The Journal of Organic Chemistry
Article
Typical Procedure for Bromolactonization of Alkenoic Acids
by Using NBS. In a 25 mL capacity round-bottom flask, 1.0 mol %
(0.01 mmol) of 5,6-difluoro-2-(1-phenylethyl)benzo[d][1,2]selenazol-
3(2H)-one (9) was dissolved in 10 mL of dry dichloromethane. To
this solution, the unsaturated acid was added (1.0 mmol) followed by
1.5 mmol of K2CO3. Reaction mixture was stirred at room temperature
for 10 min. To this, 1.2 mmol of NBS was added. Reaction mixture
was stirred at room temperature for 3 h. Progress of reaction was
monitored by TLC (hexane:ethyl acetate 8:2). Then, solvent was
evaporated under reduced pressure at 40 °C. The obtained oily
reaction mixture was extracted with hexane (10.0 mL × 4), which was
evaporated in vacuo to obtain pure bromolactone.
13C NMR (100 MHz, CDCl3) δ 176.4, 90.5, 52.8, 36.0, 35.9, 33.0,
31.4; ESMS m/z Calculated for C7H9BrO2 [M] 204.0, found 204.0.
4-Bromo-6-oxabicyclo[3.2.1]octan-7-one (19). Colorless crys-
tals.26 Yield: (140 mg, 86%), 1H NMR (400 MHz, CDCl3) δ 4.77 (t, J
= 5.0 Hz,1H), 4.38 (t, J = 4.6 Hz, 1H), 2.64 (m, 2H), 2.37 (m, 2H),
2.12 (dd, J = 16.3, 5.15 Hz, 4H), 1.90 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 177.6, 79.1, 45.2, 38.3, 32.8, 28.3, 22.6; HRMS (ESI) m/z
Calculated for C7H9BrO2 [M + H] 204.9859, found 204.9836.
6-Bromohexahydro-2H-3,5-methanocyclopenta[b]furan-2-
one (20). Brown oil.27 Yield: (267 mg, 86%), H NMR (400 MHz,
1
CDCl3) δ 4.90 (d, J = 5.0 Hz,1H), 3.82 (d, J = 1.9 Hz, 2H), 3.20 (t, J =
4.7 Hz, 1H), 2.65 (s,1H), 2.54 (dd, J = 11.2, 4.2 Hz, 1H), 2.30 (d, J =
11.6 Hz, 2H), 2.16−2.06 (m, 1H), 1.80−1.70 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 179.1, 87.7, 53.5, 45.9, 45.5, 37.6, 35.8, 34.0;
ESMS m/z Calculated for C8H9BrO2 [M] 216.0, found 216.0.
Typical Procedure for Bromoesterification from Corre-
sponding Benzoic Acids and Alkenes. In a 25 mL capacity
round-bottom flask, (10.0 mol %, 0.16 mmol) of catalyst 9, benzoic
acid (1.6 mmol) and N-Bromosuccinamide (2.4 mmol) was dissolved
in 10 mL of dichloromethane. This solution was stirred at room
temperature for 10 min. Slowly, the reaction mixture turned brown-
red. To this solution, alkene (0.18 g, 1.6 mmol) dissolved in 7 mL of
dichloromethane was added dropwise. Reaction mixture was stirred at
room temperature for 8 h. Progress of reaction was monitored by TLC
(hexane:ethyl acetate, 8:2). Then, solvent was evaporated under
reduced pressure at 40 °C, and product was purified by column
chromatography.
2-Bromocyclooctyl benzoate (21). The crude compound was
purified by column chromatography on silica gel by using
(hexane:ethyl acetate = 9:1 v/v) as mobile phase. White solid. Yield:
0.42 g (84%); mp 42−44 °C; 1H NMR (400 MHz, CDCl3) δ 8.09 (m,
2H), 7.58 (m, 1H), 7.47 (m, 2H), 5.45(m, 1H), 4.51 (m, 1H), 2.40
(m, 1H), 2.16 (m, 1H), 1.94 (m, 3H), 1.77 (m, 4H), 1.62 (m, 1H),
1.48 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 165.7, 132.96, 130.4,
129.7, 128.4, 79.9, 57.4, 32.2, 31.6, 25.9, 25.4, 25.38, 24.7; HRMS
(ESI) m/z Calculated for C15H19BrO2 [M + Na] 333.0461, found
333.0463.
5-(Bromomethyl)dihydrofuran-2(3H)-one (10). Brown oil.1g
1
Yield: (166 mg, 94%), H NMR (400 MHz, CDCl3) δ 4.79−4.72
(m,1H), 3.61−3.52 (m, 2H), 2.72−2.58 (m, 2H), 2.51−2.41 (m,1H),
2.10−2.20 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 176.2, 77.8, 34.0,
28.4,26.2; ESMS m/z Calculated for C5H7BrO2 [M] 177.9, found
177.9.
5-(Bromomethyl)-3-methyldihydrofuran-2(3H)-one (11).
Brown oil.23 In diastereomeric ratio of 7:3. Yield: (155 mg, 92%),
1H NMR (400 MHz, CDCl3) δ 4.75−4.68 and 4.58−4.50 (m,1H),
3.60−3.53 and 3.51−3.43 (m, 2H), 2.84−2.67 (m, 1H), 2.64−2.55
and 2.42−2.32 (m,1H), 2.10−2.0 and 1.73−1.65 (m, 1H), 1.28 (d, J =
7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 179.1, 178.4, 75.9, 75.8,
35.7, 35.6, 33.9, 33.85, 33.4, 16.2, 15.1; HRMS (ESI) m/z Calculated
for C6H9BrO2 [M + Na] 214.9678, found 214.9687.
5-(Bromomethyl)-4-methyldihydrofuran-2(3H)-one (12).
Brown oil.24 In diastereomeric ratio of 6.8:3.2. Yield: (150 mg,
88%); 1H NMR (400 MHz, CDCl3) δ 4.70−4.62 and 4.28−4.20
(m,1H), 3.60−3.36 (m, 2H), 2.83−2.67 (m, 2H), 2.35−2.16 (m,1H),
1.20−1.08 (d, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 175.6,
175.3, 84.5, 80.9, 37.3, 36.6, 34.1, 32.6, 32.3, 28.6, 18.4, 13.0; ESMS m/
z Calculated for C6H9BrO2 [M] 191.9, found 191.9.
5-(Bromomethyl)-3,3-dimethyldihydrofuran-2(3H)-one (13).
Light brown oil.25 Yield: (74 mg, 95%), 1H NMR (400 MHz, CDCl3)
δ 4.64 (m,1H), 3.59 (dd, J = 10.7, 4.8 Hz, 1H), 3.49 (dd, J = 10.7, 6.4
Hz, 1H), 2.29 (dd, J = 13.0, 6.4 Hz,1H), 1.95 (dd, J = 13.0, 9.5 Hz,
1H), 1.30 (d, J = 8.9 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 180.9,
74.7, 41.9, 40.5, 33.6, 24.9; HRMS (ESI) m/z Calculated for
C7H11BrO2 [M + Na] 228.9835, found 228.9820.
4-Bromo-5-methyldihydrofuran-2(3H)-one (14). Colorless oil.
Yield: (65 mg, 72%), 1H NMR (400 MHz, CDCl3) δ 4.71 (quintet, J =
6.3 Hz, 1H), 4.07 (m, 1H), 3.15 (m, 1H), 2.88 (m, 1H), 1.45 (d, J =
6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 172.8, 166.7, 83.9, 73.0,
47.9, 44.2, 43.3, 39.2, 21.9, 18.4.
2-Bromocyclooctyl 2-bromo-5-methoxybenzoate (22). The
crude compound was purified by column chromatography on silica gel
by using (hexane:ethyl acetate = 9:1 v/v) as mobile phase. Colorless
1
oil. Yield: 0.22 g (62%); H NMR (400 MHz, CDCl3) δ 7.54 (d, J =
8.8 Hz, 1H), 7.40 (d, J = 3.1 Hz, 1H), 6.90 (dd, J = 8.8, 3.1 Hz, 1H),
5.45(m, 1H), 4.48 (m, 1H), 3.84 (s, 3H), 2.38 (m, 1H), 2.15 (m, 1H),
2.04 (m, 1H), 1.93(m, 2H), 1.78 (m, 4H), 1.63 (m, 1H), 1.47 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 165.1, 158.5, 134.9, 132.98,
118.8, 116.4, 111.8, 80.8, 57.4, 55.6, 32.2, 31.6, 26.0, 25.4, 25.3, 24.6;
HRMS (ESI) m/z Calculated for C16H20Br2O3 [M + Na] 440.9671,
found 440.9682.
2-Bromocyclooctyl 2-iodo-3-methylbenzoate (23). The crude
compound was purified by column chromatography on silica gel by
using (hexane:ethyl acetate = 9.5:0.5 v/v) as mobile phase. White
solid. Yield: 0.24 g (72%); mp 68−70 °C; 1H NMR (400 MHz,
CDCl3) δ 7.46 (d, J = 7.3 Hz, 1H), 7.32 (m, 1H), 5.47 (t, J = 8.8, 1H),
4.45 (t, J = 8.1 Hz, 1H), 2.53 (s, 3H), 2.38 (m, 1H), 2.12 (m, 2H),
1.94 (m, 2H), 1.80 (m, 4H), 1.51(m, 3H); 13C NMR (100 MHz,
CDCl3) δ 167.3, 143.2, 138.6, 131.6, 127.8, 127.0, 99.8, 80.6, 57.4,
32.1, 31.7, 29.5, 25.9, 25.42, 25.39, 24.7; HRMS (ESI) m/z Calculated
for C16H20BrIO2 [M + Na] 472.9584, found 472.9584.
4-Bromo-5-phenyldihydrofuran-2(3H)-one (15). Colorless
crystals.4a Yield: (277 mg, 95%), 1H NMR (400 MHz, CDCl3) δ
7.42 (m, 5H), 5.70 (d, J = 5.25 Hz, 1H), 4.40 (m, 1H), 3.26 (dd, J =
18.2, 7.5 Hz, 1H), 3.0 (dd, J = 18.2, 6.4 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 172.9, 135.9, 129.4, 129.1, 125.4, 87.9, 45.7, 38.8;
HRMS (ESI) m/z Calculated for C10H9BrO2 [M + Na] 262.9678,
found 262.9671.
6-(Bromomethyl)tetrahydro-2H-pyran-2-one (16). Colorless
oil.5a Yield: (60 mg, 89%), 1H NMR (400 MHz, CDCl3) δ 4.48
(m,1H), 3.48 (m, 2H), 2.65−2.55 (m, 1H), 2.51−2.40 (m,1H), 2.15−
2.07 (m, 1H), 2.0−1.81 (m, 2H), 1.75−1.63 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 170.3, 78.6, 33.7, 29.4, 26.3, 18.2; HRMS (ESI) m/z
Calculated for C6H9BrO2 [M + Na] 214.9678, found 214.9680.
6-(1-Bromoheptyl)tetrahydro-2H-pyran-2-one (17). Colorless
2-Bromocyclooctyl 2-chloro-4,5-difluorobenzoate (24). The
crude compound was purified by column chromatography on silica gel
by using (hexane:ethyl acetate = 9:1 v/v) as mobile phase. White solid.
1
oil. Yield: (480 mg, 86%); H NMR (400 MHz, CDCl3) δ 4.42−4.34
(m,1H), 4.03−3.96 (m, 1H), 2.65−2.56 (m, 1H), 2.50−2.39 (m,1H),
2.05−1.8 (m, 7H), 1.63−1.50 (m, 1H), 1.31−1.21 (m, 6H), 0.86 (t, J
= 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 170.7, 81.5, 56.7, 34.1,
31.6, 29.6, 28.6, 27.8, 25.2, 22.5, 18.4, 14.0; HRMS (ESI) m/z
Calculated for C12H21BrO2 [M + H] 277.0798, found 277.0804
6-Bromohexahydro-2H-cyclopenta[b]furan-2-one (18). Col-
orless oil.5a Yield: (164 mg, 90%), 1H NMR (400 MHz, CDCl3) δ 5.05
(d, J = 6.2 Hz,1H), 4.42 (d, J = 4.4 Hz, 1H), 3.20−3.09 (m, 1H), 2.85
(dd, J = 18.5, 10.2 Hz, 1H), 2.41−2.02 (m, 4H), 1.63−1.54 (m, 1H);
1
Yield: 0.32 g (56%); mp 40−42 °C; H NMR (400 MHz, CDCl3) δ
7.80 (t, J = 9.3 Hz, 1H), 7.32 (t, J = 8.3 Hz, 1H), 5.44 (t, J = 8.7 Hz,
1H), 4.46 (t, J = 8.0 Hz, 1H), 2.38 (m, 1H), 2.16 (m, 1H), 1.95 (m,
3H), 1.78 (m, 4H), 1.62(m, 1H), 1.47 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 162.6, 153.3, 153.2, 150.76, 150.63, 149.86, 149.73, 147.36,
147.24, 130.05, 129.9, 126.4, 120.7, 120.5, 120.4, 120.2, 81.1, 57.05,
32.2, 31.6, 25.9, 25.4, 25.3, 24.6; HRMS (ESI) m/z Calculated for
C15H16BrClF2O2 [M + Na] 402.9893, found 402.9882.
9549
dx.doi.org/10.1021/jo301486c | J. Org. Chem. 2012, 77, 9541−9552