S. Ponnala, W. W. Harding
FULL PAPER
Compound 13e: Yield 0.031 g (73.5%), colorless oil. Rf = 0.60 (silica H), 7.46 (d, J = 9.0 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 14.6,
gel, hexanes/EtOAc, 6:4). 1H NMR (CDCl3): δ = 1.23 (m, 3 H),
2.79 (m, 1 H), 2.98 (m, 1 H), 3.40 (m, 1 H), 3.74 (s, 3 H), 3.89 (s,
3 H), 4.16 (m, 3 H), 6.49 (br. s, 1 H), 6.55 (s, 1 H), 6.67 (s, 1 H),
28.6, 39.8, 55.3, 55.9, 57.2, 61.7, 110.7, 111.3, 113.7, 114.9, 115.1,
121.4, 126.0, 127.9, 133.6, 144.3, 145.7, 156.0, 158.9 ppm. HRMS
(ESI): calcd. for C20H23BrNO5 [M
+
H]+ 436.0681; found
7.05 (br. s, 1 H), 7.12 (m, 1 H), 7.19 (m, 1 H), 7.63 (d, J = 7.9 Hz, 436.0676.
1 H) ppm. 13C NMR (CDCl3): δ = 14.6, 28.2, 39.3, 55.9 (ϫ2), 57.3,
61.6, 110.5, 111.3 (ϫ2), 126.7, 127.2, 127.6, 128.8, 130.0, 133.1,
147.7, 148.03, 148.04, 155.9 ppm. HRMS (ESI): calcd. for
C20H23BrNO4 [M + H]+ 420.0732; found 420.0728.
Compound 13l: Yield 0.034 g (73%), colorless oil. Rf = 0.35 (silica
gel, hexanes/EtOAc, 6:4). 1H NMR (CDCl3): δ = 1.20 (m, 3 H),
2.25 (s, 1 H), 2.76 (m, 1 H), 2.96 (m, 1 H), 3.39 (m, 1 H), 3.67 (s,
3 H), 3.86 (s, 6 H), 4.14 (q, J = 6.5 Hz, 2 H), 4.28 (br. s, 1 H), 6.29
(br. s, 1 H), 6.55 (s, 1 H), 6.56 (s, 1 H), 6.63 (s, 1 H), 7.03 (s, 1
H) ppm. 13C NMR (CDCl3): δ = 14.6, 28.8, 39.9, 55.90, 55.95, 56.1,
57.0, 61.6, 110.5 (ϫ2), 112.2, 113.6, 114.6, 115.4, 125.9, 128.1,
144.3, 145.6, 148.5, 148.6, 155.9 ppm. HRMS (ESI): calcd. for
C21H25BrNO6 [M + H]+ 466.0787; found 466.0785.
Compound 13f: Yield 0.028 g (67%), white solid. Rf = 0.40 (silica
gel, hexanes/EtOAc, 6:4). M.p. 129–131 °C. 1H NMR (CDCl3): δ
= 1.30 (m, 3 H), 2.80 (m, 1 H), 2.94 (m, 1 H), 3.41 (m, 1 H), 3.77
(s, 3 H), 4.14 (m, 3 H), 5.68 (s, 1 H), 6.49 (br. s, 1 H), 6.54 (s, 1
H), 6.77 (m, 2 H), 6.87 (m, 1 H), 7.60 (dd, J = 5.5, 8.5 Hz, 1
H) ppm. 13C NMR (CDCl3): δ = 14.6, 28.0, 39.5, 55.9, 57.4, 61.7,
109.7, 114.5, 115.9, 116.1, 117.2, 117.9, 125.9, 127.4, 134.2, 144.9,
145.5, 155.9, 161.9 ppm. 19F NMR (CDCl3): δ = –113.5 (d, J =
360 Hz) ppm. HRMS (ESI): calcd. for C19H20BrFNO4 [M + H]+
420.0481; found 420.0477.
Compound 13m: Yield 0.042 g (82%), colorless oil. Rf = 0.62 (silica
gel, hexanes/EtOAc, 6:4). 1H NMR (CDCl3): δ = 1.13 (m, 3 H),
2.62 (m, 1 H), 3.08 (m, 1 H), 3.34 (s, 3 H), 3.51 (m, 1 H), 3.62 (s,
3 H), 3.81 (s, 3 H), 3.83 (s, 3 H), 3.86 (s, 3 H), 4.07 (m, 2 H), 4.38
(br. s, 1 H), 6.14 (s, 1 H), 6.33 (br. s, 1 H), 6.75 (d, J = 8.5 Hz, 1
H), 7.34 (d, J = 8.5 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 14.6,
23.3, 39.9, 55.8, 55.9, 57.1, 59.6, 60.90, 60.94, 61.3, 105.7, 112.7,
116.8, 121.3, 127.6, 130.9, 136.8, 140.7, 148.4, 150.6, 151.6, 152.9,
156.1 ppm. HRMS (ESI): calcd. for C23H29BrNO7 [M + H]+
510.1049; found 510.1048.
Compound 13g: Yield 0.030 g (68%), white solid. Rf = 0.38 (silica
gel, hexanes/EtOAc, 6:4). M.p. 105–107 °C. 1H NMR (CDCl3): δ
= 1.22 (m, 3 H), 2.77 (m, 1 H), 2.93 (m, 1 H), 3.42 (m, 1 H), 3.71
(s, 3 H), 3.77 (s, 3 H), 4.15 (m, 3 H), 5.56 (m, 1 H), 6.39 (br. s, 1
H), 6.56 (s, 1 H), 6.61 (br. s, 1 H), 6.69 (dd, J = 3.5, 8.5 Hz, 1 H),
6.74 (s, 1 H), 7.51 (d, J = 8.5 Hz, 1 H) ppm. 13C NMR (CDCl3): δ
= 14.6, 28.0, 39.4, 55.3, 55.9, 57.5, 61.6, 109.9, 113.8, 114.3 (ϫ2),
115.7, 126.5 (ϫ2), 127.4 (ϫ2), 133.5, 143.8, 145.4, 155.9 ppm.
HRMS (ESI): calcd. for C20H23BrNO5 [M + H]+ 436.0681; found
436.0679.
Compound 13n: Yield 0.038 g (80%), white solid. Rf = 0.67 (silica
gel, hexanes/EtOAc, 6:4). M.p. 78–80 °C. 1H NMR (CDCl3): δ =
1.23 (m, 3 H), 2.81 (m, 2 H), 3.35 (m, 1 H), 3.71 (s, 3 H), 3.73 (s,
3 H), 3.88 (s, 3 H), 3.91 (s, 3 H), 4.16 (m, 3 H), 6.41 (br. s, 2 H),
6.59 (br. s, 1 H), 6.70 (dd, J = 3.0, 8.5 Hz, 1 H), 7.53 (d, J = 8.5 Hz,
1 H) ppm. 13C NMR (CDCl3): δ = 14.6, 22.4, 39.2, 55.4, 55.9,
57.4, 60.7, 60.8, 61.6, 106.5, 113.6, 114.8, 115.9, 116.2, 121.1, 130.6,
133.6, 140.9, 150.9, 152.0, 155.9, 158.9 ppm. HRMS (ESI): calcd.
for C22H27BrNO6 [M + H]+: 480.0944; found 480.0939.
Compound 13h: Yield 0.028 g (70%), colorless oil. Rf = 0.39 (silica
gel, hexanes/EtOAc, 6:4). 1H NMR (CDCl3): δ = 1.20 (m, 3 H),
2.71 (m, 1 H), 2.90 (m, 1 H), 3.34 (m, 1 H), 3.71 (s, 3 H), 4.14 (m,
3 H), 5.70 (s, 1 H), 6.43 (br. s, 1 H), 6.50 (s, 1 H), 6.72 (s, 1 H),
7.02 (br. s, 1 H), 7.09 (m, 1 H), 7.17 (m, 1 H), 7.60 (d, J = 8.5 Hz,
1 H) ppm. 13C NMR (CDCl3): δ = 14.6, 28.0, 38.4, 55.9, 57.4, 61.6,
109.9, 114.3 (ϫ2), 124.2, 126.7, 127.5, 128.7, 129.8, 130.8, 133.1,
144.6, 145.4, 155.9 ppm. HRMS (ESI): calcd. for C19H21BrNO4 [M
+ H]+ 408.0630; found 408.0630.
Compound 15: 1:1 Mixture of rotamers (signals for one rotamer
reported). Yield 0.037 g (83%), colorless oil. Rf = 0.7 (silica gel,
hexanes/EtOAc, 6:4). 1H NMR (CDCl3): δ = 1.29 (m, 3 H), 2.69
(m, 1 H), 2.96 (m, 1 H), 3.13 (m, 1 H), 3.77 (s, 3 H), 3.84 (s, 3 H),
3.90 (s, 3 H), 4.30 (m, 2 H), 4.38 (m, 1 H), 6.51 (s, 1 H), 6.76 (m,
4 H), 7.20 (m, 1 H) ppm. 13C NMR (CDCl3): δ = 14.8, 28.2, 55.1,
56.1, 57.2, 57.4, 60.6, 61.7, 111.6, 112.3, 114.4, 119.5, 120.6, 127.5,
129.1, 132.5, 142.3, 145.0, 152.3, 155.0, 159.1 ppm. HRMS (ESI):
calcd. for C21H25BrNO5 [M + H]+: 450.0838; found 450.0835.
Compound 13i: Yield 0.026 g (62%), colorless oil. Rf = 0.40 (silica
gel, hexanes/EtOAc, 6:4). 1H NMR (CDCl3): δ = 1.21 (m, 3 H),
2.82 (m, 1 H), 2.95 (m, 1 H), 3.42 (dd, J = 10.5, 10.5 Hz, 1 H),
3.89 (s, 3 H), 4.14 (m, 3 H), 5.57 (s, 1 H), 6.36 (br. s, 1 H), 6.58 (s,
1 H), 6.66 (s, 1 H), 6.76 (br. s, 1 H), 6.84 (m, 1 H), 7.56 (dd, J =
5.5, 9.0 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 14.6, 28.6, 39.8,
55.9, 57.2, 61.8, 110.5, 113.5, 115.9, 116.1, 126.3, 127.5, 134.3,
144.0, 146.14, 146.14, 156.3, 160.9, 163.2 ppm. 19F NMR (CDCl3):
δ = –114.2 (d, J = 250 Hz) ppm. HRMS (ESI): calcd. for
C19H20BrFNO4 [M + H]+ 424.0553; found 424.0553.
Compound 18a: Mixture of rotamers (signals for one rotamer re-
ported). Yield 0.080 g (35.7%), colorless oil. Rf = 0.2 (silica gel,
hexanes/EtOAc, 6:4). 1H NMR (CDCl3): δ = 1.55 (m, 9 H), 2.64
(m, 1 H), 2.93 (m, 1 H), 3.05 (m, 1 H), 3.83 (m, 1 H), 3.85 (s, 3
H), 3.89 (s, 3 H), 6.63 (s, 1 H), 6.74 (m, 1 H), 7.06 (m, 2 H), 8.51
(m, 2 H) ppm. 13C NMR (CDCl3): δ = 28.4, 37.3, 38.4, 55.8, 56.1,
60.6, 76.8, 77.1, 80.5, 112.0, 119.0, 119.5, 122.7, 126.5, 126.6, 132.8,
145.3, 149.8, 150.1, 152.8, 154.8 ppm. HRMS (ESI): calcd. for
C21H26BrN2O4 [M + H]+ 449.0998; found 449.0996.
Compound 13j: Yield 0.032 g (70%), white solid. Rf = 0.36 (silica
gel, hexanes/EtOAc, 6:4). M.p. 161–163 °C. 1H NMR (CDCl3): δ
= 1.24 (m, 3 H), 2.77 (m, 1 H), 2.94 (m, 1 H), 3.39 (m, 1 H), 3.89
(s, 3 H), 4.15 (m, 3 H), 5.48 (s, 1 H), 5.94 (m, 2 H), 6.33 (br. s, 1
H), 6.55 (m, 2 H), 6.64 (s, 1 H), 7.05 (s, 1 H) ppm. 13C NMR
(CDCl3): δ = 14.2, 28.6, 39.7, 55.9, 57.1, 61.7, 101.8 (ϫ2), 109.2,
110.7 (ϫ2), 112.6, 113.6, 114.5, 126.0, 136.2, 144.3, 145.8, 147.4,
155.9 ppm. HRMS (ESI): calcd. for C20H21BrNO6 [M + H]+
452.0529; found 452.0527.
Compound 18b: Yield 0.034 g (82%), colorless oil. Rf = 0.2 (silica
gel, hexanes/EtOAc, 6:4). 1H NMR (CDCl3): δ = 1.18 (m, 3 H),
2.93 (m, 2 H), 3.46 (m, 1 H), 3.73 (s, 3 H), 3.86 (s, 3 H), 4.12 (m,
3 H), 6.36 (br. s, 1 H), 6.55 (d, J = 4.5 Hz, 1 H), 6.66 (d, J = 4.5 Hz,
1 H), 7.03 (br. s, 1 H), 8.37 (s, 1 H), 8.75 (s, 1 H) ppm. 13C NMR
(CDCl3): δ = 14.5, 28.3, 40.0, 55.9, 56.7, 61.9, 109.9, 111.44, 122.3,
125.4, 126.7, 148.2, 149.1, 153.4, 156.5 ppm. HRMS (ESI): calcd.
for C19H22BrN2O4 [M + H]+ 421.0685; found 421.0687.
Compound 13k: Yield 0.032 g (73%), colorless oil. Rf = 0.38 (silica
gel, hexanes/EtOAc, 6:4). 1H NMR (CDCl3): δ = 1.18 (m, 3 H),
2.75 (m, 1 H), 2.92 (m, 1 H), 3.40 (m, 1 H), 3.66 (s, 3 H), 3.85 (s,
3 H), 4.11 (m, 3 H), 5.70 (br. s, 1 H), 6.33 (br. s, 1 H), 6.65 (m, 4
Synthesis of Compound 12. Procedure for Microwave-Assisted Direct
Arylation Reaction: In a microwave reaction vial, dihydroisoquin-
1112
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Eur. J. Org. Chem. 2013, 1107–1115