Beilstein Journal of Organic Chemistry 2009, 5, No. 9.
aqueous phase was extracted with Et2O (3 × 100 mL) and the and the reaction stirred for 3 hours at rt. The reaction was
combined organic phases dried (MgSO4). After removal of the poured into saturated aqueous NH4Cl solution (100 mL) and
solvent, the residue was purified by chromatography (5% Et2O/ extracted with Et2O (3 × 100 mL). The combined organic layers
hexane) followed by trituration of the yellow semi-solid with were dried (MgSO4) and concentrated before purification by
petrol gave (Sp)-6 as a white solid (1.0 g, 41.0%); mp = 53 °C; chromatography (1% Et2O/hexane) gave (Sp)-2 as a white solid
[
α]D + 89.5 (c 1, CHCl3) (assumed 80% ee see text); νmax (film) (0.14 g, 32%); mp = 144–146 °C; [α]D + 164.0 (c 1, CHCl3)
2
1
957, 2926, 2894, 1471, 1455, 1433, 1411, 1389, 1362 and (assumed 80% ee see text); νmax (film) 3011, 2929, 2848, 2558,
165 cm−1; δH (500 MHz, CDCl3) 6.68 (1H, s, H-5), 6.68 (1H, 1587, 1548, 1499, 1480, 1449, 1432, 1411, 1060, 938, 897, 849,
d, J = 10.0 Hz, H-13), 6.54 (2H, dd, J = 8.0, 3.5 Hz, H-7, H-8), 804 and 791 cm−1; δH (500 MHz, CDCl3) 7.21 (1H, d, J = 7.5
.50 (2H, s, H-15, H-16), 6.45 (1H, d, J = 8.0 Hz, 12-H), 3.84 Hz, H-13), 6.57 (1H, d, J = 7.5 Hz, H-8), 6.47 (1H, d, J = 7.5
1H, t, J = 11.0 Hz, H-2 endo), 3.20–3.14 (1H, m, H-1 endo), Hz, H-7), 6.43 (1H, d, J = 7.5 Hz, H-12), 6.40 (2H, t, J = 7.5
.12–2.97 (5H, m, H-1 exo, 2 × H-9, 2 × H-10), 2.83 (1H, ddd, Hz, H-15, H-16), 6.22 (1H, s, H-5), 3.41 (1H, t, J = 12.0 Hz,
6
(
3
J = 12.0, 5.5, 3.7 Hz, H-2 exo), 1.17 (9H, s, t-Bu); δC (125 H-2 endo), 3.26 (1H, ddd, J = 13.0, 6.0, 3.9 Hz, H-1 endo), 3.13
MHz, CDCl3) 145.7 (C), 144.4 (C), 139.9 (C), 139.4 (C), 139.1 (1H, s, S-H), 3.11–3.01 (4H, m, 2 × H-9, 2 × H-10), 2.90–2.87
(
(
(
[
(
C), 134.2 (CH), 133.5 (CH), 133.0 (CH), 132.9 (CH), 132.8 (1H, t, J = 9.0 Hz, H-1 exo), 2.83–2.77 (1H, m, H-2 exo); δC
CH), 132.5 (CH), 131.0 (CH), 46.3 (C), 35.4 (CH2), 35.4 (125 MHz, CDCl3) 140.4 (C), 139.3 (C), 139.1 (C), 138.5 (C),
CH2), 34.8 (CH2), 34.7 (CH2), 30.9 (CH3); m/z (EI+) 296 135.8 (CH), 134.8 (CH), 133.4 (CH), 132.8 (CH), 131.9 (CH),
M]+, 240 [M – t-Bu]+, 207 [M − St-Bu]+, 136, 104, 91, 78 131.5 (CH), 130.5 (CH), 127.7 (CH), 35.4 (CH2), 34.9 (CH2),
Found: [M]+, 296.1591. C20H24S requires [M]+, 296.1593). 34.6 (CH2), 33.1 (CH2); m/z (EI+) 240 [M]+, 207 [[2.2]paracyc-
lophane]+, 136, 104, 91, 78 (Found: [M]+, 240.0969. C16H16S
(Sp)-(+)-Thioacetic acid S-[2.2]paracyclo-
requires [M]+, 240.0967).
phan-4-yl ester [(Sp)-7]
Boron tribromide (0.36 mL, 3.77 mmol, 1.1 equiv) was added
(Rp,RS)-(–)-4-tert-Butylsulfinyl-5-amino[2.2]-
to a solution of (Sp)-(+)-4-t-butylsulfanyl[2.2]paracyclophane paracyclophane [(Rp,RS)-8]
Sp)-6 (1.0 g, 3.43 mmol, 1.0 equiv) and acetyl chloride (1.7 To a solution of (Rp,RS)-(–)-4-t-butylsulfinyl[2.2]paracyclo-
(
mL, 24.01 mmol, 7.0 equiv) in toluene (34.3 mL) at rt. The phane [(Rp,RS)-5] (5.80 g, 18.6 mmol, 1.0 equiv) in THF (350
reaction was stirred for 1 hour then poured into a solution of ice mL) at 0 °C was added n-BuLi (2.5M in hexanes; 16.5 mL,
cold saturated aqueous NH4Cl (200 mL). Aqueous phase was 41.25 mmol, 2.2 equiv) dropwise over 30 min to give an orange
extracted with Et2O (3 × 50 mL). The combined organic phase solution. After 1 h tosyl azide (9.20 g, 46.70 mmol, 2.5 equiv)
was washed with aqueous Na2S2O3 (10% w/v) (3 × 50 ml), was added and the reaction warmed to rt over 18 h. NaBH4
dried (MgSO4) and concentrated. Purification by chromato- (6.45 g, 171 mmol, 9 equiv) and tetra-n-butyl ammonium
graphy (10% Et2O/hexane) afforded (Sp)-7 as a white solid iodide (6.31 g, 17.1 mmol, 0.9 equiv) were added and the reac-
(
(
0.53 g, 55%); mp = 134–136 °C; [α]D + 84.3 (c 1, CHCl3) tion stirred for a further 24 h at rt whereupon a further portion
assumed 80% ee see text); νmax (film) 2920, 2850, 1694, 1498, of NaBH4 (2.80 g, 74.0 mmol, 4.0 equiv) was added. After
1
476, 1447, 1432, 1408, 1113, 954, 906, 850 and 792 cm−1; δH further stirring at rt for 5 days the reaction was poured into
(
500 MHz, CDCl3) 6.68 (1H, d, J = 8.0 Hz, H-13), 6.60 (2H, s, saturated aqueous NH4Cl (250 mL) causing effervescence. The
H-15, H-16), 6.52 (3H, m, H-5, H-7, H-8), 6.42 (1H, d, J = 7.5 aqueous phase was extracted with Et2O (500 mL + 200 mL) and
Hz, H-12), 3.41–3.35 (1H, m, H-2 endo), 3.13–2.97 (5H, m, the combined organic extracts dried (MgSO4) and the solvent
H-1 endo, 2 × H-9, 2 × H-10), 2.99 (1H, t, J = 10.2 Hz, H-1 removed. The residue was purified by chromatography (neutral-
exo), 2.92–2.86 (1H, m, H-2 exo), 2.36 (3H, s, Me); δC (125 ized silica gel 40% Et2O/n-heptane) to yield 8 as a pale yellow
MHz, CDCl3) 190.7 (CO), 143.1 (C), 140.4 (C), 139.4 (C), solid powder, which was recrystalised from CHCl3 / heptane
1
1
3
39.1 (C), 135.1 (CH), 135.0 (CH), 134.5 (CH), 133.2 (CH), (4.00 g, 66%); mp = 130–132 °C; [α]D −118.0 (c 1, CHCl3)
33.1 (CH), 132.3 (CH), 130.2 (CH), 129.2 (CH), 35.4 (CH2), (assumed 80% ee see text); νmax (film) 3430, 3055, 2987, 1637,
4.9 (CH2), 34.6 (CH2), 34.4 (CH2), 30.2 (CH3); m/z (EI+) 282 1421, 1265, 896, 739 and 705 cm−1; δH (500 MHz, CDCl3)
[
M]+, 240 [M+H-Ac]+, 207 [[2.2]paracyclophane]+, 178, 136, 7.15 (1H, d, J = 8.0 Hz, H-13), 6.89 (1H, d, J = 7.5 Hz, H-16),
04, 91, 78, 43 (Found: [M]+, 282.1075. C18H18OS requires 6.63 (1H, d, J = 8.0 Hz, H-15), 6.42 (1H, d, J = 8.0 Hz, H-7),
M]+, 282.1073). 6.35 (1H, d, J = 7.5 Hz, H-12), 6.01 (1H, d, J = 7.5 Hz, H-8),
.62 (2H, s, broad, NH2), 3.46 (1H, t, J = 12.0 Hz, H-2 endo),
3.23–3.18 (1H, m, H-1 endo), 3.12–3.01 (4H, m, H-1 exo, H-9
1
[
5
(
Sp)-(+)-[2.2]Paracyclophane-4-thiol [(Sp)-2]
To a solution of (Sp)-7 (0.51 g, 1.80 mmol, 1.0 equiv) in meth- endo, 2 × H-10), 2.71–2.62 (2H, m, H-2 exo, H-9 exo), 1.19
anol (18 mL) was added K2CO3 (3.71 g, 26.84 mmol, 15 equiv) (9H, s, t-Bu); δC (125 MHz, CDCl3) 150.6 (C), 141.6 (C), 138.5
Page 5 of 7
(page number not for citation purposes)