The Journal of Organic Chemistry
Note
37.0, 32.2, 20.0; HRMS (EI) m/z [M]+ calcd for C11H13IO+
288.0011; found 288.0017.
5-Bromo-1-(4-methoxyphenyl)-1-methyl-2,3-dihydro-1H-indene
(7). Following the general procedure 2 for organocatalytic hydro-
arylation of 6-bromo-3-methyl-1H-indene. Isolated as a clear oil (30.5
General Procedure 3: Organocatalytic Hydrothiolation.
Alkene (0.1 mmol, 1 equiv) was weighed into a regular 2 mL glass
vial. In a separate regular 2 mL glass vial, p-TSA·H2O (1.9 mg, 0.01
mmol, 10 mol %) was weighed and solubilized in HFIP (0.2 mL),
CDCl3 (0.2 mL), and thiol (0.6 mmol, 6 equiv) successively. This was
then transferred to the vial containing alkene in one portion. The
reaction was left to stand for 5 h (36 h for ketoprofen) before being
quenched by addition of NaHCO3 (0.5 mL), extracted with CHCl3
(3×), and dried over Na2SO4. The titled compounds were isolated by
flash column chromatography eluting 10−40% CHCl3/hexane.
General Procedure 4: Oxidation of Thioethers. The thioether
was dissolved in CH2Cl2 (concentration of 0.05 M), and m-CPBA was
added (4 equiv). This was allowed to stir at rt for 2 h. The reaction
was quenched by addition of saturated Na2S2O3 and saturated
NaHCO3. The organic was extracted with CH2Cl2, dried over MgSO4,
and concentrated in vacuo. If necessary, flash column chromatography
eluting 50% Et2O/hexane afforded the desired compounds.
1
mg, 0.0961 mmol, 96%): H NMR (400 MHz, chloroform-d) δ 7.41
(s, 1H), 7.32 (d, J = 8.1 Hz, 1H), 7.10 (d, J = 8.8 Hz, 2H), 6.92 (d, J =
8.1 Hz, 1H), 6.81 (d, J = 8.8 Hz, 2H), 3.79 (s, 2H), 2.89 (m, 2H),
2.37 (ddd, J = 12.5, 7.8, 6.5 Hz, 1H), 2.19 (ddd, J = 12.5, 7.8, 7.5 Hz,
1H), 1.63 (s, 3H); 13C{1H} NMR (101 MHz, chloroform-d) δ 157.8,
150.5, 146.1, 140.6, 129.7, 127.8, 127.7, 125.8, 120.4, 113.5, 55.4,
51.3, 44.3, 30.4, 27.6; HRMS (EI) m/z [M+]+ calcd for C17H17OBr+
316.0457; found 316.0454.
4-Iodo-7-methoxy-1-(4-methoxyphenyl)-1-methyl-2,3-dihydro-
1H-indene (8). Following the general procedure 2 for organocatalytic
hydroarylation of alkene 23. Isolated as a clear oil (38.2 mg, 0.0969
1
mmol, 97%): H NMR (400 MHz, chloroform-d) δ 7.56 (d, J = 8.5
Hz, 1H), 7.06 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 6.51 (d, J
= 8.5 Hz, 1H), 3.78 (s, 3H), 3.62 (s, 3H), 2.92−2.80 (m, 2H), 2.2−
2.23 (m, 1H), 2.21−2.12 (m, 1H), 1.74 (s, 3H); 13C{1H} NMR (101
MHz, chloroform-d) δ 157.6, 157.2, 149.6, 140.9, 138.6, 137.4, 127.0,
113.4, 112.2, 83.3, 55.5, 55.3, 53.8, 43.5, 36.6, 26.7; HRMS (EI) m/z
1-Methoxy-4-(1-phenyl-1-(para-tolyl)ethyl)benzene (3). Follow-
+
[M]+ calcd for C18H19IO2 394.0424; found 394.0416.
ing the general procedure 2 for organocatalytic hydroarylation of
1
1-(4-Methoxyphenyl)-1-phenyl-2,3-dihydro-1H-indene (9). Fol-
lowing the general procedure 2 for organocatalytic hydroarylation of
3-phenyl-1H-indene. Isolated as a pale-yellow oil (26.0 mg, 0.0865
alkene 1. Isolated as a clear oil (22.3 mg, 0.0737 mmol, 74%): H
NMR (400 MHz, chloroform-d) δ 7.28−7.24 (m, 2H), 7.22−7.17
(m, 1H), 7.11−6.97 (m, 8H), 6.82−6.78 (m, 2H), 3.79 (s, 3H), 2.33
(s, 3H), 2.15 (s, 3H); 13C{1H} NMR (101 MHz, chloroform-d) δ
157.7, 149.7, 146.5, 141.5, 135.5, 129.8, 128.8, 128.7, 128.7, 127.9,
126.0, 113.2, 55.3, 51.7, 30.7, 21.1.
1-(4-Methoxyphenyl)-1-methyl-1,2,3,4-tetrahydronaphthalene
(4). Following the general procedure 2 for organocatalytic hydro-
arylation of 4-methyl-1,2-dihydronaphthalene. Isolated as a clear oil
(25.0 mg, 0.0991 mmol, 99%): 1H NMR (400 MHz, chloroform-d) δ
7.12−6.99 (m, 6H), 6.78 (d, J = 8.9 Hz), 3.77 (s, 3H), 2.83 (t, J = 6.5
Hz, 2H), 2.02 (ddd, J = 13.2, 8.2, 3.2 Hz, 1H), 1.86 (ddd, J = 13.2,
9.1, 3.0 Hz, 1H), 1.81−1.72 (m, 1H), 1.70 (s, 3H), 1.69−1.61 (m,
1H); 13C{1H} NMR (101 MHz, chloroform-d) δ 157.4, 144.7, 143.9,
137.1, 129.2, 129.1, 128.5, 125.9, 125.8, 113.2, 55.3, 42.4, 41.6, 30.4,
30.3, 19.7; HRMS (EI) m/z [M + H]+ calcd for C18H21O+ 253.1587;
found 253.1588.
1
mmol, 87%): H NMR (400 MHz, chloroform-d) δ 7.28−7.16 (m,
8H), 7.10−7.04 (m, 3H), 6.81 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H),
2.90−2.87 (m, 2H), 2.82−2.79 (m, 2H); 13C{1H} NMR (101 MHz,
chloroform-d) δ 157.73, 149.63, 147.51, 143.75, 139.26, 129.51,
128.47, 127.88, 126.78, 126.25, 126.04, 125.96, 124.63, 113.20, 61.20,
55.22, 43.66, 30.61; HRMS (CI) m/z [M + H]+ calcd for C22H21O+
301.1587; found 301.1578.
2-(1-Methyl-2,3-dihydro-1H-inden-1-yl)benzo[b]thiophene (13).
Following the general procedure 2 for organocatalytic hydroarylation
of 3-methyl-1H-indene. Isolated as a colorless oil (26.3 mg, 0.0994
mmol, 99%): 1H NMR (400 MHz, chloroform-d) δ 7.75 (dd, J = 7.4,
1.2 Hz, 1H), 7.64 (dd, J = 7.4, 1.2 Hz, 1H), 7.33−7.26 (m, 4H),
7.26−7.23 (m, 2H), 6.89 (d, J = 0.6 Hz, 1H), 3.15−2.91 (m, 2H),
2.59 (ddd, J = 12.8, 7.8, 5.1 Hz, 1H), 2.32 (dt, J = 12.8, 7.8 Hz, 1H),
1.82 (s, 3H); 13C{1H} NMR (101 MHz, chloroform-d) δ 155.6,
149.9, 143.2, 140.0, 139.5, 127.4, 126.8, 124.9, 124.2, 123.9, 123.7,
123.1, 122.2, 119.8, 51.0, 44.2, 30.5, 28.6; HRMS (EI) m/z [M]+
calcd for C18H16S+ 264.0967; found 264.0961.
1-(4-Methoxyphenyl)-1-methyl-2,3-dihydro-1H-indene (5). Fol-
lowing the general procedure 2 for organocatalytic hydroarylation of
3-methyl-1H-indene. Isolated as a clear oil (23.6 mg, 0.0990 mmol,
1
99%): H NMR (400 MHz, chloroform-d) δ 7.29 (ddd, J = 5.5, 2.8,
2-Methyl-5-(1-methyl-2,3-dihydro-1H-inden-1-yl)furan (14). Fol-
lowing the general procedure 2 for organocatalytic hydroarylation of
3-methyl-1H-indene. Isolated as a colorless oil (18.0 mg, 0.0849
0.9 Hz, 1H), 7.24−7.18 (m, 2H), 7.12 (d, J = 8.9 Hz, 2H), 7.09−7.06
(m, 1H), 6.82 (d, J = 8.9 Hz, 1H), 3.79 (s, 3H), 2.97−2.86 (m, 2H),
2.38 (ddd, J = 12.5, 7.6, 6.6 Hz, 1H), 2.20 (ddd, J = 12.5, 7.6, 6.6 Hz,
1H), 1.67 (s, 3H); 13C{1H} NMR (101 MHz, chloroform-d) δ 157.7,
151.4, 143.7, 141.3, 127.8, 126.7, 126.6, 124.6, 124.2, 113.4, 55.3,
51.6, 44.3, 30.5, 27.7; HRMS (CI) m/z [M + H]+ calcd for C17H19O+
239.1430; found 239.1429. On 5 mmol scale following a modified
general procedure 2 for organocatalytic hydroarylation. To 3-methyl-
1H-indene (651 mg, 5.0 mmol, 1 equiv) was added p-TSA·H2O (47.5
mg, 0.25 mmol, 5 mol %) dissolved in a solution of anisole (3.26 mL,
30 mmol, 6 equiv), 10 mL of CHCl3, and 10 mL of HFIP. This was
allowed to stir, and after 5 h was quenched by addition of NaHCO3
(25 mL), extracted with CHCl3 (3×), and dried over Na2SO4. The
titled compound was isolated by flash column chromatography eluting
10−40% CHCl3/hexane, isolated as a clear oil (989 mg, 4.15 mmol,
83%) in agreement with the small-scale characterization.
1
mmol, 85%): H NMR (400 MHz, chloroform-d) δ 7.26−7.13 (m,
4H), 5.84−5.82 (m, 1H), 5.80 (d, J = 3.0 Hz, 1H), 3.04−2.91 (m,
2H), 2.61−2.54 (m, 1H), 2.24 (d, J = 0.9 Hz, 3H), 2.14−2.01 (m,
1H), 1.59 (s, 3H); 13C{1H} NMR (101 MHz, chloroform-d) δ 159.4,
151.0, 149.1, 143.2, 126.9, 126.5, 124.7, 123.6, 105.7, 104.9, 48.7,
39.8, 30.4, 26.0, 13.8. HRMS (CI) m/z [M + H]+ calcd for C15H17O+
213.1274; found 213.1275.
5-((1RS,2RS)-2-Methyl-2,3-dihydro-1H-inden-1-yl)benzo[d][1,3]-
dioxole (15). Following the general procedure 2 for organocatalytic
hydroarylation of commercially available 2-methylindene. Isolated as a
1
colorless oil (14.6 mg, 0.0578 mmol, 58%). Crude H NMR analysis
suggested 5:3 dr, but a single diastereomer was isolated clean.
1
Stereochemistry assigned by analogy with compound 6: H NMR
(400 MHz, chloroform-d) δ 7.23 (d, J = 7.4 Hz, 1H), 7.19−7.07 (m,
2H), 6.88 (d, J = 7.4 Hz, 1H), 6.78 (d, J = 7.9 Hz, 1H), 6.72−6.62
(m, 2H), 5.96−5.93 (m, 2H), 3.72 (d, J = 9.5 Hz, 1H), 3.12 (dd, J =
15.4, 7.6 Hz, 1H), 2.71−2.54 (m, 1H), 2.46−2.31 (m, 1H), 1.17 (d, J
= 6.6 Hz, 3H); 13C{1H} NMR (101 MHz, chloroform-d) δ 147.7,
147.1, 146.1, 143.6, 137.9, 126.6, 126.3, 124.7, 124.1, 121.9, 108.7,
108.0, 100.9, 59.4, 46.3, 40.2, 18.2; HRMS (EI) m/z [M]+ calcd for
(1RS,2RS)-1-(4-Methoxyphenyl)-2-methyl-2,3-dihydro-1H-indene
(6). Following the general procedure 2 for organocatalytic hydro-
arylation of commercially available 2-methylindene. Isolated as a clear
oil (19.7 mg, 0.0827 mmol, 83%); stereochemistry assigned by NOE
analysis. For major diastereomer: 1H NMR (400 MHz, chloroform-d)
δ 7.24 (app. s, 1H), 7.21−7.09 (m, 4H), 6.94−6.79 (m, 3H), 3.82 (s,
3H), 3.75 (d, J = 10.0 Hz, 1H), 3.13 (dd, J = 15.3, 7.5 Hz, 1H), 2.64
(dd, J = 15.3, 10.0 Hz, 1H), 2.49−2.35 (m, 1H), 1.18 (d, J = 6.6 Hz,
3H); 13C{1H} NMR (101 MHz, chloroform-d) δ 158.4, 147.5, 143.8,
136.1, 129.7, 126.6, 126.4, 124.8, 124.2, 113.9, 59.0, 55.4, 46.5, 40.4,
18.3. HRMS (CI) m/z [M + H]+ calcd for C17H19O+ 239.1430; found
239.1430.
+
C17H16O2 252.1150; found 252.1147.
2-(1-Phenyl-1-(para-tolyl)ethyl)benzofuran (16). Following the
general procedure 2 for organocatalytic hydroarylation of alkene 1.
1
Isolated as a colorless oil (20.3 mg, 0.0649 mmol, 65%): H NMR
(400 MHz, chloroform-d) δ 7.51−7.45 (m, 1H), 7.43 (d, J = 8.1 Hz,
F
J. Org. Chem. XXXX, XXX, XXX−XXX