M. C. Elliott, N. N. E. El Sayed, J. S. Paine
FULL PAPER
1.9 Hz, Ha), 4.48 (app. dd, JH,H = 3.2, JH,H = 1.3 Hz, 1 H, Hf),
with MgSO4, filtered and concentrated under reduced pressure to
afford a pale yellow solid. Purification by flash chromatography
3
4
2
3
3.91 (d, JH,H = 11.4 Hz, 1 H, Hi), 3.69 (q, JH,H = 6.4 Hz, 1 H,
Hg), 3.57 (d, JH,H = 11.4 Hz, 1 H, Hj), 3.56–3.51 (m, 1 H, Hh), (eluting with ethyl acetate/hexane, 1:9) afforded compound 3c as a
2
2.32 (app. ddt, 2JH,H = 19.3, 3JH,H = 6.0, 3JH,H and 4JH,H = 2.7 Hz,
1 H, Hc), 2.24–2.16 (m, 1 H, Hd), 2.01–1.96 (m, 1 H, He), 1.67
colourless solid (85 mg, 28%), compound 6 as a pale yellow oil
(30 mg, 9%) and compound 2c as a pale yellow solid (74 mg, 24%),
respectively.
3
2
(app. nonet, JH,H = 6.6 Hz, 1 H, Hm), 1.53 (app. ddd, JH,H
=
13.9, 3JH,H = 8.4, 3JH,H = 6.4 Hz, 1 H, Hk), 1.16–1.10 (m, 1 H, Hl),
[(1RS,3SR,3aSR,7aSR)-3-(2-Bromophenyl)-6-chloro-1,3,3a,6,7,7a-
hexahydro-1-phenylisobenzofuran-4-yl]methanol (2c): Pale yellow so-
3
3
1.08 (d, JH,H = 6.4 Hz, 3 H, CH3CHg), 0.84 [d, JH,H = 6.4 Hz, 3
3
H, one of (CH3)2CH], 0.83 [d, JH,H = 6.4 Hz, 3 H, one of
lid (74 mg, 24%) m.p. 50 –52 °C. IR (CH Cl ): ν = 3426 (broad),
˜
(CH3)2CH] ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ = 130.9
(CH), 121.9 (CH), 79.1 (CH), 76.4 (CH), 63.5 (CH and CH2), 45.9
(C), 42.0 (CH2), 40.2 (CH), 24.6 (CH), 23.2 (CH2), 23.0 (CH3),
22.5 (CH3), 16.2 (CH3) ppm. MS (CI): m/z (%) = 276 (100) [M +
NH4+], 240 (50), 223 (22), 179 (23). HRMS (ES+) C14H2735ClNO2
[MNH4+] 276.1725; found 276.1723. Hydrogen connectivity fully
supported by 1H-1H COSY NMR spectroscopy. Diagnostic
NOESY correlations {Hf,Hg} {Hf,Hh} {Hg,Hh}.
2
2
3061, 3021, 2929, 1732, 1567, 1470, 1367, 1267, 1206, 1121,
1
3
916 cm–1. H NMR (400 MHz, CDCl3, 25 °C): δ = 7.82 (d, JH,H
= 7.8 Hz, 2 H, 2ϫaromatic CH), 7.14 (m, 3 H, 3ϫaromatic CH),
7.10–7.05 (m, 2 H, 2ϫaromatic CH), 7.05–6.99 (m, 2 H, 2ϫaro-
3
3
matic CH), 6.14 (d, JH,H = 7.4 Hz, 1 H, Ha), 5.36 (d, JH,H
=
5.0 Hz, 1 H, Hg), 5.25 (d, JH,H = 9.2 Hz, 1 H, Hh), 3.53 (app. t,
3
3JH,H = 5.7 Hz, 1 H, Hf), 3.40–3.32 (m, 1 H, He), 3.32–3.26 (m, 1
H, Hb), 2.93 and 2.84 (AB quartet, JH,H = 13.5 Hz, 2 H, Hi and
2
Hj), 2.01–1.89 (m, 2 H, Hc and Hd) ppm. 13C NMR (100 MHz,
CDCl3, 25 °C): δ = 139.0 (C), 136.4 (C), 135.9 (C), 132.6 (CH),
132.2 (CH), 130.9 (CH), 130.8 (CH), 129.1 (CH), 128.6 (CH), 127.6
(CH), 127.6 (CH), 127.0 (CH), 126.7 (CH), 121.3 (C), 83.6 (CH),
77.6 (CH), 64.7 (CH2), 44.1 (CH), 37.7 (CH), 35.1 (CH), 29.6
(CH2) ppm. MS (ES+): m/z (%) = 402 (86) [MNH4+ – HCl, (81Br)],
400 (89), 367 (84), 365 (100). HRMS (ES+) C21H2379BrNO2
(1SR,3SR,3aSR,7aSR)-1-Isobutyl-1,3,3a,6,7,7a-hexahydro-3-meth-
ylisobenzofuran-4-carbaldehyde (4e): Yellow oil (70 mg, 37%). IR
(neat): ν = 2954, 1684, 1642, 1466, 1371, 1093 cm–1 1H NMR
.
˜
(400 MHz, CDCl3, 25 °C): δ = 9.39 (s, 1 H, Ha), 6.94 (app. d, 3JH,H
= 5.1 Hz, 1 H, Hb), 4.31 (app. dq, JH,H = 9.9, JH,H = 6.4 Hz, 1
3
3
3
3
3
H, Hi), 3.86 (ddd, JH,H = 7.3, JH,H = 6.1, JH,H = 4.0 Hz, 1 H,
3
2
Hj), 3.16 (app. t, JH,H = 8.1 Hz, 1 H, Hh), 2.45 (app. dtd, JH,H
=
20.0, 3JH,H = 4.2, 3JH,H = 1.1 Hz, 1 H, Hc), 2.26–2.12 (m, 1 H, Hd),
1.90 (app. ddt, 3JH,H = 13.1, 3JH,H = 6.9, 3JH,H = 4.0 Hz, 1 H, Hg),
+
[MNH4 – HCl] 400.0912; found 400.0909. Hydrogen connectivity
fully supported by 1H-1H COSY NMR spectroscopy. Diagnostic
NOESY correlations {He,Hf} {He,Hg} {He,Hh} {Hf,Hg} {Hf,Hh}.
1.72–1.59 (m, 2 H, He and Hm), 1.47 (app. dt, JH,H = 13.6, JH,H
= 7.2 Hz, 1 H, Hk), 1.41–1.27 (m, 2 H, Hf and Hl), 0.91–0.84 (m,
9 H, m, 3ϫCH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ =
194.5 (CH), 152.7 (CH), 141.0 (C), 78.7 (CH), 74.5 (CH), 39.4
(CH), 39.2 (CH), 38.8 (CH2), 25.7 (CH2), 25.5 (CH), 23.3 (CH3),
22.8 (CH3), 19.8 (CH3), 19.3 (CH2) ppm. MS (CI): m/z (%) = 222
(1) [M+], 178 (26), 136 (59), 107 (81), 91 (100). HRMS (EI)
C14H22O2 [M+] 222.1611; found 222.1623. Hydrogen connectivity
fully supported by 1H-1H COSY NMR spectroscopy. Diagnostic
NOESY correlations {Hg,Hh} {Hg,Hj} {Hh,Hi} {Hh,Hj} {Hi,Hj}.
2
3
[(1RS,2SR,4SR,5RS,9RS)-2-(2-Bromophenyl)-9-chloro-4-phenyl-3-
oxabicyclo[3.3.1]non-7-en-1-yl]methanol (3c): Colourless solid
(85 mg, 28%), m.p. 70–72 °C. IR (CH Cl ): ν = 3466, 3061, 3027,
˜
2
2
2924, 1472, 1266, 1122, 1071, 1030, 751 cm–1. 1H NMR (400 MHz,
3
4
CDCl3, 25 °C): δ = 7.59 (dd, JH,H = 7.9, JH,H = 1.6 Hz, 1 H,
aromatic CH), 7.49 (dd, 3JH,H = 8.0, 4JH,H = 0.9 Hz, 1 H, aromatic
CH), 7.32–7.24 (m, 5 H, 5ϫaromatic CH), 7.23–7.17 (m, 1 H, aro-
matic CH), 7.12 (app. td, 3JH,H = 7.7, 4JH,H = 1.7 Hz, 1 H, aromatic
3
3
CH), 5.99 (app. dt, JH,H = 9.9, JH,H = 3.4 Hz, 1 H, Hb), 5.16 (s,
1 H, Hg), 4.92 (broad resonance, 2 H, Hh and Hf), 4.87 (app. dd,
3JH,H = 9.9, 4JH,H = 1.6 Hz, 1 H, Ha), 3.66 (dd, 2JH,H = 12.3, 3JH,H
Prins Cyclisation of Benzaldehyde Acetal 1c at –78 °C for 2 h
2
3
= 7.6 Hz, 1 H, Hi), 3.31 (dd, JH,H = 12.3, JH,H = 4.8 Hz, 1 H,
Hj), 2.52–2.47 (m, 1 H, He), 2.19 (app. ddt, JH,H = 19.4, JH,H
=
2
3
6.7, JH,H and JH,H = 2.6 Hz, 1 H, Hc), 2.14–2.09 (m, 1 H, OH),
2.01–1.91 (m, 1 H, Hd) ppm. 13C NMR (100 MHz, CDCl3, 25 °C):
δ = 139.6 (C), 137.5 (C), 132.3 (CH), 131.6 (CH), 130.6 (CH), 129.8
(CH), 128.3 (2ϫCH), 127.4 (CH), 127.3 (CH), 125.6 (2ϫ CH),
123.5 (C), 121.7 (CH), 82.4 (CH), 80.9 (CH), 63.2 (CH2), 62.7
(CH), 46.6 (C), 41.1 (CH), 23.2 (CH2) ppm. Hydrogen connectivity
fully supported by 1H-1H COSY NMR spectroscopy. Structure and
stereochemistry confirmed by single-crystal X-ray diffraction.
3
4
[(1RS,3SR,3aRS,7RS,7aSR)-3-(2-Bromophenyl)-7-chloro-1,6,7,7a-
tetrahydro-1-phenylisobenzofuran-3a-yl]methanol (6): Pale yellow oil
(30 mg, 9%). IR (neat): ν = 3450, 3065, 3032, 2931, 1470, 1439,
˜
1
1374, 1269, 1206, 1067, 1020, 909, 733 cm–1. H NMR (400 MHz,
3
4
CDCl3, 25 °C): δ = 7.54 (dd, JH,H = 7.9, JH,H = 1.6 Hz, 1 H,
aromatic CH), 7.49 (dd, 3JH,H = 8.0, 4JH,H = 0.9 Hz, 1 H, aromatic
3
CH), 7.42 (d, JH,H = 7.4 Hz, 2 H, 2ϫaromatic CH), 7.35–7.22
(m, 4 H, 4ϫaromatic CH), 7.12 (app. td, JH,H = 7.6, JH,H
3
4
Titanium tetrachloride (0.16 mL, 1.5 mmol) was carefully added
to a cooled (–78 °C) solution of benzaldehyde acetal 1c (280 mg,
0.73 mmol) in dry CH2Cl2 (10 mL) under nitrogen. The resulting
mixture was stirred at this temperature for 15 min, then carefully
quenched with saturated aqueous NaHCO3 solution (10 mL). The
phases were separated and the organic material extracted into
CH2Cl2 (2ϫ20 mL). The combined organic extracts were dried
=
=
3
3
1.6 Hz, 1 H, aromatic CH), 5.66 (app. dt, JH,H = 10.2, JH,H
4.1 Hz, 1 H, Hb), 5.25 (d, JH,H = 7.5 Hz, 1 H, Hh), 5.23 (s, 1 H,
3
Hg), 4.81 (app. dt, JH,H = 10.2, JH,H = 1.7 Hz, 1 H, Ha), 4.04–
3
4
4.01 (m, 1 H, He), 3.89 and 3.83 (AB quartet, JH,H = 11.3 Hz, 2
2
H, Hi and Hj), 3.23 (app. t, 3JH,H = 7.0 Hz, 1 H, Hf), 2.20–2.06 (m,
2 H, Hc and Hd) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ =
800
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Eur. J. Org. Chem. 2007, 792–803