P. M. Pihko et al.
(53 mg, 0.049 mmol, 100 mol-%) in CH2Cl2 (3.5 mL) was added H, 4-Hb), 0.43 (s, 3 H, 11-OSi-Mea), 0.36 (s, 3 H, 11-OSi-Meb),
FULL PAPER
chloroacetic acid (2.3 mg, 0.024 mol-%, 50 mol-%) at room temp.
The reaction mixture was stirred at room temp. for 1 h and then
diluted with CH2Cl2 (5 mL) and quenched with satd. aq. NaHCO3
(5 mL). The separated organic layer was dried with Na2SO4 and
concentrated. Purification of the residue by flash chromatography
(10% EtOAc/hexanes, 50 μL Et3N in 250 mL eluent) afforded the
nonanomeric isomer 30 as a colorless oil (15 mg, 29%) and a mix-
ture of the nonanomeric and anomeric isomer 29 (35 mg, combined
0.14 (s, 6 H, 14-OSi-Me2) ppm. 13C NMR (100 MHz, CD3CN): δ
= 139.5, 136.42, 136.37, 136.36, 134.8, 130.7, 130.6, 129.2, 128.74,
128.66, 128.62, 128.4, 107.0, 105.8, 85.7, 84.7, 84.6, 83.0, 81.5, 74.0,
73.4, 72.9, 72.7, 67.5, 66.6, 49.7, 42.1, 41.4, 40.4, 34.8, 34.7, 32.5,
28.5, 28.0, 27.3, 26.52, 26.47, 26.41, 21.1, 21.0, 19.8, 19.2, 18.6,
15.1, –2.7, –3.9, –4.4, –4.7 ppm. HRMS (ESI+): calcd. for
C60H94O9NaSi3 1065.6103; found 1065.6104 (Δ = 0.1 ppm).
(2S,3R,6S,8S)-2-((2R,4R,5S)-5-((1S,3R,5S)-1-[(Benzyloxy)meth-
yl]-5-methyl-2,8-dioxabicyclo[3.2.1]octan-3-yl)-4-hydroxy-2-meth-
yltetrahydrofuran-2-yl)-8-[(S)-1-hydroxypropan-2-yl]-1,7-dioxa-
spiro[5.5]undecan-3-ol (31a): To a solution of spiroketal 29 (6.0 mg,
0.006 mmol, 100 mol-%) in THF (0.5 mL), was added TBAF (1 m
in THF, 56 μL, 0.06 mmol, 1000 mol-%) at room temp. The reac-
tion mixture was stirred at room temp. for 24 h and then diluted
with Et2O (4 mL). The orange oil that separated from the solution
was separated from the solution, and the solvent was evaporated.
The crude product was dissolved in CH2Cl2 (1 mL) and pTsOH
(0.5 mg, 0.003 mmol, 50 mol-%) was added. The reaction mixture
was stirred at room temp. for 19 h then diluted with CH2Cl2 (4 mL)
and satd. aq. NaHCO3 (2 mL) was added. The layers were sepa-
rated and the organic layer was dried with Na2SO4 and concen-
trated. Purification of the residue by flash chromatography (90%
EtOAc/hexanes) afforded the [6,6]-spiroketal product 31 as a color-
less oil (2.8 mg, 86%). Rf = 0.26 (90% EtOAc/hexanes). [α]D = 1.7
total yield 98%). For 30: Rf = 0.38 (15% EtOAc/hexanes). [α]D
=
–13.2 (c = 0.50, CH Cl ). IR (film): ν = 2953, 2929, 2856, 1472,
˜
2
2
1106 cm–1. 1H NMR (400 MHz, C6D6): δ = 7.82–7.78 (m, 4 H,
TBDPS), 7.36–7.19 (m, 10 H, TBDPS, Bn), 7.11–7.07 (m, 1 H,
TBDPS), 4.54 (ddAB, |JAB| = 12.3 Hz, Δv = 23.9 Hz, 2 H, Bn), 4.40–
4.34 (m, 2 H, 16-H, 10-H), 4.22 (dd, J = 4.7, 2.8 Hz, 1 H, 14-H),
3.88 (d, J = 8.2 Hz, 1 H, 11-H), 3.85 (dd, J = 9.7, 7.3 Hz, 1 H, 1-
H), 3.80 (s, 2 H, 22-H), 3.62 (dd, J = 11.1, 2.9 Hz, 1 H, 15-H), 3.60
(dd, J = 9.7, 6.0 Hz, 1 H, 1-H), 3.58–3.56 (m, 1 H, 3-H), 2.41 (dt,
J = 13.2, 4.5 Hz, 1 H, 20-Ha), 2.32 (d, J = 13.9 Hz, 1 H, 13-Ha),
2.23–1.96 (m, 5 H, 6-Ha, 8-Ha, 9-H, 20-Hb), 1.86 (app t, J =
10.5 Hz, 1 H, 17-Hax), 1.82–1.49 (m, 11 H, 2-H, 4-H, 5-H, 6-Hb,
8-Hb, 13-Hb, 17-Heq, 19-H), 1.29 (s, 3 H, 43-H), 1.24 (s, 3 H, 42-
H), 1.19 (s, 9 H, TBDPS), 1.10 (s, 9 H, 14-OSi-tBu), 1.04 (s, 9 H,
11-OSi-tBu), 1.00 (d, J = 6.8 Hz, 3 H, 41-H), 0.48 (s, 3 H, 14-OSi-
Mea), 0.37 (s, 3 H, 14-OSi-Meb), 0.13 (s, 3 H, 11-OSi-Mea), 0.12 (s,
3 H, 11-OSi-Meb) ppm. 13C NMR (100 MHz, CD3CN): δ = 139.6,
136.4, 136.3, 134.80, 134.76, 130.6, 130.7, 129.2, 128.8, 128.75,
128.72, 128.4, 108.0, 107.0, 85.9, 84.6, 81.8, 81.4, 80.2, 74.0, 73.5,
72.94, 72.88, 67.2, 66.6, 49.2, 41.6, 41.3, 35.6, 34.7, 33.7, 32.5, 29.3,
28.9, 27.2, 26.7, 26.41, 26.37, 23.0, 21.8, 19.8, 19.3, 18.6, 11.6, –2.7,
–4.1, –4.2, –4.9 ppm. HRMS (ESI+): calcd. for C60H94O9NaSi3
1065.6103; found 1065.6095 (Δ = 0.8 ppm).
(c = 0.23, CH Cl ). IR (film): ν = 3401, 2918, 2850, 1454,
˜
2
2
1
1099 cm–1. H NMR (400 MHz, CD3CN): δ = 7.36–7.28 (m, 5 H,
Bn), 4.56 (s, 2 H, Bn), 4.19 (d, J = 10.7 Hz, 1 H, 14-OH), 4.19–
4.14 (m, 1 H, 16-H), 4.03–3.99 (m, 1 H, 14-H), 3.81–3.78 (m, 1 H,
10-H), 3.74 (ddd, J = 11.6, 5.1, 2.2 Hz, 1 H, 3-H), 3.56–3.53 (m, 1
H, 1-Ha), 3.51 (d, J = 1.1 Hz, 1 H, 11-H), 3.47 (s, 2 H, 22-H), 3.42
(dd, J = 7.9, 2.4 Hz, 1 H, 15-H), 3.39–3.33 (m, 1 H, 1-Hb), 2.77 (d,
J = 6.4 Hz, 1 H, 10-OH), 2.66 (dd, J = 6.5, 4.9 Hz, 1 H, 1-OH),
2.49 (d, J = 14.5 Hz, 1 H, 13-Ha), 2.12–2.07 (m, 2 H, 8-Ha, 20-Ha),
2.01–1.96 (m, 2 H, 4-Heq, 9-Ha), 1.87–1.75 (m, 4 H, 5-Ha, 13-Hb,
19-Ha, 20-Hb), 1.70–1.51 (m, 8 H, 2-H, 5-Hb, 6-Ha, 8-Hb, 9-Hb, 17-
H, 19-Hb), 1.47 (dd, J = 13.9, 5.1 Hz, 1 H, 6-Hb), 1.38 (ddd, J =
14.0, 4.5, 2.3 Hz, 1 H, 4-Hax), 1.29 (s, 3 H, 43-H), 1.20 (s, 3 H, 42-
H), 0.91 (d, J = 6.9 Hz, 3 H, 41-H) ppm. HRMS (ESI+): calcd. for
C32H48O9Na 599.3196; found 599.3219 (Δ = 3.8 ppm).
Equilibration Experiment
((S)-((2R,4R,5R)-5-((1S,3R,5S)-1-[(Benzyloxy)methyl]-5-methyl-
2,8-dioxabicyclo[3.2.1]octan-3-yl)-4-[(tert-butyldimethylsilyl)oxy]-
2-methyltetrahydrofuran-2-yl)((2R,5R,7S)-7-((S)-1-[(tert-butyldi-
phenylsilyl)oxy]propan-2-yl)-1,6-dioxaspiro[4.5]decan-2-yl)meth-
oxy)(tert-butyl)dimethylsilane (29): To a solution of a 1:1 mixture of
spiroketals 29 and 30 (40 mg, 0.038 mmol, 100 mol-%) in CH2Cl2
(2.0 mL), was added PPTS (1.9 mg, 0.0075 mmol, 20 mol-%) at
room temp. After 4 h, a second portion of PPTS (9.5 mg,
0.038 mmol, 100 mol-%) was added. Stirring was continued at
room temp. for 2 h, then the reaction mixture was diluted with
CH2Cl2 (5 mL) and quenched by addition of satd. aq. NaHCO3
(4 mL). The layers were separated and the organic layer was dried
with Na2SO4 and concentrated. Purification of the residue by flash
chromatography (10% EtOAc/hexanes, 25 μL Et3N in 125 mL elu-
ent) afforded the anomeric isomer 29 as a colorless oil (26.5 mg,
(2S,3R,5R)-Methyl 3-[(tert-Butyldimethylsilyl)oxy]-5-{(S)-2-[(tert-
butyldimethylsilyl)oxy]-1-hydroxyethyl}-5-methyltetrahydrofuran-
2-carboxylate (33): To a solution of (2S,3R,5R)-methyl 5-{(S)-2-
[(tert-butyldimethylsilyl)oxy]-1-hydroxyethyl}-3-hydroxy-5-meth-
yltetrahydrofuran-2-carboxylate (0.10 g, 0.3 mmol, 100 mol-%) in
CH2Cl2 (2 mL) at –78 °C, was added dropwise over a period of
30 min, a solution of 2,6-lutidine (70 μL, 0.6 mmol, 200 mol-%)
and TBSOTf (76 μL, 0.33 mmol, 110 mol-%) in CH2Cl2 (2 mL).
67%). For 29: Rf = 0.34 (15% EtOAc/hexanes). [α]D = 0.6 (c = The reaction was stirred at –78 °C for 25 min and then quenched
0.50, CH Cl ). IR (film): ν = 2953, 2929, 2856, 1472, 1110 cm–1. by addition of MeOH (1 mL). The solution was warmed to room
˜
2
2
1H NMR (400 MHz, C6D6): δ = 7.85–7.79 (m, 4 H, Si-Ph), 7.36– temp. then washed with H2O (2 mL) and brine (2 mL), dried with
7.18 (m, 10 H, Si-Ph, Bn), 7.10–7.06 (m, 1 H, Si-Ph), 4.54 (ddAB
,
Na2SO4, and concentrated. Purification of the residue by flash
chromatography (10% EtOAc/hexanes) afforded the desired prod-
uct 34 as a colorless viscous oil (0.12 g, 92%). Rf = 0.73 (50%
|JAB| = 12.3 Hz, Δv = 26.4 Hz, 2 H, Bn), 4.35 (ddd, J = 11.5, 8.0,
3.7 Hz, 1 H, 16-H), 4.20 (dd, J = 5.0, 3.2 Hz, 1 H, 14-H), 3.96–
3.86 (m, 3 H, 1-Ha, 3-H, 10-H), 3.81 (d, J = 7.8 Hz, 1 H, 11-H),
3.79 (s, 2 H, 22-H), 3.69 (dd, J = 9.9, 7.0 Hz, 1 H, 1-Hb), 3.64 (dd,
EtOAc/hexanes). [α]D = +17.7 (c = 1.00, CH Cl ). IR (film): ν =
˜
2
2
3451, 2954, 2931, 2858, 2886, 1770, 1737, 1473, 1463, 1256, 1100,
J = 8.2, 3.1 Hz, 1 H, 15-H), 2.37 (dt, J = 13.1, 4.3 Hz, 1 H, 20-H), 838, 778 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 4.72 (q, J =
2.37–2.28 (m, 1 H, 9-Ha), 2.28 (d, J = 14.1 Hz, 1 H, 13-Ha), 2.17 6.0 Hz, 1 H), 4.50 (d, J = 6.0 Hz, 1 H), 3.81 (t, J = 3.6 Hz, 1 H),
(ddd, J = 13.7, 9.2, 4.8 Hz, 1 H, 20-Ha), 1.99–1.83 (m, 5 H, 2-H,
6-Ha, 8-Ha, 9-Hb, 17-Hax), 1.74–1.38 (m, 9 H, 4-Ha, 5-H, 6-Hb, 8-
Hb, 13-Hb, 17-Heq, 19-H), 1.35 (d, J = 6.8 Hz, 3 H, 41-H), 1.30 (s,
3 H, 43-H), 1.22 (s, 9 H, 1O-Si-tBu), 1.15 (s, 3 H, 42-H), 1.09 (s, 9
H, 11-OSi-tBu), 1.07 (s, 9 H, 14-OSi-tBu), 1.04 (d, J = 6.8 Hz, 1
3.79 (dd, J = 13.2, 3.6 Hz, 1 H), 3.69 (dt, J = 13.2, 3.5 Hz, 1 H),
3.72 (s, 3 H), 2.42 (dd, J = 13.3, 5.6 Hz, 1 H), 1.84 (dd, J = 13.3,
6.3 Hz, 1 H), 1.23 (s, 3 H), 0.89 (s, 9 H), 0.86 (s, 9 H), 0.08 (s, 3
H), 0.073 (s, 3 H), 0.071 (s, 3 H), 0.05 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 171.8, 87.1, 80.2, 75.9, 74.7, 63.8, 52.0,
1690
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Eur. J. Org. Chem. 2011, 1682–1694