A. Friberg et al. / Tetrahedron: Asymmetry 19 (2008) 1765–1777
1773
(s, 3H), 2.50 (dd, J = 14.8, 2.6 Hz, 1H), 2.37 (doublet of multiplets,
J = 14.7 Hz, 1H), 2.27 (s, 1H), 2.09–2.03 (m, 1H), 1.98 (d, J = 15.0,
1H), 1.77 (ddd, J = 14.3, 8.8, 1.8 Hz, 1H), 1.35–1.26 (m, 1H), 1.26–
1.17 (m, 1H), 1.16–1.05 (m, 2H); 13C NMR (100 MHz, C6D6) d
158.3, 134.3, 128.6, 127.4, 121.2, 112.2, 76.3, 68.5, 55.0, 35.6,
34.3, 34.1, 33.4, 22.9, 22.1; HRMS (FAB+, direct inlet) [M] calcd
for C15H20O3: 248.1412; found 248.1411. C15H20O3 requires C,
72.55; H, 8.12. Found: C, 72.47; H, 8.06.
55.1 mmol) following procedure C. The residue was purified by col-
umn chromatography (SiO2, heptane–EtOAc 90:10) to give 10a
(492 mg, 23%) as a white solid: TLC Rf = 0.69 (SiO2, heptane–EtOAc
50:50); mp 187–189 °C (from toluene); [a]D = +74 (c 0.50, CHCl3).
1H NMR data were consistent with those reported for ( )-10a
(see below).
4.1.23. (1S,2R,4S,5R)-2,5-Di(naphthalen-1-yl)bicyclo[2.2.2]oct-
7-ene-2,5-diol 10b
4.1.19. (1S,2S,4S,5S)-2,5-Diphenylbicyclo[2.2.2]octane-2,5-diol
7a
The title compound was synthesized from (À)-13 (900 mg,
6.61 mmol) of >98% ee, 1-naphthylMgBr (3 Â 2.5 equiv, 1 M in
THF, 49.6 mmol) and water (3 Â 2.5 equiv, 49.6 mmol) following
procedure C. The residue was purified by column chromatography
(SiO2, heptane–EtOAc 90:10) to give 10b (318 mg, 12%) as a white
solid: TLC Rf = 0.82 (SiO2, pentane:ether 40:60); mp 148–151 °C
The title compound was synthesized from 9a (175 mg,
0.81 mmol), PhMgBr (3 Â 2.5 equiv, 1.0 M in THF, 6.08 mmol) and
water (3 Â 2.5 equiv, 6.08 mmol) following procedure C. The resi-
due was purified by column chromatography (SiO2, heptane–EtOAc
90:10, then 50:50 when 7a started to elute) to give 7a (170 mg,
71%) as a white solid: TLC Rf = 0.63 (SiO2, heptane–EtOAc 50:50);
(melt and decomposition); [
a]D = +13.7 (c 1.53, CHCl3); IR (KBr)
3227 cmÀ1 1H NMR (400 MHz, CDCl3) d 8.82 (d, J = 8.7 Hz, 2H),
;
mp 147–149 °C; [
a
]
D = À87 (c 0.40, tBuOMe); IR (KBr) 3387,
7.88 (dd, J = 8.0, 1.4 Hz, 2H), 7.78 (d, J = 8.1 Hz, 2H), 7.60–7.54 (m,
2H), 7.54–7.46 (m, 4H), 7.38 (t, J = 8.0 Hz, 2H), 6.40 (dd, J = 4.4,
3.2 Hz, 2H), 3.44–3.38 (m, 2H), 3.34 (dd, J = 14.1, 3.1 Hz, 2H), 3.04
(s, 2H), 2.01 (dd, J = 14.0, 2.7 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 143.8, 135.6, 132.7, 131.7, 129.4, 129.1, 127.9, 125.9, 125.9,
124.9, 123.2, 78.3, 43.7, 40.7; HRMS (FAB+, direct inlet) [M] calcd
for C28H24O2Na: 415.1674; found 415.1668. C20H24O4 requires C,
85.68; H, 6.16. Found: C, 85.40; H, 6.08.
3277 cmÀ1 1H NMR (300 MHz, CDCl3) d 7.61 (d, J = 7.4 Hz, 4H),
;
7.41 (t, J = 7.2 Hz, 4H), 7.31 (t, J = 7.3 Hz), 2H), 3.53 (s, 2H), 2.58
(dd, J = 14.8, 4.1 Hz), 2H), 2.41 (br s, 2H), 2.32 (dd, J = 14.7,
1.6 Hz, 2H), 1.44 (br s, 4H); 13C NMR (75 MHz, CDCl3) d 146.3,
128.5, 127.4, 126.2, 74.5, 37.8, 37.4, 21.5; HRMS (FAB+, direct inlet)
[M] calcd for C20H22O2: 294.1620; found 294.1619. C20H22O2 re-
quires C, 81.60; H, 7.53. Found: C, 81.48; H, 7.49.
4.1.20. (1S,2S,4S,5S)-2,5-Di(naphthalen-1-yl)bicyclo[2.2.2]-
octane-2,5-diol 7b
4.1.24. (1S,2R,4S,5R)-2,5-Bis(2-methoxyphenyl)bicyclo-
[2.2.2]oct-7-ene-2,5-diol 10c
The title compound was synthesized from 9b (350 mg,
1.31 mmol), 1-naphthylMgBr (3 Â 2.5 equiv, 1 M in THF, 9.83
mmol) and water (3 Â 2.5 equiv, 9.83 mmol) following procedure
C. The residue was purified by column chromatography (SiO2, hep-
tane–EtOAc 85:15) to give 7b (487 mg, 94%) as a white solid: TLC
Rf = 0.66 (SiO2, heptane–EtOAc 50:50); mp 147–151 °C;
The title compound was synthesized from (À)-13 (400 mg,
2.94 mmol) of >98% ee (HPLC, Chiralcel OD-H) and o-Anisyllithium
(4 equiv, 11.8 mmol) following procedure B. The residue was puri-
fied by column chromatography (SiO2, heptane–EtOAc 85:15 to
33:67) to give 10c (128 mg, 12%) as a white solid: TLC Rf = 0.38
(SiO2, heptane–EtOAc 50:50); mp 89–93 °C (melt and decomp.);
[
a]
D = À110 (c 0.45, tBuOMe); IR (KBr) 3254 cmÀ1
;
1H NMR
[a
]
D = À147 (c 0.23, CH2Cl2); IR (KBr) 3380 cmÀ1
;
1H NMR
(400 MHz, C6D6) d 9.07 (d, J = 8.7 Hz, 2H), 7.73 (d, J = 8.1 Hz, 2H),
7.64 (d, J = 7.8 Hz, 2H), 7.51–7.44 (m, 2H), 7.39–7.32 (m, 2H),
7.26 (d, J = 6.2 Hz, 2H), 7.22 (t, J = 7.5 Hz, 2H), 3.86 (br s, 2H),
2.81 (d, J = 13.7 Hz, 2H), 2.41 (br s, 2H), 1.95 (d, J = 14.8 Hz, 2H),
1.43–1.30 (m, 2H), 1.16–1.01 (m, 2H); 13C NMR (100 MHz, C6D6)
d 141.70, 136.4, 133.2, 129.6, 129.4, 129.2, 125.9, 125.8, 124.7,
124.2, 76.32, 39.6, 37.1, 22.8; HRMS (ES+) [M] calcd for
(300 MHz, CDCl3) d 7.25–7.17 (m, 4H), 6.95–6.87 (m, 4H), 6.17
(dd, J = 4.5, 3.1 Hz, 2H), 4.20 (s, 2H), 3.93 (s, 6H), 3.22–3.15 (m,
2H), 2.92 (dd, J = 14.2, 2.6 Hz, 2H), 1.97 (dd, J = 14.2, 3.2 Hz, 2H);
13C NMR (75 MHz, CDCl3) d 157.5, 136.7, 133.0, 128, 1, 126.9,
120.5, 111.5, 76.7, 55.8, 41.5, 38.3; HRMS (FAB+, direct inlet) [M]
calcd for C20H24O4: 352.1675; found 352.1671. C20H24O4 requires
C, 74.98; H, 6.86. Found: C, 74.84; H, 6.73.
C28H26O2Na: 417.1831; found 417.1844. C28H26O2 requires C,
85.25; H, 6.64. Found: C, 85.15; H, 6.61.
4.1.25. (1R,2S,4R,5S)-2-(Naphthalen-1-yl)bicyclo[2.2.2]oct-7-
ene-2,5-diol 12
4.1.21. (1S,2S,4S,5S)-2,5-Bis(2-methoxyphenyl)bicyclo-
[2.2.2]octane-2,5-diol 7c
The title compound was synthesized from 9c (970 mg,
3.94 mmol) and o-anisyllithium (4 equiv, 15.8 mmol) following
procedure B. The residue was purified by column chromatography
(SiO2, heptane–EtOAc 67:33, TLC Rf = 0.37) to give 7c (873 mg, 63%)
The title compound was synthesized from 11 (200 mg, 1.45
mmol) of >99% ee, 1-naphthylMgBr (3 Â 2.5 equiv, 1 M in THF,
10.9 mmol) and water (3 Â 2.5 equiv, 10.9 mmol) following proce-
dure C. The residue was purified by column chromatography (SiO2,
heptane–EtOAc 75:25) to give 12 (54 mg, 14%) as a white solid: TLC
Rf = 0.32 (SiO2, heptane–EtOAc 50:50); mp 75–78 °C; [
a
]
D = À44 (c
as a white solid: mp 162–167 °C; [
a]
D = À24 (c 0.32, CH2Cl2); IR
0.45, tBuOMe); IR (KBr) 3381 cmÀ1 1H NMR (400 MHz, C6D6) d
;
(KBr) 3549 cmÀ1 1H NMR (300 MHz, C6D6) d 7.40 (d, J = 7.7 Hz,
;
8.84 (d, J = 8.8 Hz, 1H), 7.68 (doublet of multiplets, J = 8.1 Hz, 1H),
7.57 (dd, J = 6.3, 2.9 Hz, 1H), 7.41–7.34 (m, 1H), 7.33–7.28 (m,
1H), 7.20–7.16 (m, 2H), 6.20–6.14 (m, 1H), 5.81–5.75 (m, 1H),
3.79 (d, J = 9.7 Hz, 1H), 2.92 (dd, J = 13.9, 2.7 Hz, 1H), 2.81–2.76
(m, 1H), 2.45–2.39 (m, 1H), 2.06 (dt, J = 13.7, 2.4 Hz, 1H), 1.86–
1.58 (m, 4H); 13C NMR (100 MHz, C6D6) d 145.0, 136.0, 135.3,
132.4, 131.8, 129.5, 128.9, 128.4, 125.94, 125.9, 124.9, 123.4,
78.5, 68.2, 42.7, 39.7, 38.0, 32.8; HRMS (FAB+, direct inlet) [M]
calcd for C18H18O2Na: 289.1204; found 289.1220.
2H), 7.10 (t, J = 8.1 Hz, 2H), 6.88 (t, J = 7.5 Hz, 2H), 6.57 (d,
J = 8.2 Hz, 2H), 4.86 (s, 2H), 3.21 (s, 6H), 3.23–3.17 (m, 2H), 2.62
(br s, 2H), 2.34 (dd, J = 15.0, 2.3 Hz, 2H), 1.39–1.24 (m, 4H); 13C
NMR (75 MHz, C6D6) d 159.1, 135.2, 128.6, 127.6, 120.9, 112.7,
75.5, 55.3, 37.3, 36.9, 22.2; HRMS (FAB+, direct inlet) [M] calcd
for C22H26O4: 354.1831; found 354.1836. C22H26O4 requires C,
74.55; H, 7.39. Found: C, 74.63; H, 7.43.
4.1.22. (1R,2S,4R,5S)-2,5-Diphenylbicyclo[2.2.2]oct-7-ene-2,5-
diol 10a
The title compound was synthesized from (+)-13 (1.00 g,
7.35 mmol) of >98% ee (HPLC, Chiralcel OD-H), PhMgBr (3 Â
2.5 equiv, 1.0 M in THF, 55.1 mmol) and water (3 Â 2.5 equiv,
4.1.26. Typical procedure D. (1S,4S,5S)-5-Hydroxy-5-phenyl-
bicyclo[2.2.2]octan-2-one 9a
N-Methylmorpholine N-oxide (281 mg, 2.40 mmol), 3 Å
crushed molecular sieves (827 mg) and tetrapropylammoniumper-