J. Barluenga et al.
elemental analysis calcd (%) for C14H19BrO: C 59.37, H 6.76; found: C
59.44, H 6.79.
and workup as described above yielded 7i (166 mg, 75%) as a colorless
oil. Rf =0.52 (hexane/ethyl acetate, 20:1); 1H NMR (CDCl3, 400 MHz):
d=7.12–7.07 (m, 2H), 4.73 (t, J=8.7 Hz, 1H), 4.10 (dd, J=8.7, 7.8 Hz,
1H), 3.61–3.51 (m, 1H), 2.41 (s, 3H), 1.42–1.38 (m, 2H), 0.40 (s,
9H) ppm; 13C NMR (CDCl3, 50 MHz): d=162.8, 133.2, 130.8, 128.9,
125.5, 119.2, 77.9, 36.0, 20.8, 18.7 (t, J=19.5 Hz), À1.2 ppm; LRMS
(70 eV, EI): m/z (%): 221 (97) [M]+, 75 (100); HRMS calcd for
C13H19DOSi: 221.1346; found: 221.1342.
2-(7-tert-Butyl-5-methyl-2,3-dihydrobenzofuran-3-yl)-N-phenylacetamide
(7d): Ether 6a (283 mg, 1 mmol) was treated with tBuLi (1.33 mL,
2 mmol) and TMEDA (0.33 mL, 2.2 mmol). Addition of phenyl isocya-
nate (131 mg, 1.1 mmol) and workup as described above yielded 7d
(197 mg, 61%) as a white solid. M.p. 132–1348C; 1H NMR (CDCl3,
400 MHz): d=7.69 (s, 1H), 7.51–7.45 (m, 2H), 7.33–7.27 (m, 2H), 7.15–
7.09 (m, 1H) 6.93 (s, 1H), 6.85 (s, 1H), 4.68 (t, J=9.1 Hz, 1H), 4.27 (dd,
J=9.1, 5.7 Hz, 1H), 3.94–3.84 (m, 1H), 2.74 (dd, J=15.0, 5.7 Hz, 1H),
2.59 (dd, J=15.0, 8.8 Hz, 1H), 2.27 (s, 3H), 1.36 (s, 9H) ppm; 13C NMR
(CDCl3, 101 MHz): d=169.5, 155.5, 137.4, 132.8, 129.7, 129.4, 128.9,
125.9, 124.4, 122.2, 120.1, 75.8, 42.5, 38.5, 33.9, 29.2, 20.9 ppm; LRMS
(70 eV, EI): m/z (%): 323 (18) [M]+, 135 (100); elemental analysis calcd
(%) for C21H25NO2: C 77.98, H 7.79, N 4.33; found: C 78.03, H 7.74, N
4.35.
2-(5-Methyl-7-trimethylsilyl-2,3-dihydrobenzofuran-3-yl)-N-phenylacet-
amide (7j): Ether 6c (299 mg, 1 mmol) was treated with tBuLi (1.33 mL,
2 mmol) and TMEDA (0.33 mL, 2.2 mmol). Addition of phenyl isocya-
nate (131 mg, 1.1 mmol) and workup as described above yielded 7j
(255 mg, 75%) as a white solid. M.p. 130–1328C; 1H NMR (CDCl3,
400 MHz): d=7.74 (s, 1H), 7.54–7.45 (m, 2H), 7.35–7.26 (m, 2H), 7.16–
7.09 (m, 1H), 7.04 (s, 1H), 6.99 (s, 1H), 4.66 (t, J=9.2 Hz, 1H), 4.24 (dd,
J=9.2, 5.8, 1H), 3.96–3.85 (m, 1H), 2.73 (dd, J=15.2, 6.2, 1H), 2.60 (dd,
J=15.2, 8.5, 1H), 2.27 (s, 3H), 0.30 (s, 9H) ppm; 13C NMR (CDCl3,
50 MHz): d=169.5, 162.7, 137.4, 133.9, 129.1, 128.9, 127.9, 125.9, 124.4,
120.1, 119.7, 75.9, 42.5, 38.3, 20.7, À1.3 ppm; LRMS (70 eV, EI): m/z (%):
339 (28) [M]+, 135 (100); elemental analysis calcd (%) for C20H25NO2Si:
C 70.75, H 7.42, N 4.13; found: C 70.67, H 7.38, N 4.09.
3-Deuteriomethyl-5,7-dimethyl-2,3-dihydrobenzofuran (7e): Ether 6b
(241 mg, 1 mmol) was treated with tBuLi (1.33 mL, 2 mmol) and
TMEDA (0.33 mL, 2.2 mmol). Addition of deuterium oxide (excess) and
workup as described above yielded 7e (101 mg, 62%) as a colorless oil.
Rf =0.22 (hexane/ethyl acetate, 20:1); 1H NMR (CDCl3, 400 MHz): d=
6.80 (s, 1H), 6.76 (s, 1H), 4.66 (t, J=8.7 Hz, 1H), 4.04 (dd, J=8.7,
7.6 Hz, 1H), 3.54–3.45 (m, 1H), 2.27 (s, 3H), 2.18 (s, 3H), 1.30–1.26 (m,
2H) ppm; 13C NMR (CDCl3, 101 MHz): d=155.8, 131.5, 129.7, 129.6,
121.6, 119.0, 78.2, 36.7, 20.7, 18.9 (t, J=19.5 Hz), 15.0 ppm; LRMS
(70 eV, EI): m/z (%): 163 (74) [M]+, 147 (100); HRMS (EI) calcd for
C11H13DO: 163.1106; found: 163.1110.
5-Methyl-3-tributylstannylmethyl-7-trimethylsilyl-2,3-dihydrobenzofuran
(7k): Ether 6c (299 mg, 1 mmol) was treated with tBuLi (1.33 mL,
2 mmol) and TMEDA (0.33 mL, 2.2 mmol). Addition of tributyltin chlo-
ride (358 mg, 1.1 mmol) and workup as described above yielded 7k
(351 mg, 69%) as a colorless oil. Rf =0.43 (hexane); 1H NMR (CDCl3,
400 MHz): d=7.08–7.03 (m, 2H), 4.71 (t, J=8.3 Hz, 1H), 4.01 (t, J=
8.3 Hz, 1H), 3.85–3.70 (m, 1H), 2.39 (s, 3H), 1.64–1.34 (m, 13H), 1.20
(dd, J=13.2, 9.2 Hz, 1H), 1.03–0.81 (m, 15H), 0.38 (s, 9H) ppm; 13C
NMR (CDCl3, 101 MHz): d=162.6, 133.1, 132.4, 128.9, 125.5, 119.2, 78.9,
39.9, 29.2, 27.4, 20.8, 14.5, 13.7, 9.3, À1.2 ppm; LRMS (70 eV, EI): m/z
(%): 453 (53) [MÀC4H9]+, 179 (100); elemental analysis calcd (%) for
C25H46OSiSn: C 58.94, H 9.10; found: C 58.85, H 9.04.
2-(5,7-Dimethyl-2,3-dihydrobenzofuran-3-yl)-1,1-diphenylethanol
(7 f):
Ether 6b (241 mg, 1 mmol) was treated with tBuLi (1.33 mL, 2 mmol)
and TMEDA (0.33 mL, 2.2 mmol). Addition of benzophenone (200 mg,
1.1 mmol) and workup as described above yielded 7 f (227 mg, 66%) as a
colorless oil. Rf =0.21 (hexane/ethyl acetate, 5:1); 1H NMR (CDCl3,
400 MHz): d=7.56–7.29 (m, 10H), 6.84–6.81 (m, 2H), 4.42 (t, J=9.0 Hz,
1H), 4.02 (t, J=9.0 Hz, 1H), 3.58–3.48 (m, 1H), 2.97 (dd, J=14.1,
2.1 Hz, 1H), 2.62 (dd, J=14.1, 10.3 Hz, 1H), 2.39 (s, 1H), 2.34 (s, 3H),
2.24 (s, 3H) ppm; 13C NMR (CDCl3, 101 MHz): d=155.7, 147.0, 146.2,
130.3, 129.8, 129.3, 128.2, 128.1, 127.2, 126.9, 126.0, 125.9, 121.5, 118.9,
77.9, 77.8, 47.2, 38.2, 20.6, 15.0 ppm; LRMS (70 eV, EI): m/z (%): 344
(17) [M]+, 146 (100); HRMS (EI) calcd for C24H24O2: 344.1776; found:
344.1776.
3-Bromomethyl-5-methyl-7-trimethylsilyl-2,3-dihydrobenzofuran
(7l):
Ether 6c (299 mg, 1 mmol) was treated with tBuLi (1.33 mL, 2 mmol)
and TMEDA (0.33 mL, 2.2 mmol). Addition of 1,2-dibromoethane
(207 mg, 1.1 mmol) and workup as described above yielded 7l (224 mg,
75%) as a white solid. M.p. 26–288C; 1H NMR (CDCl3, 400 MHz): d=
7.11–7.06 (m, 2H), 4.64 (t, J=9.3 Hz, 1H), 4.44 (dd, J=9.3, 5.4 Hz, 1H),
3.87–3.78 (m, 1H), 3.66 (dd, J=10.0, 4.6 Hz, 1H), 3.42 (t, J=10.0 Hz,
1H), 2.33 (s, 3H), 0.32 (s, 9H) ppm; 13C NMR (CDCl3, 101 MHz): d=
163.1, 134.7, 129.2, 126.1, 126.0, 120.2, 75.4, 44.6, 35.1, 20.7, À1.3 ppm;
LRMS (70 eV, EI): m/z (%): 300 (100) [M+2]+, 298 (92) [M]+; HRMS
(EI) calcd for C13H19BrOSi: 298.0389; found: 298.0390.
5,7-Dimethyl-3-phenylthiomethyl-2,3-dihydrobenzofuran (7g): Ether 6b
(241 mg, 1 mmol) was treated with tBuLi (1.33 mL, 2 mmol) and
TMEDA (0.33 mL, 2.2 mmol). Addition of diphenyl disulfide (237 mg,
1.1 mmol) and workup as described above yielded 7g (176 mg, 65%) as a
colorless oil. Rf =0.21 (hexane/ethyl acetate, 20:1); 1H NMR (CDCl3,
400 MHz): d=7.48–7.43 (m, 2H), 7.40–7.34 (m, 2H), 7.30–7.24 (m, 1H),
6.95 (s, 1H), 6.86 (s, 1H), 4.66 (t, J=9.0 Hz, 1H), 4.49 (dd, J=9.0,
5.7 Hz, 1H), 3.70–3.61 (m, 1H), 3.38 (dd, J=12.9, 4.8 Hz, 1H), 3.03 (dd,
J=12.9, 9.9 Hz, 1H), 2.34 (s, 3H), 2.26 (s, 3H) ppm; 13C NMR (CDCl3,
101 MHz): d=156.1, 135.5, 130.5, 129.5, 128.9, 128.2, 126.2, 122.1, 119.3,
75.7, 41.8, 38.5, 20.6, 15.0 ppm; LRMS (70 eV, EI): m/z (%): 270 (28)
[M]+, 147 (100); HRMS (EI) calcd for C17H18OS: 270.1078; found:
270.1076.
3-Methyl-7-trimethylsilyl-2,3-dihydrobenzofuran (7m): Ether 6d (285 mg,
1 mmol) was treated with tBuLi (1.33 mL, 2 mmol) and TMEDA
(0.33 mL, 2.2 mmol). Addition of water (excess) and workup as described
above yielded 7m (144 mg, 70%) as a colorless oil. Rf =0.56 (hexane/
ethyl acetate, 10:1); 1H NMR (CDCl3, 400 MHz): d=7.26–7.19 (m, 2H),
6.91 (t, J=7.3 Hz, 1H), 4.69 (t, J=8.5 Hz, 1H), 4.07 (t, J=8.5 Hz, 1H),
3.60–3.49 (m, 1H), 1.37 (d, J=6.9 Hz, 3H), 0.34 (s, 9H) ppm; 13C NMR
(CDCl3, 101 MHz): d=164.8, 132.9, 130.7, 124.8, 119.9, 119.7, 77.8, 36.1,
19.1, À1.2 ppm; LRMS (70 eV, EI): m/z (%): 206 (38) [M]+, 75 (100);
HRMS calcd for C12H18OSi: 206.1127; found: 206.1129.
3-Bromomethyl-5,7-dimethyl-2,3-dihydrobenzofuran (7h): Ether 6b
(241 mg, 1 mmol) was treated with tBuLi (1.33 mL, 2 mmol) and
TMEDA (0.33 mL, 2.2 mmol). Addition of 1,2-dibromoethane (207 mg,
1.1 mmol) and workup as described above yielded 7h (159 mg, 66%) as a
colorless oil. Rf =0.33 (hexane/ethyl acetate, 20:1); 1H NMR (CDCl3,
400 MHz): d=6.87 (s, 1H), 6.84 (s, 1H), 4.64 (t, J=9.2 Hz, 1H), 4.45 (dd,
J=9.2, 5.3 Hz, 1H), 3.87–3.79 (m, 1H), 3.63 (dd, J=10.0, 4.6 Hz, 1H),
3.39 (t, J=10.0 Hz, 1H), 2.28 (s, 3H), 2.20 (s, 3H) ppm; 13C NMR
(CDCl3, 101 MHz): d=156.4, 131.1, 129.7, 126.6, 122.2, 119.7, 75.6, 45.1,
35.1, 20.6, 15.0 ppm; LRMS (70 eV, EI): m/z (%): 242 (4) [M+2]+, 240
(4) [M]+, 147 (100); elemental analysis calcd (%) for C11H13BrO: C
54.79, H 5.43; found: C 54.84, H 5.40.
2-(7-Trimethylsilyl-2,3-dihydrobenzofuran-3-yl)-N-phenylacetamide (7n):
Ether 6d (285 mg, 1 mmol) was treated with tBuLi (1.33 mL, 2 mmol)
and TMEDA (0.33 mL, 2.2 mmol). Addition of phenyl isocyanate
(131 mg, 1.1 mmol) and workup as described above yielded 7n (228 mg,
1
70%) as a white solid. M.p. 129–1318C; H NMR (CDCl3, 400 MHz): d=
7.81 (s, 1H), 7.51–7.43 (m, 2H), 7.33–7.23 (m, 3H), 7.19–7.08 (m, 2H),
6.86 (t, J=7.3 Hz, 1H), 4.68 (t, J=9.1 Hz, 1H), 4.24 (dd, J=9.1, 5.8 Hz,
1H), 3.98–3.88 (m, 1H), 2.72 (dd, J=15.1, 6.2 Hz, 1H), 2.59 (dd, J=15.1,
8.5 Hz, 1H), 0.32 (s, 9H) ppm; 13C NMR (CDCl3, 50 MHz): d=169.5,
164.7, 137.4, 133.7, 128.9, 127.7, 125.2, 124.5, 120.2, 120.1, 75.8, 42.5, 38.2,
À1.3 ppm; LRMS (70 eV, EI): m/z (%): 325 (13) [M]+, 135 (100); ele-
mental analysis calcd (%) for C19H23NO2Si: C 70.11, H 7.12, N 4.30;
found: C 70.17, H 7.18, N 4.25.
3-Deuteriomethyl-5-methyl-7-trimethylsilyl-2,3-dihydrobenzofuran (7i):
Ether 6c (299 mg, 1 mmol) was treated with tBuLi (1.33 mL, 2 mmol)
and TMEDA (0.33 mL, 2.2 mmol). Addition of deuterium oxide (excess)
5404
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2005, 11, 5397 – 5407