The Journal of Organic Chemistry
Note
(d, J = 8.3 Hz, 1H), 6.19 (dd, J = 15.8,5.7 Hz, 1H), 5.27 (s, 2H), 4.36
(ddd, J = 5.7, 3.8, 1.5 Hz, 1H), 3.83 (s, 3H), 3.51 (dd, J = 5.8, 3.8 Hz,
1H), 2.96 (dd, J = 5.3, 2.1 Hz, 1H), 2.82 (dd, J = 5.8, 2.1 Hz, 1H), 2.06
(s, 3H), 1.33 (d, J = 5.3 Hz, 3H), 0.90 (s, 9H), 0.09 (s, 3H), 0.06 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 171.1, 158.4, 138.9, 132.5,
129.8, 127.9, 121.1, 118.5, 109.8, 74.8, 73.8, 59.1, 57.6, 55.7, 53.3, 25.7,
21.0, 18.1, 17.2, −4.4, −4.8; IR (neat) νmax 3451, 2924, 2853, 1734,
1579, 1470, 1380, 1360, 1251, 1100, 1023, 836 cm−1; HRMS (ESI) m/
z [M + Na]+ calcd for C23H36O6NaSi 459.2157, found 459.2173.
Synthesis of A and A1. Column-separable A and A1 (1:2) (110
mg, 92%) were prepared from the mixture 12 and 12a (120 mg, 0.275
mmol) following the same procedure described in ref 8a.
mixture was stirred for 10 min at −78 °C, the reaction mixture was
quenched with H2O. This mixture was extracted with EtOAc, dried
over Na2SO4, and concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel (50% EtOAc/hexanes) to
afford diol 14 (977 mg, 82%) as colorless oil: Rf = 0.2 (70% EtOAc/
hexanes); [α]28 = +10.0 (c 0.24, CHCl3); 1H NMR (500 MHz,
D
CDCl3) δ 7.30 (t, J = 8.0 Hz, 1H), 7.11 (d, J = 8.0 Hz, 1H), 7.00 (d, J
= 16.0 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 6.22 (dd, J = 16.0, 7.0 Hz,
1H), 5.29 (ABq, J = 12.0 Hz, 2H), 4.49 (dd, J = 7.0, 6.0 Hz, 1H), 3.85
(s, 3H), 3.81 (dd, J = 6.0, 5.0 Hz, 1H), 3.11 (m, 1H), 2.86 (dd, J = 5.0,
3.0 Hz, 1H), 2.45 (bs, 1H), 2.38 (bs, 1H), 2.05 (s, 3H), 1.32 (d, J = 5.0
Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 171.3, 158.5, 138.7, 130.6,
130.0, 129.7, 121.3, 118.9, 110.1, 73.9, 72.2, 61.5, 58.6, 57.6, 55.8, 51.9,
21.1, 17.1; IR (neat) νmax 3451, 3377, 2921, 2852, 1734, 1579, 1461,
1378, 1220, 1023, 965 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for
C17H22O6Na 345.1309, found 345.1308.
Data of A (minor): Rf = 0.3 (30% EtOAc/hexanes); [α]26
=
D
1
+25.26 (c 0.77, CHCl3); H NMR (300 MHz, CDCl3) δ 7.30 (t, J =
7.9 Hz, 1H), 7.13 (d, J = 7.9 Hz, 1H), 6.94 (d, J = 15.7 Hz, 1H), 6.84
(d, J = 7.9 Hz, 1H), 6.09 (dd, J = 15.7, 8.0 Hz, 1H), 5.25 (s, 2H), 4.29
(m, 1H), 3.97 (t, J = 5.5 Hz, 1H), 3.89 (t, J = 5.5 Hz, 1H), 3.84 (s,
3H), 3.63 (m, 1H), 2.67 (d, J = 5.5 Hz, 1H), 2.05 (s, 3H), 1.34 (d, J =
6.4 Hz, 3H), 0.92 (s, 9H), 0.11 (s, 3H), 0.10 (s, 3H); 13C NMR (75
MHz, CDCl3) δ 171.0, 158.4, 138.5, 130.8, 129.9, 129.6, 118.6, 110.0,
84.5, 79.8, 76.7, 76.2, 57.6, 55.8, 25.7, 21.0, 18.9, 18.0, −4.3, −4.9; IR
(neat) νmax 3450.9, 2925.9, 2854.4, 1733.3, 1579.9, 1467.7, 1381.6,
1253.9, 1103.4, 1023.0, 964.5, 774.1 cm−1; HRMS (ESI) calcd for
2-((E)-2-((2R,3S,4R,5S)-3,4-Dihydroxy-5-methyltetrahydro-
furan-2-yl)vinyl)-6-methoxybenzyl Acetate (15). Compound 15
(37 mg, 93%) was synthesized as a liquid from epoxide 14 (40 mg,
0.124 mmol) following the same procedure described for epoxide
opening in ref 8a: Rf = 0.3 (70% EtOAc/hexanes); [α]28 = +20.8 (c
D
0.56, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.30 (t, J = 8.3 Hz, 1H),
7.11 (d, J = 8.3 Hz, 1H), 6.98 (d, J = 15.7 Hz, 1H), 6.83 (d, J = 8.3 Hz,
1H), 6.10 (dd, J = 15.7, 7.0 Hz, 1H), 5.29 (ABq, J = 11.5 Hz, 2H), 4.33
(t, J = 7.0 Hz, 1H), 3.94 (m, 2H), 3.84 (s, 3H), 3.79 (t, J = 5.5 Hz,
1H), 2.05 (s, 3H), 1.35 (d, J = 6.2 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ158.5, 138.8, 131.2, 129.9, 129.5, 121.2, 118.9, 110.0, 84.0,
80.0, 76.2, 75.4, 57.6, 55.8, 21.1, 19.1; IR (neat) νmax 3428, 2921, 2851,
1733, 1580, 1462, 1379, 1266, 1078, 966 cm−1; HRMS (ESI) m/z [M
+ Na]+ calcd for C17H22O6Na 345.1308, found 345.1308.
C23H36O6NaSi [M + Na]+ 439.2175, found 439.2173.
Data of A1 (major): [α]28 = +38.02 (c 0.40, CHCl3); H NMR
1
D
(500 MHz, CDCl3) δ 7.28 (t, J = 7.9 Hz, 1H), 7.17 (d, J = 7.9 Hz,
1H), 6.83 (d, J = 7.9 Hz, 1H), 6.81 (d, J = 15.8 Hz, 1H), 6.28 (dd, J =
15.8, 8.0 Hz, 1H), 5.26 (ABq, J = 16.3, 11.6 Hz, 2H), 4.62 (m, 1H),
4.30 (t, J = 5.0 Hz, 1H), 3.98 (m, 1H), 3.84 (s, 3H), 3.74 (m, 1H),
2.34 (d, J = 8.3 Hz, 1H), 2.06 (s, 3H), 1.32 (d, J = 6.4 Hz, 3H), 0.91
(s, 9H), 0.11 (s, 3H), 0.02 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
171.2, 158.4, 138.4, 129.7, 129.5, 121.1, 118.4, 109.8, 81.5, 78.3, 77.9,
74.7, 57.5, 55.8, 25.7, 21.0, 18.8, 18.2, −4.5, −4.9; IR (neat) νmax
3448.6, 2928.0, 2855.5, 1733.6, 1579.9, 1468.8, 1380.9, 1257.4, 1083.4,
967.9, 839 cm−1; HRMS (ESI) calcd for C23H36O6NaSi [M + Na]+
439.2159, found 439.2173.
Varitriol (1). (+)-Varitriol (1) (15.3 mg, 88%) was synthesized as a
solid from compound 15 (20 mg, 0.062 mmol) following the acetyl
deprotection reported in ref 8a: Rf = 0.3 (EtOAc); [α]30 = +23.8 (c
D
1
0.26, CH3OH); H NMR (500 MHz, CD3COCD3) δ 7.23 (t, J = 8.0
Hz, 1H), 7.13 (d, J = 15.8 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 6.90 (d, J
= 8.0 Hz, 1H), 6.21 (dd, J = 15.8, 6.7 Hz, 1H), 4.72 (s, 2H), 4.29 (t, J
= 6.7 Hz, 1H), 4.23 (brs, 1H), 4.03 (brs, 1H), 3.91 (m, 1H), 3.84 (m,
1H), 3.83 (s, 3H), 3.70 (m, 1H), 3.65 (brs, 1H), 1.28 (d, J = 6.2 Hz,
3H); 13C NMR (125 MHz, CD3COCD3) δ 158.9, 139.0, 132.4, 129.4,
129.3, 128.0, 119.3, 110.6, 85.3, 80.0, 77.2, 76.5, 56.0, 55.5, 19.5; IR
(neat) νmax 3355, 2920, 1578, 1354, 1219, 1088; HRMS (ESI) m/z [M
+ Na]+ calcd for C15H20O5Na 303.1199, found 303.1202.
Synthesis of 1 and 1a. Independently, 1 (14.5 mg, 82%) and 1a
(27.0 mg, 81%) were synthesized from A (37 mg, 0.085 mmol) and
A1 (70 mg, 0.160 mmol), respectively, by following the procedures
described for deprotection of silyl and acetyl reported in ref 8a.
Data of 1a: Rf = 0.3 (EtOAc); [α]28 = +6.23 (c 1.38, CH3OH);
D
1H NMR (500 MHz, CD3CN) δ 7.24 (t, J = 7.9 Hz, 1H), 7.14 (d, J =
Varioxirane (2). Compound 2 (70 mg, 81%) was synthesized as a
7.9 Hz, 1H), 6.96 (d, J = 15.8 Hz, 1H), 6.89 (d, J = 7.9 Hz, 1H), 6.24
(dd, J = 15.8, 7.1 Hz, 1H), 4.66 (d, J = 5.0 Hz, 2H), 4.59 (m, 1H), 4.08
(m, 1H), 3.87 (m, 1H), 3.82 (s, 3H), 3.75 (m, 1H), 3.32 (bd, J = 3.9
Hz, 1H), 3.25 (bd, J = 7.3 Hz, 1H) 2.94 (t, J = 3.9 Hz, 1H), 1.23 (d, J
= 6.1 Hz, 3H); 13C NMR (125 MHz, CD3CN) δ 158.4, 138.4, 130.1,
129.4, 129.2, 127.0, 119.0, 110.3, 81.3, 78.6, 77.7, 74.1, 55.8, 55.1, 18.7;
IR (neat) νmax 3381.5, 2924.7, 2854.7, 1578.5, 1470.8, 1375.7, 1265.1,
1135.0, 1075.2, 1016.4, 975.3, 784.8; HRMS (ESI) calcd for
C15H20O5Na [M + Na]+ 303.1197, found 303.1202.
2-((S,E)-4-Hydroxy-4-((2R,3R)-3-methyloxiran-2-yl)-3-oxo-
but-1-enyl)-6-methoxybenzyl Acetate (13). Compound 13 (1.84
g, 81%) was synthesized as a solid from 4 (3.1 g, 7.1 mmol) following
the TBS deprotection reported in ref 2k: Rf = 0.3 (40% EtOAc/
hexanes); mp 110−112 °C; [α]28D = +23.3 (c 0.51, CHCl3); 1H NMR
(500 MHz, CDCl3) δ 8.17 (d, J = 16.0 Hz, 1H), 7.37 (t, J = 7.8, Hz,
1H), 7.32 (d, J = 7.8 Hz, 1H), 7.00 (d, J = 16.0 Hz, 1H), 6.99 (d, J =
7.8 Hz, 1H), 5.35 (ABq, J = 12 Hz, 2H), 4.07 (d, J = 7.6 Hz, 1H), 3.87
(s, 3H), 3.17 (qd, J = 5.3, 2.0 Hz, 1H), 2.70 (dd, J = 7.6, 2.0 Hz, 1H),
2.06 (s, 3H), 1.38 (d, J = 5.3 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
197.9, 170.9, 158.6, 143.1, 135.8, 130.1, 124.0, 123.8, 119.1, 112.9,
76.6, 58.3, 57.0, 55.9, 54.2, 20.9, 17.1; IR (neat) νmax 3450, 2923, 2851,
1733, 1689, 1610, 1576, 1472, 1440, 1379, 1260, 1099, 1081, 1023,
633 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for C17H20O6Na
343.1150, found 343.1152.
liquid from compound 14 (100 mg, 0.31 mmol) following the same
procedure described in ref 8a: Rf = 0.3 (EtOAc); [α]30 = −24.61 (c
D
1
0.13, CHCl3); H NMR (400 MHz, CDCl3) δ 7.26 (d, J = 8.4 Hz,
1H), 7.25 (d, J = 15.9 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 6.84 (d, J =
8.4 Hz, 1H), 6.21 (dd, J = 15.9, 6.7 Hz, 1H), 4.80 (s, 2H), 4.50 (dd, J
= 6.7, 4.2 Hz, 1H), 3.86 (s, 3H), 3.81 (t, J = 4.2 Hz, 1H), 3.10 (qd, J =
5.0, 2.5 Hz, 1H), 2.86 (dd, J = 4.2, 2.5 Hz, 1H), 2.55 (brs, 1H), 1.70
(bs, 2H), 1.31 (d, J = 5.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
157.7, 137.7, 130.5, 129.3, 128.9, 125.9, 119.1, 109.7, 73.8, 72.7, 58.7,
55.8, 55.6, 52.3, 17.1; IR (neat) νmax 3454, 3376, 2923, 2853, 1577,
1469, 1260, 1074, 998 cm−1; HRMS (ESI) m/z [M + Na]+ calcd for
C15H20O5Na 303.1204, found 303.1202.
Triacetylvarioxirane (16). Compound 16 (42 mg, 95%) was
synthesized as a colorless oil from compound 2 (30 mg, 0.11 mmol),
Ac2O (0.04 mL, 0.42 mmol), and Et3N (0.09 mL, 0.64 mmol)
following the same procedure described for acetyl in ref 8a: Rf = 0.5
1
(30% EtOAc/hexanes); [α]30 = −32.9 (c 0.19, CHCl3); H NMR
D
(300 MHz, CDCl3) δ 7.31 (t, J = 8.3 Hz, 1H), 7.11 (d, J = 8.3 Hz,
1H), 6.98 (d, J = 15.8 Hz, 1H), 6.86 (d, J = 8.3 Hz, 1H), 6.14 (dd, J =
15.8, 7.5 Hz, 1H), 5.70 (ddd, J = 7.5, 3.7, 1.5 Hz, 1H), 5.26 (s, 2H),
4.90 (dd, J = 6.0, 3.7 Hz, 1H), 3.84 (s, 3H), 3.03 (dq, J = 5.3, 2.2 Hz,
1H), 2.85 (dd, J = 6.0, 2.2 Hz, 1H), 2.12 (s, 3H), 2.09 (s, 3H), 2.07 (s,
3H), 1.30 (d, J = 5.3 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 171.0,
169.8, 169.7, 158.4, 138.2, 131.9, 131.7, 129.9, 125.8, 118.8, 110.4,
73.7, 73.1, 57.5, 55.9, 55.8, 52.9, 21.0, 20.9, 20.8, 17.1; IR (neat) νmax
2922, 2851, 1741, 1579, 1469,1373,1224,1024 cm−1; HRMS (ESI) m/
z [M + Na]+ calcd for C21H26O8Na 429.1503, found 429.1519.
2-((3R,4R,E)-3,4-Dihydroxy-4-((2R,3R)-3-methyloxiran-2-yl)-
but-1-enyl)-6-methoxybenzyl Acetate (14). To a solution of
ketone 13 (1.2 g, 3.7 mmol) in ether (20 mL) was slowly added
LiEt3BH (5.6 mL, 1.0 M in THF, 5.6 mmol) at −78 °C. After the
E
dx.doi.org/10.1021/jo4011766 | J. Org. Chem. XXXX, XXX, XXX−XXX