Lee et al.
1H NMR (500 MHz, CDCl3) δ 7.26-7.36 (m, 5 H), 5.65-5.73
(m, 2 H), 4.53 (AB, JAB ) 12.0, ∆νAB ) 14.0 Hz, 2 H), 4.22
(ddd, J ) 1.5, 4.6, 10.1 Hz, 1 H), 4.00-4.05 (m, 2 H), 3.65-
3.74 (m, 3 H), 2.82 (d, J ) 4.2 Hz, 1 H), 2.53-2.65 (m, 2 H),
2.33 (dd, J ) 6.6, 17.3 Hz, 1 H), 2.22 (dd, J ) 6.3, 17.5 Hz, 1
H), 1.77-1.93 (m, 4 H), 1.06 (dd, J ) 7.2, 7.2 Hz, 3 H); 13C
NMR (100 MHz, CDCl3) δ 138.3, 128.7, 128.4, 127.64, 127.59,
127.3, 77.9, 77.6, 73.2, 72.6, 68.1, 62.8, 33.3, 31.1, 31.0, 27.6,
12.5; IR (neat) 1540, 1211, 615 cm-1; HRMS (FAB) found
383.1220 [(M + H)+; calcd for C19H2879BrO3: 383.1220].
J ) 6.4, 15.2 Hz, 1 H), 2.46 (d, J ) 15.2 Hz, 1 H), 2.17-2.36
(m, 2 H), 1.73-1.93 (m, 2 H), 1.07 (dd, J ) 7.3, 7.3 Hz, 3 H).
(1aS,3R,3bE,5R,8R)-(5-Bromo-3-(1a-bromopropyl)-8-
(3b-iodoallyl)-2,7-dioxabicyclo[4.2.1]nonane (17). Anhy-
drous CrCl2 (181.9 mg, flame-dried under argon, 1.480 mmol)
and freshly distilled THF (12 mL, 0.01M) were stirred for 30
min at room temperature, generating a creamy gray-green
suspension. After cooling the mixture to 0 °C, a solution of
iodoform (291.5 mg, 0.740 mmol) in dry THF (1 mL) and the
crude aldehyde 16 (55.0 mg, 0.148 mmol) in dry THF (2 mL)
was injected via a syringe. The resulting dark red reaction
mixture was stirred at 0 °C to room temperature for 1 h. The
reaction mixture was quenched with H2O and diluted with
diethyl ether (10 mL). The layers were separated, and the
aqueous layer was extracted twice with diethyl ether (10 mL).
The combined organic layers were washed with saturated
aqueous Na2S2O3 and brine, dried over anhydrous Na2SO4, and
concentrated in vacuo. The residue was purified by column
chromatography (silica gel; n-hexane/ethyl acetate, 50/1) to
afford (E)-vinyl iodide 17 (49.0 mg, 67%) and (Z)-vinyl iodide
(1aS,3R,5R,8R)-8-(2-Benzyloxyethyl)-5-bromo-3-(1a-bro-
mopropyl)-2,7-dioxabicyclo[4.2.1]nonane (14). To a stirred
solution of alcohol 13 (151.0 mg, 0.394 mmol) in acetonitrile
(8 mL, 0.05M) was added N-bromosuccinimide (350.6 mg, 1.970
mmol) at room temperature. After being stirred for 30 min at
the same temperature, the reaction mixture was quenched
with saturated aqueous Na2S2O3 and diluted with diethyl ether
(10 mL). The layers were separated, and the aqueous layer
was extracted twice with diethyl ether (10 mL). The combined
organic layers were washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. The residue was purified
by column chromatography (silica gel; n-hexane/ethyl acetate,
17′ (9.8 mg, 13%). For (E)-vinyl iodide 17; [R]25 ) -49.93 (c
D
0.90, CHCl3); 1H NMR (400 MHz, CDCl3) δ 6.55 (ddd, J ) 7.4,
7.4, 14.6 Hz, 1 H), 6.24 (d, J ) 14.4 Hz, 1 H), 4.63 (d, J ) 8.5
Hz, 1 H), 4.30 (dd, J ) 2.5, 3.9 Hz, 1 H), 4.23 (dd, J ) 3.8, 9.3
Hz, 1 H), 4.14 (dd, J ) 6.4, 10.9 Hz, 1 H), 3.80-3.85 (m, 2 H),
2.47-2.54 (m, 3 H), 2.42 (d, J ) 14.3 Hz, 1 H), 2.29 (ddd, J )
9.5, 11.0, 15.0 Hz, 1 H), 2.18 (ddd, J ) 4.3, 9.3, 13.6 Hz, 1 H),
1.89 (ddddd, J ) 3.6, 7.2, 7.2, 7.2, 14.5 Hz, 1 H), 1.79 (ddddd,
J ) 7.3, 7.3, 7.3, 10.1, 14.6 Hz, 1 H), 1.06 (dd, J ) 7.3, 7.3 Hz,
3 H); 13C NMR (100 MHz, CDCl3) δ 141.5, 82.6, 81.9, 78.1,
76.3, 75.3, 62.1, 50.0, 40.8, 34.7, 33.3, 26.9, 12.9; IR (neat) 3739,
1648, 1538, 943 cm-1; HRMS (FAB) found 492.8880 [(M + H)+;
calcd for C13H2079Br2IO2: 492.8875]. For (Z)-vinyl iodide 17′:
1H NMR (400 MHz, CDCl3) δ 6.39 (d, J ) 7.5 Hz, 1 H), 6.30
(dd, J ) 7.3, 14.0 Hz, 1 H), 4.64 (d, J ) 8.5 Hz, 1 H), 4.30-
4.33 (m, 2 H), 4.17 (dd, J ) 6.0, 10.9 Hz, 1 H), 3.89-3.95 (m,
2 H), 2.68 (ddd, J ) 7.3, 7.4, 14.5 Hz, 1 H), 2.46-2.56 (m, 2
H), 2.44 (d, J ) 14.3 Hz, 1 H), 2.31 (ddd, J ) 9.5, 11.0, 13.7
Hz, 1 H), 2.20 (ddd, J ) 4.3, 8.6, 13.5 Hz, 1 H), 1.94 (ddddd, J
) 3.8, 7.2, 7.2, 7.2, 14.4 Hz, 1 H), 1.80 (ddddd, J ) 7.3, 7.3,
7.3, 10.1, 14.4 Hz, 1 H), 1.08 (dd, J ) 7.2, 7.2 Hz, 3 H); 13C
NMR (100 MHz, CDCl3) δ 137.0, 85.1, 82.3, 81.9, 76.2, 75.7,
62.1, 50.2, 40.5, 34.1, 33.4, 27.5, 12.9.
20/1) to afford 14 as a colorless oil (167.5 mg, 92%): [R]25
)
D
1
-43.23 (c 1.10, CHCl3); H NMR (500 MHz, CDCl3) δ 7.27-
7.36 (m, 5 H), 4.61 (d, J ) 8.6 Hz, 1 H), 4.52 (s, 2 H), 4.29 (dd,
J ) 2.6, 3.8 Hz, 1 H), 4.19 (dd, J ) 4.0. 9.3 Hz, 1 H), 4.15 (dd,
J ) 6.2, 10.9 Hz, 1 H), 3.97 (ddd, J ) 2.3, 6.9, 6.9 Hz, 1 H),
3.84 (ddd, J ) 3.7, 3.7, 10.2 Hz, 1 H), 3.61 (dd, J ) 6.3, 6.3
Hz, 2 H), 2.53 (dd, J ) 6.2, 15.0 Hz, 1 H), 2.41 (d, J ) 14.2 Hz,
1 H), 2.28 (ddd, J ) 9.5, 11.0, 15.0 Hz, 1 H), 2.19 (ddd, J )
4.4, 8.8, 13.6 Hz, 1 H), 2.01-2.10 (m, 2 H), 1.89 (ddddd, J )
3.7, 7.3, 7.3, 7.3, 14.6 Hz, 1 H), 1.76 (ddddd, J ) 7.3, 7.3, 7.3,
10.2, 14.6 Hz, 1 H), 1.05 (dd, J ) 7.3, 7.3 Hz, 3 H); 13C NMR
(125 MHz, CDCl3) δ 138.2, 128.4, 127.65, 127.63, 81.5, 75.97,
75.92, 73.0, 67.5, 62.2, 50.5, 40.6, 33.5, 28.5, 27.3, 12.8; IR
(neat) 1085, 796, 697, 617 cm-1; HRMS (FAB) found 461.0324
[(M + H)+; calcd for C19H2779Br2O3: 461.0327].
(1bS,3aR,5aR,8aR)-2-[5a-Bromo-3a-(1b-bromopropyl)-
2,7-dioxabicyclo[4.2.1]non-8a-yl]ethanol (15). To a stirred
solution of benzyl ether 14 (120.0 mg, 0.260 mmol) in ethanol
(5 mL, 0.05 M) was added 10% Pd/C (24.0 mg, 20 wt % of
starting material). The solution was stirred under H2 balloon
condition for 2 h at room temperature. The reaction mixture
was filtered through a pad of Celite and concentrated in vacuo.
The residue was purified by column chromatography (silica
gel; n-hexane/ethyl acetate, 4/1 to 1/1) to afford alcohol 15 as
a colorless oil (96.7 mg, 100%): [R]25D ) -46.13 (c 0.85, CHCl3);
1H NMR (500 MHz, CDCl3) δ 4.65 (d, J ) 8.6 Hz, 1 H), 4.35
(dd, J ) 2.7, 3.8 Hz, 1 H), 4.25 (dd, J ) 3.8, 9.3 Hz, 1 H), 4.14
(dd, J ) 6.1, 10.9 Hz, 1 H), 3.99 (ddd, J ) 2.3, 5.6, 8.2 Hz, 1
H), 3.79-3.87 (m, 3 H), 2.52 (dd, J ) 5.8, 15.0 Hz, 1 H), 2.43
(d, J ) 14.3 Hz, 1 H), 2.30 (ddd, J ) 9.6, 10.9, 15.0 Hz, 1 H),
2.20 (ddd, J ) 4.4, 8.8, 13.7 Hz, 1 H), 1.97-2.06 (m, 2 H), 1.90
(ddddd, J ) 3.6, 7.3, 7.3, 7.3, 14.6 Hz, 1 H), 1.79 (ddddd, J )
7.3, 7.3, 7.3, 10.1, 14.6 Hz, 1 H), 1.06 (dd, J ) 7.3, 7.3 Hz, 3
H); 13C NMR (75 MHz, CDCl3) δ 83.2, 81.8, 76.3, 76.0, 62.1,
61.0, 50.2, 40.6, 33.3, 30.9, 27.1, 12.8; IR (neat) 3398, 1289,
1137, 862, 616 cm-1; HRMS (FAB) found 370.9849 [(M + H)+;
calcd for C12H2179Br2O3: 370.9857].
(1bS,3E,3aR,5aR,8aR)-{5-[5a-Bromo-3a-(1b-bromopro-
pyl)-2,7-dioxabicyclo[4.2.1]non-8a-yl]pent-3-en-1-ynyl}-
trimethylsilane (18). To a solution of vinyl iodide 17 (32.5
mg, 0.065 mmol) in Et2NH (1 mL) was added Pd(PPh3)4 (7.5
mg, 0.006 mmol). The mixture was stirred at room tempera-
ture for 10 min in the dark (flask wrapped with foil). To a
solution of CuI (2.5 mg, 0.013 mmol) in Et2NH (1 mL) was
added trimethylsilylacetylene (12.8 mg, 0.131 mmol). The
mixture was stirred at room temperature for 10 min and then
added via syringe to the solution of vinyl iodide 17. The
reaction mixture was stirred for 1 h and concentrated in vacuo.
The residue was purified by column chromatography (silica
gel; n-hexane/ethyl acetate, 50/1) to afford (E)-enyne 18 (22.7
mg, 75%): [R]25D ) -55.80 (c 0.61, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 6.20 (ddd, J ) 7.4, 7.4, 15.7 Hz, 1 H), 5.67 (d, J )
15.9 Hz, 1 H), 4.62 (d, J ) 8.6 Hz, 1 H), 4.30 (dd, J ) 2.4, 3.8
Hz, 1 H), 4.23 (dd, J ) 4.0, 9.3 Hz, 1 H), 4.14 (dd, J ) 6.2,
10.8 Hz, 1 H), 3.79-3.85 (m, 2 H), 2.50-2.57 (m, 3 H), 2.42
(d, J ) 14.3 Hz, 1 H), 2.28 (ddd, J ) 9.5, 10.9, 15.0 Hz, 1 H),
2.16 (ddd, J ) 4.4, 9.5, 13.5 Hz, 1 H), 1.90 (ddddd, J ) 3.7,
7.3, 7.3, 7.3, 14.6 Hz, 1 H), 1.78 (ddddd, J ) 7.3, 7.3, 7.3, 10.1,
(1aS,3R,5R,8R)-[5R-Bromo-3R-(1aS-bromopropyl)-2,7-
dioxabicyclo[4.2.1]non-8R-yl]acetaldehyde (16). To a so-
lution of alcohol 15 (95.4 mg, 0.256 mmol) in dry CH2Cl2 (5
mL, 0.05M) was added Dess-Martin periodinane (271.9 mg,
0.641 mmol) at room temperature. The reaction mixture was
stirred for 3 h, diluted with n-hexane (10 mL), filtered through
a short plug of silica gel, and concentrated in vacuo to give
the crude aldehyde 16 (80.5 mg, 85%). Without further
purification, the crude aldehyde 16 was carried on to the next
14.6 Hz, 1 H), 1.06 (dd, J ) 7.2, 7.2 Hz, 3 H), 0.17 (s, 9 H); 13
C
NMR (125 MHz, CDCl3) δ 140.5, 112.9, 103.4, 94.0, 83.2, 81.9,
76.3, 75.2, 62.0, 50.2, 40.2, 33.4, 31.8, 27.1, 12.9, -0.1; IR (neat)
2131, 1729, 1249, 1135 cm-1; HRMS (FAB) found 463.0305 [(M
+ H)+; calcd for C18H2979Br2O2Si: 463.0304].
1
step. H NMR (300 MHz, CDCl3) δ 9.83 (s, 1 H), 4.65 (d, J )
3-(E)-Isoprelaurefucin (4). To a cooled (0 °C) solution of
enyne 18 (18.0 mg, 0.039 mmol) in THF (2 mL, 0.02 M) was
added dropwise TBAF (0.10 mL, 1.0 M solution in THF, 0.100
8.6 Hz, 1 H), 4.33-4.41 (m, 2 H), 4.10-4.20 (m, 2 H), 3.84
(ddd, J ) 3.7, 3.7, 10.3 Hz, 1 H), 2.89-2.98 (m, 2 H), 2.52 (dd,
8728 J. Org. Chem., Vol. 70, No. 22, 2005