The Journal of Organic Chemistry
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petroleum ether); [α]D25 +3.8 (c 1.0, CHCl3); H NMR (200 MHz,
CDCl3) δ 1.20 (d, J = 6.4 Hz, 3H), 1.75−1.97 (m, 2H), 2.11−2.43 (m,
2H), 3.56 (dd, J = 3.7, 6.2 Hz, 1H), 3.68−3.75 (m, 1H), 3.78 (s, 3H),
3.79 (s, 6H), 3.82−3.92 (m, 1H), 4.24 (d, J = 11.3 Hz, 1H), 4.28 (d, J
= 11.4 Hz, 1H), 4.51 (d, J = 11.4 Hz, 1H), 4.53 (d, J = 11.3 Hz, 1H),
4.61 (d, J = 11.3 Hz, 1H), 4.67 (d, J = 11.2 Hz, 1H), 4.99 (dq, J = 3.8,
6.4 Hz, 1H), 5.17−5.34 (m, 4H), 5.69 (ddd, J = 7.6, 11.0, 16.4 Hz,
1H), 5.83 (ddd, J = 8.1, 10.6, 16.9 Hz, 1H), 6.82−6.86 (m, 6H), 7.21−
7.29 (m, 6H); 13C NMR (50 MHz, CDCl3) δ 14.7, 30.3, 30.5, 55.2
(3C), 69.8, 70.1, 71.0, 74.6, 79.1, 81.5, 82.6, 113.6 (2C), 113.6 (2C),
113.7 (2C), 117.6, 119.1, 129.3 (2C), 129.4 (2C), 129.6 (2C), 130.3,
130.5, 130.7, 135.2, 138.3, 159.0, 159.0, 159.1, 172.5 ppm; ESI-MS
627.68 (100%, [M + Na]+); HRMS (m/z) calcd for C36H44O8Na,
627.2934; found, 627.2948.
1
9.0, 9.6 Hz, 2H), 5.01 (dq, J = 6.9, 9.6 Hz, 1H), 5.42 (dd, J = 2.3, 15.4
Hz, 1H), 5.82 (ddd, J = 1.5, 9.8, 15.3 Hz, 1H); 13C NMR (125 MHz,
CDCl3) δ −5.0, −5.0, −3.8, −3.3, 18.1, 18.3, 18.5, 25.8 (3C), 26.2
(3C), 27.9, 32.6, 39.3, 68.5, 68.5, 76.1, 84.2, 130.2, 132.4, 175.3 ppm;
ESI-MS 545.96 (100%, [M + Na]+); HRMS (m/z) calcd for
C23H46O7SSi2Na, 545.2400; found, 545.2408.
(1R,2S,7S,10S,E)-7-Hydroxy-2-methyl-3,11-dioxabicyclo-
[8.1.0]undec-8-en-4-one (4). To a solution of 7 (30 mg, 0.06
mmol) in dry THF (1 mL), a 1 M solution of TBAF in THF (172 μL,
0.17 mmol) was added at 0 °C, and the contents were stirred at rt for
10 h. To this was added sat. NH4Cl, and the aqueous layer was
extracted with EtOAc. The combined organic layer was dried
(Na2SO4) and concentrated. The residue was purified on a silica gel
column (40% EtOAc in petroleum ether) to afford 4 (9 mg, 79%) as a
yellow oil. Rf 0.4 (60% EtOAc in petroleum ether); [α]D25 +9.1 (c 0.2,
CHCl3); IR (CHCl3) ν 3336, 2924, 1733, 1602, 1542, 1456, 1270,
1121 cm−1; HRMS (m/z) calcd for C10H14O4Na, 221.0790; found,
221.0786.
(5R,8S,9R,10S,E)-5,8,9-Trihydroxy-10-methyl-3,4,5,8,9,10-
hexahydro-2H-oxecin-2-one (22). The same procedure as in the
preparation of 9 was used with the diene 21 (100 mg, 0.16 mmol) to
procure the impure macrolide. The above macrolide was suspended at
0 °C in TFA (2 mL) and stirred for 2 h. The reaction mixture was
concentrated under reduced pressure, and the residue was purified by
column chromatography (70 → 100% EtOAc in petroleum ether) to
obtain 22 (10 mg, 28%) as a yellow viscous liquid. Rf 0.2 (85% EtOAc
in petroleum ether); [α]D25 −20.9 (c 0.5, MeOH); 1H NMR (400
MHz, CDCl3) δ 1.27 (d, J = 6.4 Hz, 3H), 1.75−1.85 (m, 1H), 1.91−
1.98 (m, 1H), 2.05 (dt, J = 1.8, 13.6 Hz, 1H), 2.29 (ddd, J = 2.4, 6.3,
13.8 Hz, 1H), 3.21 (t, J = 9.1 Hz, 1H), 3.67 (t, J = 9.1 Hz, 1H), 4.02
(ddd, J = 4.9, 9.9, 14.2 Hz, 1H), 4.84 (dq, J = 6.4, 9.7 Hz, 1H), 5.33
(dd, J = 9.1, 15.6 Hz, 1H), 5.63 (dd, J = 9.6, 15.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 18.4, 32.3, 33.8, 71.4, 75.3, 77.5, 77.8, 133.5,
133.9, 176.0 ppm; HRMS (m/z) calcd for C10H16O5Na, 239.0895;
found, 239.0871.
Spectral Data of Major Conformer: 1H NMR (400 MHz, CDCl3)
δ 1.40 (d, J = 6.8 Hz, 3H), 1.89−2.07 (m, 2H,), 2.14−2.26 (m, 1H,),
2.49 (t, J = 14.0 Hz, 1H,), 3.03 (dd, J = 2.7, 4.1 Hz, 1H), 3.69 (t, J =
4.6 Hz, 1H), 4.54 (br s, 1H), 5.33 (dq, J = 2.7, 6.8 Hz, 1H), 5.68 (ddd,
J = 1.1, 3.2, 17.1 Hz, 1H), 5.94 (ddd, J = 1.1, 4.8, 17.1 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 16.3, 27.7, 33.4, 55.9, 57.3, 65.1, 68.1,
126.2, 134.0, 174.6 ppm.
Spectral Data of Minor Conformer: 1H NMR (400 MHz, CDCl3)
δ 1.46 (d, J = 6.8 Hz, 3H), 1.89−2.07 (m, 2H, merged with major
conformer signal), 2.14−2.26 (m, 1H, merged with major conformer
signal), 2.44−2.53 (m, 1H, merged with major conformer signal), 2.90
(dd, J = 1.6, 4.3 Hz, 1H), 3.53 (dt, J = 1.4, 4.3 Hz, 1H), 4.20 (dt, J =
4.7, 8.3 Hz, 1H), 5.27 (dq, J = 1.5, 6.8 Hz, 1H), 5.53 (dd, J = 1.1, 16.0
Hz, 1H), 5.75 (ddd, J = 1.1, 8.7, 15.9 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 17.7, 31.7, 32.5, 55.8, 57.6, 66.2, 72.7, 120.6, 135.3, 172.1
ppm.
(1R,2S,7S,10S,E)-2-Methyl-4-oxo-3,11-dioxabicyclo[8.1.0]-
undec-8-en-7-yl-4-nitrobenzoate (4-Bz). At 0 °C, to a solution of
p-nitrobenzoic acid (11 mg, 65 μmol) and DMF (cat.) in DCM (1
mL) was added oxalyl chloride (4 μL, 60 μmol), and the content were
stirred at rt for 6 h. The excess of oxalyl chloride was removed under
an argon atmosphere. The crude product was dissolved in dry DCM,
cooled to 0 °C, and treated with a solution of Et3N (14 μL, 100 μmol)
and alcohol 4 (10 mg, 50 μmol) in DCM (0.5 mL), and the reaction
mixture was stirred at rt for 10 h. To this was added water, and the
aqueous layer was extracted with DCM. The combined organic layer
was dried (Na2SO4) and concentrated. The crude product was purified
on a silica gel column (20 → 22% EtOAc in petroleum ether) to afford
4-Bz (14 mg, 81%) as a yellow oil. Rf 0.5 (40% EtOAc in petroleum
ether); [α]D25 +27.9 (c 0.7, CHCl3); HRMS (m/z) calcd for
C17H17NO7Na, 370.0903; found, 370.0931.
(5R,8S,9S,10S,E)-5,8-Bis(tert-butyldimethylsilyloxy)-9-hy-
droxy-10-methyl-3,4,5,8,9,10-hexahydro-2H-oxecin-2-one
(23). The same procedure as in the preparation of 20 was used with
the triol 22 (25 mg, 0.12 mmol) to procure 23 (40 mg, 77%) as a
yellow oil. Rf 0.6 (10% EtOAc in petroleum ether); [α]D25 −12.4 (c =
1
0.5 in CHCl3); H NMR (400 MHz, CDCl3) δ 0.02 (s, 3H), 0.03 (s,
3H), 0.05 (s, 3H), 0.08 (s, 3H), 0.85 (s, 9H), 0.87 (s, 9H), 1.30 (d, J =
6.4 Hz, 3H), 1.81−1.87 (m, 1H), 1.90−2.03 (m, 2H), 2.21−2.32 (m,
1H), 2.82 (s, 1H), 3.28 (dd, J = 8.6, 9.4 Hz, 1H), 3.78 (t, J = 8.6 Hz,
1H), 3.99 (dt, J = 5.4, 9.1 Hz, 1H), 4.95 (dq, J = 6.4, 9.5 Hz, 1H), 5.41
(dd, J = 8.3, 15.7 Hz, 1H), 5.48 (dd, J = 8.6, 15.7 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ −4.8, −4.8, −4.6, −3.6, 18.0, 18.1, 18.1, 25.7
(3C), 25.8 (3C), 31.4, 34.00, 69.5, 75.1, 76.4, 78.3, 131.1, 134.8, 173.8
ppm; ESI-MS 467.34 (100%, [M + Na]+); HRMS (m/z) calcd for
C22H44O5Si2Na, 467.2625; found, 467.2603.
(2S,3S,4S,7R,E)-4,7-Bis(tert-butyldimethylsilyloxy)-2-methyl-
10-oxo-3,4,7,8,9,10-hexahydro-2H-oxecin-3-yl Methanesulfo-
nate (24). The same procedure as in the preparation of 7 was used
with the alcohol 23 (20 mg, 0.05 mmol), affording 24 (20 mg, 85%) as
a yellow oil. Rf 0.3 (10% EtOAc in petroleum ether); [α]D25 −7.6 (c 1.4,
Spectral Data of Major Conformer: 1H NMR (400 MHz, CDCl3)
δ 1.43 (d, J = 6.8 Hz, 3H), 2.21−2.30 (m, 2H), 2.37−2.49 (m, 2H),
3.05 (dd, J = 2.5, 4.1 Hz, 1H), 3.69 (tt, J = 1.3, 4.6 Hz, 1H), 5.42 (dq, J
= 2.4, 6.8 Hz, 1H), 5.67 (br s, 1H), 5.74 (dd, J = 1.3, 17.2 Hz, 1H),
5.86 (dd, J = 4.6, 17.1 Hz, 1H), 8.24 (d, J = 8.9 Hz, 2H), 8.30 (d, J =
8.9 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 16.4, 28.9, 31.5, 55.5,
57.5, 65.3, 75.9, 123.0 (2C), 127.5, 128.9, 130.8 (2C), 130.8, 135.3,
163.8, 173.8 ppm.
1
CHCl3); H NMR (400 MHz, CDCl3) δ 0.02 (s, 3H), 0.04 (s, 3H),
0.06 (s, 3H), 0.07 (s, 3H), 0.85 (s, 9H), 0.87 (s, 9H), 1.36 (d, J = 6.6
Hz, 3H), 1.82−1.91 (m, 2H), 1.98 (dt, J = 2.6, 12.7 Hz, 1H), 2.26−
2.36 (m, 1H), 3.07 (s, 3H), 4.01 (ddd, J = 5.5, 8.2, 9.5 Hz, 1H), 4.07
(dd, J = 8.1, 8.7 Hz, 1H), 4.39 (dd, J = 8.7, 9.8 Hz, 1H), 4.98 (dq, J =
6.6, 9.8 Hz, 1H), 5.37 (dd, J = 8.1, 15.9 Hz, 1H), 5.45 (dd, J = 8.8, 15.9
Hz, 1H); 13C NMR (100 MHz, CDCl3) δ −4.7, −4.7, −3.9, −3.2,
18.0, 18.2, 18.4, 25.6 (3C), 26.1 (3C), 31.2, 33.5, 39.3, 68.5, 75.1, 75.8,
84.1, 130.6, 134.2, 173.8 ppm; ESI-MS 545.33 (100%, [M + Na]+);
HRMS (m/z) calcd for C23H46O7SSi2Na, 545.2400; found, 545.2408.
(+)-Stagonolide D (25). The same procedure as in the preparation
of 4 was used with 24 (20 mg, 0.04 mmol) to procure 25 (6 mg, 76%)
as a white crystalline solid. Rf 0.4 (60% EtOAc in petroleum ether);
mp 78−81 °C; [α]D25 +76.8 (c 0.2, CHCl3); IR (CHCl3) ν 3435, 2925,
2851, 1731, 1635, 1456, 1384, 1089, 728 cm−1; HRMS (m/z) calcd for
C10H15O4, 199.0970; found, 199.0961.
Spectral Data of Minor Conformer: 1H NMR (400 MHz, CDCl3)
δ 1.49 (d, J = 6.8 Hz, 3H), 2.11−2.20 (m, 2H), 2.30−2.36 (m, 1H),
2.52−2.58 (m, 1H), 2.94 (dd, J = 1.4, 4.3 Hz, 1H), 3.58 (br d, J = 4.2
Hz, 1H), 5.34 (dq, J = 1.3, 6.8 Hz, 1H), 5.48 (dt, J = 4.2, 8.2 Hz, 1H),
5.74 (dd, J = 1.1, 17.1 Hz, 1H), 5.90 (dd, J = 4.1, 17.0 Hz, 1H), 8.20
(d, J = 8.8 Hz, 2H), 8.28 (d, J = 8.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ 17.1, 30.2, 31.4, 55.7, 57.7, 62.2, 75.7, 122.7, 123.6 (2C),
130.7 (2C), 130.8, 130.8, 135.5, 163.3, 171.9 ppm.
(R)-((2S,3S,4S)-3,4-Bis(4-methoxybenzyloxy)hex-5-en-2-yl)-
4-(4-methoxybenzyloxy)hex-5-enoate (21). The coupling of acid
(R)-11 (1.0 g, 4.0 mmol) and the alcohol 12 (1.5 g, 4.0 mmol) was
carried out according to the procedure used for the preparation of 10
to afford 21 (1.89 g, 78%) as a yellow oil. Rf 0.5 (20% EtOAc in
Spectral Data of Major Conformer: 1H NMR (400 MHz, CDCl3)
δ 1.38 (d, J = 6.8 Hz, 3H), 1.98−2.14 (m, 3H), 2.28 (ddd, J = 1.9, 8.3,
14.2 Hz, 1H), 3.05 (dd, J = 2.6, 4.1 Hz, 1H), 3.65 (br t, J = 4.6 Hz,
2174
dx.doi.org/10.1021/jo202138g | J. Org. Chem. 2012, 77, 2169−2175