Vol. 64, No. 9 (2016)
Chem. Pharm. Bull.
1375
289mmol) in CH2Cl2 (90mL) at −78°C. After stirring for chromatography (4:1 hexanes/EtOAc) to afford 27 (563mg,
0.5h at −78°C, the reaction mixture was quenched with a 96%) as an amorphous yellow solid: [α]D25 +66.1 (c=1.0,
saturated aq Na2CO3 solution. The aqueous layer was extract- CHCl3); IR (neat) cm−1: 3020, 1773, 1639, 1215; 1H-NMR
ed with CH2Cl2. The combined organic extracts were dried (400MHz, CDCl3) δ: 3.50 (d, 1H, J=10.4Hz), 3.27 (d, 1H,
over Na2SO4, filtered, and concentrated in vacuo. The residue J=10.4Hz), 2.82 (dd, 1H, J=18.0, 10.0Hz), 2.61 (dd, 1H,
was purified by flash silica gel column chromatography (4:1 J=18.8, 7.6Hz), 2.50–2.41 (m, 3H), 1.77 (dd, 1H, J=12.2,
hexanes/EtOAc) to afford 25 (8.55g, 90%) as a colorless amor- 7.6Hz), 1.64–1.01 (m, 6H), 0.91 (s, 3H), 0.88 (s, 3H), 0.77 (s,
phous solid. The spectroscopic data for 25 were identical to 3H); 13C-NMR (400MHz, CDCl3) δ: 204.3, 174.0, 86.1, 54.6,
those reported in the literature.31)
48.0, 41.3, 39.3, 36.2, 36.1, 33.1, 32.2, 30.0, 21.1, 17.8, 13.6,
2-((1R,3R,4aS,8aS)-3-Hydroxy-5,5,8a-trimethyl-2-meth- 10.3; HR-MS (ESI) [M+Na]+ Calcd for C16H23NaIO3 413.0590.
ylenedecahydronaphthalen-1-yl)-N-methoxy-N-methylacet- Found 413.0600.
amide (23) A solution of 25 (5.00g, 17.0mmol) in CH2Cl2
(2R,3aR,4S,5aS,9aS,9bR)-3a-(Iodomethyl)-6,6,9a-
(85mL) was treated with SeO2 (37.8mg, 0.341mmol), sali- trimethyldodecahydronaphtho[2,1-b]furan-2,4-diol (22)
A
cylic acid (235mg, 1.70mmol), and tert-butylhydroperoxide solution of 27 (50.6mg, 0.130mmol) in CH2Cl2 (1.3mL) was
(TBHP) (5.0M solution in decane, 10.2mL, 51.1mmol) at room treated with DIBAL (1.02M in n-hexane, 458µL, 0.467mmol)
temperature. After stirring for 24h at room temperature, the at −78°C. After stirring for 0.5h at −78°C, the reaction mix-
reaction mixture was quenched with a saturated aq Na2S2O3 ture was quenched with MeOH. The organic layer was washed
solution. The aqueous layer was extracted with CH2Cl2. The sequentially with 1M HCl and H2O, dried over Na2SO4, fil-
organic layer was combined, dried over Na2SO4, filtered, and tered, and concentrated in vacuo. The residue was purified
concentrated in vacuo. The residue was purified by flash silica by flash silica gel column chromatography (4:1 hexanes/
gel column chromatography (1:1 hexanes/EtOAc) to afford 23 EtOAc) to afford 22 (32.1mg, 63%) as a colorless amorphous
(3.22g, 61%) as an amorphous brown solid: [α]D26–69.1 (c=1.0, solid: [α]D25 –27.0 (c=1.0, CHCl3); IR (neat) cm−1: 3486, 2932,
CHCl3); IR (neat) cm−1: 3455, 3021, 1648, 1388, 1215, 1036; 1423, 1215, 1061; 1H-NMR (400MHz, CDCl3) δ: 5.50 (t,
1H-NMR (400MHz, CDCl3) δ: 4.91 (s, 1H), 4.52 (s, 1H), 4.31 1H, J=6.0Hz), 4.06 (dd, 1H, J=11.6, 6.4Hz), 3.70 (d, 1H,
(t, 1H, J=2.8Hz), 3.68 (s, 3H), 3.10 (s, 3H), 2.93 (dd, 1H, J=10.4Hz), 3.62 (d, 1H, J=10.4Hz), 2.28 (d, 1H, J=7.6Hz),
J=10.4, 3.6Hz), 2.60 (dd, 1H, J=16.0, 10.4Hz), 2.39 (dd, 1H, 2.22 (dd, 1H, J=14.2, 6.0Hz), 1.99 (ddd, 1H, J=14.2, 7.6,
J=16.0, 3.6Hz), 1.85 (dt, 1H, J=13.2, 2.8Hz), 1.75 (dd, 1H, 6.0Hz), 1.81 (ddd, 1H, J=11.6, 6.4, 0.8Hz), 1.57–0.80 (m, 8H),
J=13.2, 2.8Hz), 1.55–1.13 (m, 7H), 0.86 (s, 3H), 0.77 (s, 3H), 0.91 (s, 3H), 0.86 (s, 3H), 0.84 (s, 3H); 13C-NMR (400MHz,
0.67 (s, 3H); 13C-NMR (400MHz, CDCl3) δ: 174.4, 150.8, CDCl3) δ: 99.1, 85.9, 71.4, 56.5, 49.5, 41.4, 40.8, 35.8, 35.3,
109.1, 73.5, 61.4, 47.2, 46.2, 42.0, 39.1, 38.7, 33.3, 33.1, 32.5, 33.6, 32.8, 27.8, 22.3, 18.1, 15.7, 12.9; HR-MS (ESI) [M+Na]+
30.5, 26.9, 21.7, 19.3, 13.8; HR-MS (ESI) [M+Na]+ Calcd for Calcd for C16H27NaIO3 417.0903. Found 417.0904.
C18H31NNaO3 332.2202. Found 332.2203.
(1R,2S,3S,4aS,8aS)-1-Allyl-5,5,8a-trimethyloctahydro-
(3aR,4R,5aS,9aS,9bR)-4-Hydroxy-3a-(iodomethyl)- 1H-spiro[naphthalene-2,2′-oxiran]-3-ol (29) To a suspen-
6,6,9a-trimethyldecahydronaphtho[2,1-b]furan-2(3aH)-one sion of Ph3PMeBr (214mg, 0.600mmol) in THF (0.6mL) was
(26) To a solution of 23 (2.71g, 8.75mmol) in MeCN–H2O added dropwise n-BuLi (1.63M in THF, 367µL, 0.600mmol) at
(2:1, 88mL) was added NIS (3.94g, 17.5mmol) at room tem- −78°C. After stirring for 1h at 0°C, a solution of 22 (33.7mg,
perature. After stirring for 1h at room temperature, the reac- 0.0855mmol) in THF (0.5mL) was added. After stirring for an
tion mixture was quenched with a saturated aq Na2CO3 solu- additional 1h at 0°C, the reaction mixture was quenched with
tion and a saturated aq Na2S2O3 solution. The aqueous layer a saturated aq NH4Cl solution and extracted with EtOAc. The
was extracted with EtOAc. The combined organic extracts combined organic extracts were washed with H2O, dried over
were dried over Na2SO4, filtered, and concentrated in vacuo. Na2SO4, filtered, and concentrated in vacuo. The residue was
The residue was purified by flash silica gel column chro- purified by flash silica gel column chromatography (12:1 hex-
matography (4:1 hexanes/EtOAc) to afford 26 (3.17g, 92%) anes/EtOAc) to afford 29 (20.0mg, 89%) as a colorless amor-
as an amorphous yellow solid: [α]D26 –13.5 (c=1.0, CHCl3); phous solid: [α]D25 +36.3 (c=1.0, CHCl3); IR (neat) cm−1: 3476,
1
IR (neat) cm−1: 3488, 2851, 2067, 1771, 1418, 1214, 1060; 3078, 2958, 2928, 1521, 1398, 1215, 1082; H-NMR (400MHz,
1H-NMR (400MHz, CDCl3) δ: 4.34 (t, 1H, J=8.8Hz), 3.96 (d, CDCl3) δ: 5.70 (m, 1H), 4.97–4.92 (m, 2H), 3.66 (dt, 1H,
1H, J=11.2Hz), 3.27 (d, 1H, J=11.2Hz), 2.82 (dd, 1H, J=19.2, J=11.6, 5.2Hz), 2.87 (d, 1H, J=4.8Hz), 2.62 (d, 1H, J=4.8Hz),
11.2Hz), 2.40 (dd, 1H, J=19.2, 4.0Hz), 2.12 (dd, 1H, J=11.2, 2.05–2.00 (m, 2H), 1.92 (brd, 1H, J=11.6Hz), 1.77–1.63 (m,
4.0Hz), 1.93 (dt, 1H, J=18.4, 8.8Hz), 1.61–0.86 (m, 8H), 0.93 2H), 1.62–0.90 (m, 8H), 0.90 (s, 3H), 0.84 (s, 3H), 0.83 (s, 3H);
(s, 3H), 0.91 (s, 3H), 0.86 (s, 3H); 13C-NMR (400MHz, CDCl3) 13C-NMR (400MHz, CDCl3) δ: 140.1, 114.7, 69.3, 60.0, 52.4,
δ: 176.2, 88.9, 70.1, 54.9, 48.2, 42.6, 41.6, 37.0, 33.6, 32.3, 31.1, 50.4, 44.9, 41.9, 39.4, 39.0, 33.4, 33.3, 30.6, 25.5, 21.6, 18.5,
27.2, 21.2, 18.1, 17.0, 15.5; HR-MS (ESI) [M+Na]+ Calcd for 14.6; HR-MS (ESI) [M+Na]+ Calcd for C17H28NaO2 287.1987.
C16H25NaIO3 415.0746. Found 415.0741.
Found 287.1973.
(3aR,5aS,9aS,9bR)-3a-(Iodomethyl)-6,6,9a-trimethyl-
(1R,2S,3S,4aS,8aS)-5,5,8a-Trimethyl-1-((Z)-3-methyl-
penta-2,4-dien-1-yl)octahydro-1H-spiro[naphthalene-2,2′-
octahydronaphtho[2,1-b]furan-2,4(3aH,5H)-dione (27)
A
suspension of 26 (600mg, 1.70mmol) and 4Å molecular sieves oxiran]-3-ol (21) A solution of 29 (29.6mg, 0.112mmol)
(1.00g) in CH2Cl2 (15mL) was treated with PCC (660mg, in CH2Cl2 (2.2mL) was treated with methacrolein (173µL,
3.06mmol) at room temperature. After stirring for 1.5h 1.68mmol) and a catalytic amount of Grubbs second-genera-
at room temperature, the resulting suspension was filtered tion catalyst (9.5mg, 0.0112mmol) at room temperature. After
through a pad of Celite, and the filtrate was concentrated in stirring for 4.5h at reflux, the reaction mixture was cooled
vacuo. The residue was purified by flash silica gel column to room temperature and concentrated in vacuo. The residue