHz, CDCl3) δ1.93 (t, J = 5.2, 1H), 1.97-2.04 (m, 2H), 3.08 (t, J = 6.9, 2H), 3.74 (q, J = 5.7, 2H), 3.87
(s, 3H), 6.93 (d, J = 9.0, 2H), 7.96 (d, J = 9.0, 2H). 13C NMR (75 MHz, CDCl3) δ 27.3, 35.2,
55.7, 62.6, 114.0, 127.5, 130.6, 163.7, 199.4. Anal. Calcd. for C11H14O3: C, 68.02; H, 7.27.
Found: C, 67.97; H, 7.37.
N
OH O
4-Hydroxy-1-(pyridin-2-yl)butan-1-one (7g).7 Compound 7g was prepared by General Method
A and obtained as a yellow oil (577 mg, 70% yield). 1H NMR (400 MHz, CDCl3) δ 1.98-2.05 (m,
2H), 2.57 (t, J = 5.7, 1H), 3.31 (t, J = 7.0, 2H), 3.70 (q, J = 6.0, 2H), 7.48 (ddd, J = 7.6, 4.8, 1.2, 1H), 7.84 (td, J = 7.7, 1.7, 1H), 8.03 (d, J = 7.9, 1H), 8.66 (d, J = 4.7, 1H). 13C NMR (101 MHz, CDCl3) δ 27.8, 34.5, 62.2, 122.1, 127.5, 137.3, 149.1, 153.6, 202.7. Anal. Calcd. for C9H11NO2:
N
OH O
4-Hydroxy-1-(pyridin-3-yl)butan-1-one (7h).1d Compound 7h was prepared by General
Method A and obtained as a light yellow solid (545 mg, 66% yield), mp 36-38 °C. 1H NMR (400 MHz, CDCl3) δ 1.98-2.05 (m, 2H), 2.40 (t, J = 5.1, 1H), 3.13 (t, J = 7.0, 2H), 3.74 (dd, J = 11.3,
5.8, 2H), 7.40 (dd, J = 8.0, 4.8, 1H), 8.23 (dt, J = 8.0, 2.0, 1H), 8.74 (dd, J = 4.8, 1.7, 1H), 9.16 (d, J = 2.2, 1H). 13C NMR (101 MHz, CDCl3) δ 26.8, 35.6, 61.7, 124.0, 132.4, 135.8, 149.6,
153.4, 199.4. Anal. Calcd. for C9H11NO2: C, 65.44; H, 6.71; N, 8.48. Found: C, 65.85; H, 6.82; N,
8.45.
N
OH O
H3CO
4-Hydroxy-1-(6-methoxypyridin-3-yl)butan-1-one (7i). Compound 7i was prepared by
General Method A and obtained as a pale yellow solid (0.87 g, 89% yield), mp 35-37 °C. 1H NMR (400 MHz, CDCl3) δ 8.82 (d, J = 2.4 Hz, 1H), 8.15 (dd, J = 8.7, 2.5 Hz, 1H) 6.79 (d, J =
8.7 Hz, 1H), 4.01 (s, 3H), 3.75 (d, J = 4.4 Hz, 2H), 3.08 (t, J = 6.9 Hz, 2H), 2.14 (s, 1H), 1.98-2.05 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 198.5, 167.0, 149.3, 138.4, 126.8, 111.4, 62.3,
54.3, 35.3, 27.0. Anal. Calcd. for C10H13NO3: C, 61.53; H, 6.71; N, 7.18. Found: C, 61.70; H,
OH O
S
4-Hydroxy-1-(thiophen-2-yl)butan-1-one (7j).13 Compound 7a was prepared by General
Method B and obtained as a colorless oil (641 mg, 75% yield). 1H NMR (400 MHz, CDCl 3) δ
1.87 (t, J = 5.3, 1H), 1.99-2.06 (m, 2H), 3.08 (t, J = 7.0, 2H), 3.75 (q, J = 5.8, 2H), 7.12-7.15 (m, 1H), 7.64 (dd, J = 4.9, 1.0, 1H), 7.75 (dd, J = 3.8, 1.0, 1H). 13C NMR (75 MHz, CDCl
3) δ 27.4,
36.2, 62.4, 128.4, 132.3, 133.9, 144.4, 193.7. Anal. Calcd. for C8H10O2S: C, 56.44; H, 5.92.
Found: C, 56.05; H, 6.10.
2.7. References
1. (a) Descotes, G.; Soula, J.-C. Bull. Soc. Chim. Fr.1964, 5, 2636-2639. (b) Crich, D.; Huang,
X.; Newcomb, M. Org. Lett. 1999, 1, 225-227. (c) Bailey, W. F.; Khanolkar, A. D.
Tetrahedron 1991, 47, 7727-7738. (d) Ohkawa, S.; Terao, S.; Terashita, Z.; Shibouta, Y.;
Nishikawa, K. J. Med. Chem. 1991, 34, 267-276.
2. Rosenblum, S. B.; Bihovsky, R. J. Am. Chem. Soc.1990, 112, 2746-2748.
3. (a) Atkinson, R. S. Chem. Commun. 1970, 177. (b) Atkinson, R. S. J. Chem. Soc. 1971,
784-788.
4. (a) Fuji, K.; Node, M.; Usami, Y.; Kiryu, Y. J. Chem. Soc. Chem Commun. 1987, 449-450. (b)
Fuji, K.; Usami, Y.; Kiryu, Y.; Node, M. Synthesis1992, 852-858.
5. Miao, L.; DiMaggio, S. C.; Shu, H.; Trudell, M. L. Org. Lett.2009, 11, 1579-1582.
6. Yang, S.-B.; Gan, F.-F.; Chen, G.-J.; Xu, P.-F. Synlett2008, 16, 2532-2534.
8. Whiting, J. E.; Edward, J. T. Can. J. Chem. 1971, 49, 3799-3806.
9. (a) Vozza, J. F. J. Org. Chem.1959, 24, 720-722. (b) Umio, S.; Ueda, I.; Nojima, H. J. Med.
Chem. 1972, 15, 855-856.
10. Shimizu, J.; Tsurki, T.; Yamagishi, Y.; Inchino, T. Japanese Patent JP06157459; Chem. Abstr.
1994, 121:179498.
11. Huang, N.; Xu, L. Youji Huaxue1989, 9, 436-437. Chem. Abstr.1989, 113:5301.
12. Ramadas, S. R.; Sukumaran, K. B. Ind. J. Chem. 1970, 8, 470-471.