The Journal of Organic Chemistry
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269 mg (55%). C21H24O2S (340.5 g/mol). Purity (HPLC): 99%, tR =
25.69 min. Exact MS (ESI): m/z = calcd for C21H25O2S [M+]
341.1570, found 341.1578. H NMR (CDCl3): δ (ppm) 1.34 (s, 9H,
2-(4-Methylphenyl)-7,8-dihydro-6H-[7]annuleno[b]-
thiophene-5-carboxylic Acid (10a). A solution of ester 9a (620
mg, 2.07 mmol) and 5 M NaOH (30 mL) in MeOH (30 mL) was
heated to reflux for 3 h. After cooling to rt, the mixture was
concentrated in vacuo and acidified with conc HCl to give a
precipitate. The mixture was cooled in an ice bath to complete the
precipitation, and the solid was filtered off, washed with 1 M HCl and
water, and dried overnight to give the acid 10a as a colorless solid. (Rf
= 0.50, MeOH/CH2Cl2 = 5:95), mp 216 °C (dec), yield 570 mg
(97%). C17H16O2S (284.4 g/mol). Purity (HPLC): 98%, tR = 21.55
min. Exact MS (APCI): m/z = calcd for C17H17O2S [MH+] 285.0944,
found 285.0947. 1H NMR (CDCl3): δ (ppm) 2.08 (quint, J = 5.9 Hz,
2H, 7-CH2), 2.36 (s, 3H, CH3), 2.81 (t, J = 5.8 Hz, 2H, 6-CH2), 3.11
(t, J = 5.7 Hz, 2H, 8-CH2), 7.10 (s, 1H, 3-H), 7.18 (d, J = 7.8 Hz, 2H,
3-CHphenyl, 5-CHphenyl), 7.42 (d, J = 7.9 Hz, 2H, 2-CHphenyl, 6-
CHphenyl), 7.73 (s, 1H, 4-CH). 13C NMR (CDCl3): δ (ppm) 21.5 (1C,
Ph-CH3), 24.0 (1C, C-7), 30.0 (1C, C-6), 31.2 (1C, C-8), 125.7 (2C,
C-2phenyl, C-6phenyl), 127.4 (1C, C-3), 129.9 (2C, C-3phenyl, C-5phenyl),
130.0 (1C, C-8a), 133.7 (1C, C-4), 134.9 (1C, C-5), 137.7 (1C, C-
1phenyl), 146.0 (1C, C-3a), 179.0 (1C, CO2H). Signals for the carbon
atoms C-2 and C-4phenyl are not seen. FT-IR (neat): ν (cm−1) = 2500
(CO2H), 1666 (CO).
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C(CH3)3), 2.06 (tt, J = 7.4/4.8 Hz, 2H, 7-CH2), 2.79 (t, J = 5.8 Hz,
2H, 6-CH2), 3.09 (t, J = 5.6 Hz, 2H, 8-CH2), 3.80 (s, 3H, CO2CH3),
7.09 (s, 1H, 4-CH), 7.39 (d, J = 8.4, 2H, 3-Hphenyl, 5-Hphenyl), 7.46 (d, J
= 8.4 Hz, 2H, 2-Hphenyl, 6-Hphenyl) 7.60 (s, 1H, 3-H). 13C NMR
(CDCl3): δ (ppm) 24.2 (1C, C-7), 30.5 (1C, C-6), 31.3 (1C, C-8),
31.7 (3C, C(CH3)3), 35.1 (1C, C(CH3)3), 52.5 (1C, COOCH3), 125.7
(2C, C-2phenyl, C-6phenyl), 126.3 (2C, C-3phenyl, C-5phenyl), 127.6 (1C, C-
3), 130.7 (1C, C-1phenyl), 131.5 (1C, C-8a), 133.1 (1C, C-4), 134.1
(1C, C-5), 140.5 (1C, C-2), 145.2 (1C, C-3a), 151.0 (1C, C-4phenyl),
169.5 (1C, CO). FT-IR (neat): ν (cm−1) = 2715 (C-Hallyl), 1693
(CO), 1631 (CC).
Methyl-2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-6H-[7]-
annuleno[b]thiophene-5-carboxylate (9f). A 50 mL Rettberg
Schlenk flask was equipped with a magnetic stirring bar and closed.
The flask was flame-dried under vacuo and filled with N2. Under a
permanent flow of N2, ester 2 (300 mg, 1.44 mmol), Crabtree catalyst
(58 mg, 0.07 mmol, 5 mol %), Ag2CO3 (442 mg, 1.6 mmol, 1.1 equiv),
and 1-iodo-4-(trifluoromethyl)benzene (3f, 550 mg, 2.0 mmol, 1.4
equiv) were suspended in dry 1,4-dioxane (15 mL). The vessel was
sealed and heated to 170 °C for 72 h. After the vessel cooled to rt, the
mixture was filtered through a short silica pad (EtOAc). The filtrate
was concentrated in vacuo to give the crude product as a brown oil,
which was purified by column chromatography (EtOAc/cyclohexane =
1:9, d = 2 cm, l = 11 cm, V = 30 mL) to give a yellow solid, which was
recrystallized from acetonitrile to give the ester 9f as a yellow solid. (Rf
= 0.23, EtOAc/cyclohexane = 1:9; Rf = 0.88, EtOAc/CH2Cl2 + 5%
MeOH = 1:2), mp 97−98 °C, yield 280 mg (55%). C18H15F3O2S
(352.4 g/mol). Purity (HPLC): 99%, tR = 24.55 min. Exact MS (ESI):
m/z = calcd for C21H25O2S [M+] 341.1570, found 341.1578. 1H NMR
(CDCl3): δ (ppm) 2.07 (quint, J = 5.7 Hz, 2H, 7-CH2), 2.80 (t, J = 5.9
Hz, 2H, 6-CH2), 3.11 (t, J = 5.6 Hz, 2H, 8-CH2), 7.22 (s, 1H, 3-H),
7.61 (m, 5H, 3-Hphenyl, 5-Hphenyl, 2-Hphenyl, 6-Hphenyl, 4-CH). 13C NMR
(CDCl3): δ (ppm) 24.2 (1C, C-7), 30.5 (1C, C-6), 31.3 (1C, C-8),
52.5 (1C, COOCH3), 125.9 (2C, C-2phenyl, C-6phenyl), 126.2 (q, J = 3.8
Hz, 2C, C-3phenyl, C-5phenyl), 126.3 (m, 1C, CF3), 129.4 (1C, C-3),
131.4 (1C, C-8a), 132.5 (1C, C-4), 134.5 (1C, C-5), 137.6 (1C, C-2),
138.6 (1C, C-3a), 146.8 (1C, C-4phenyl), 169.4 (1C, CO). The signal
for (C-1phenyl) is not visible. FT-IR (neat): ν (cm−1) = 2711 (C-Hallyl),
1689 (CO), 1612 (CC).
2-(3-Methylphenyl)-7,8-dihydro-6H-[7]annuleno[b]-
thiophene-5-carboxylic Acid (10b). A solution of ester 9b (200
mg, 0.67 mmol) and 5 M NaOH (30 mL) in MeOH (30 mL) was
heated to reflux for 3 h. After cooling to rt, the mixture was
concentrated in vacuo and acidified with conc HCl to give a
precipitate. The mixture was cooled in an ice bath to complete the
precipitation, and the solid was filtered off, washed with 1 M HCl and
water, and dried overnight to give the acid 10b as a colorless solid. (Rf
= 0.34, MeOH/CH2Cl2 = 5:95; Rf =0.54, EtOAc/CH2Cl2 + 5%
MeOH = 1:2), mp 201 °C, yield 177 mg (93%). C17H16O2S (284.4 g/
mol). Purity (HPLC): 98%, tR = 21.87 min. Exact MS (APCI): m/z =
calcd for C17H17O2S [MH+] 285.0944, found 285.0949. 1H NMR
(MeOD-d4): δ (ppm) 2.03 (quint, J = 5.4 Hz, 2H, 7-CH2), 2.35 (s,
3H, Ph-CH3), 2.77 (t, J = 5.9 Hz, 2H, 6-CH2), 3.06 (t, J = 5.5 Hz, 2H,
8-CH2), 7.06 (d, J = 7.7 Hz, 1H, 4-Hphenyl), 7.17 (s, 1H, 3-CH), 7.22 (t,
J = 7.7 Hz, 1H, 5-Hphenyl), 7.29−7.38 (m, 2H, 2-Hphenyl, 6-Hphenyl), 7.44
(s, 1H, 4-CH). 13C NMR (DMSO-d6): δ (ppm) 21.1 (1C, Ph-CH3),
23.5 (1C, C-7), 29.7 (1C, C-6), 30.3 (1C, C-8), 122.3 (1C, C-6phenyl),
125.7 (1C, C-2phenyl), 128.3 (1C, C-3), 128.4 (1C, C-4phenyl), 129.2
(1C, C-5phenyl), 131.4 (1C, C-2), 131.5 (1C, C-4), 133.3 (1C, C-5),
133.8 (1C, C-1phenyl), 138.5 (1C, C-3a), 139.2 (1C, C-3phenyl), 144.6
(1C, C-8a), 169.4 (1C, CO). FT-IR (neat): ν (cm−1) = 3267
(CO2H), 1666 (CO), 1604 (CC).
Methyl 2-(4-Nitrophenyl)-7,8-dihydro-6H-[7]annulene[b]-
thiophene-5-carboxylate (9g). A 50 mL Rettberg Schlenk flask
was equipped with a magnetic stirring bar and closed. The flask was
flame-dried under vacuo and filled with N2. Under a permanent flow of
N2, ester 2 (300 mg, 1.44 mmol), Crabtree catalyst (58 mg, 0.07
mmol, 5 mol %), Ag2CO3 (442 mg, 1.6 mmol, 1.1 equiv), and 1-iodo-
4-nitrobenzene (500 mg, 2.0 mmol, 1.4 equiv) were suspended in dry
1,4-dioxane (14 mL). The vessel was sealed and heated at 170 °C for
72 h. After the vessel cooled to rt, the mixture was filtered through a
short silica pad (EtOAc). The filtrate was concentrated in vacuo to
give the crude product as a brown oil, which was purified by column
chromatography (EtOAc/cyclohexane = 1:9, d = 4 cm, l = 8 cm, V =
30 mL) to give a yellow solid, which was recrystallized from
acetonitrile to give the ester 9g as a yellow solid. (Rf = 0.93, EtOAc/
CH2Cl2 + 5% MeOH = 1:2), mp 175 °C, yield 265 mg (56%).
C17H15NO4S (329.4 g/mol). Purity (HPLC): 96%, tR = 22.99 min.
Exact MS (ESI): m/z = calcd for C17H16NO4S [MH+] 330.0801,
2-(4-n-Butylphenyl)-7,8-dihydro-6H-[7]annulene[b]-
thiophene-5-carboxylic Acid (10c). A solution of ester 9c (477 mg,
1.4 mmol) and 5 M NaOH (20 mL) in MeOH (20 mL) was heated to
reflux for 3 h. After cooling to rt, the mixture was concentrated in
vacuo and acidified with conc HCl to give a precipitate. The mixture
was cooled in an ice bath to complete the precipitation, and the solid
was filtered off, washed with 1 M HCl and water, and dried overnight
to give the acid 10c as a colorless solid. (Rf = 0.41, MeOH/CH2Cl2 =
5:95), mp 190 °C, yield 420 mg (89%). C20H22O2S (326.4 g/mol).
Purity (HPLC): 98%, tR = 24.21 min. Exact MS (APCI): m/z = calcd
for C20H23O2S [MH+] 327.1413, found 327.1415. 1H NMR (CDCl3):
δ (ppm) 0.94 (t, J = 7.3 Hz, 3H, 4-CH3n‑butyl), 1.37 (sept, J = 7.3 Hz,
2H, 3-CH2n‑butyl), 1.48−1.75 (m, 2H, 2-CH2n‑butyl), 2.08 (quint, J = 5.5
Hz, 2H, 7-CH2), 2.62 (t, J = 7.7 Hz, 2H, 1-CH2n‑butyl), 2.81 (t, J = 5.9
Hz, 2H, 6-CH2), 3.12 (t, J = 5.6 Hz, 2H, 8-CH2), 7.11 (s, 1H, 4-CH),
7.18 (d, J = 8.2 Hz, 2H, 3-CHphenyl, 5-CHphenyl), 7.44 (d, J = 8.1 Hz,
2H, 2-CHphenyl, 6-CHphenyl), 7.74 (s, 1H, 3-CH). 13C NMR (CDCl3): δ
(ppm) 14.4 (1C, C-4n‑butyl), 22.8 (1C, C-3n‑butyl), 24.2 (1C, C-7), 30.1
(1C, C-6), 31.4 (1C, C-8), 34.0 (1C, C-2n‑butyl), 35.8 (C-1n‑butyl), 125.9
(2C, C-2phenyl, C-6phenyl), 127.6 (1C, C-4), 129.4 (2C, C-3phenyl, C-
5phenyl), 129.7 (1C, C-4), 131.6 (1C, C-2), 133.9 (1C, C-5), 135.1 (1C,
C-1phenyl), 140.8 (1C, C-3a), 142.9 (1C, C-3phenyl), 146.2 (1C, C-8a),
174.1 (1C, CO). FT-IR (neat): ν (cm−1) = 2619 (CO2H), 1624
(CO), 1612 (CC).
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found 330.0795. H NMR (CDCl3): δ (ppm) 2.02−2.13 (m, 2H, 7-
CH2), 2.81 (t, J = 6.4 Hz, 2H, 6-CH2), 3.12 (t, J = 5.6 Hz, 2H, 8-CH2),
3.80 (s, 3H, CO2CH3), 7.20 (s, 1H, 4-CH), 7.60 (s, 1H, 3-CH), 7.64
(d, J = 8.9 Hz, 2H, 2-CHphenyl, 6-CHphenyl), 8.22 (d, J = 8.9 Hz, 2H, 3-
CHphenyl, 5-CHphenyl). 13C NMR (CDCl3): δ (ppm) 24.1 (1C, C-7),
30.6 (1C, C-6), 31.8 (1C, C-8), 52.6 (1C, COOCH3), 124.9 (2C, C-
3phenyl, C-5phenyl), 125.9 (2C, C-2phenyl, C-6phenyl), 130.6 (1C, C-3),
131.8 (1C, C-8a), 132.2 (1C, C-4), 134.9 (1C, C-5), 137.6 (1C, C-2),
140.4 (1C, C-4phenyl), 149.9 (1C, C-3a), 148.3 (1C, C-1phenyl), 169.3
(1C, CO). FT-IR (neat): ν (cm−1) = 2927 (C-Hallyl), 1697 (CO),
1624 (CC), 1500, 1327 (NO2).
F
dx.doi.org/10.1021/jo400692p | J. Org. Chem. XXXX, XXX, XXX−XXX