7
3. Representative General Procedure (Note: All the
(ESIMS) calcd for C16H15O6 [M+H]+ : m/z 303.0869; found:
303.0874.
ACCEPTED MANUSCRIPT
reagents and solvents were added in an Ace pressure tube inside
the glove box and it was sealed with cap before heating). An
oven dried 15 mL Ace pressure tube (Sigma-Aldrich) was
charged with aryne precursor silyl aryl triflate (0.22 mmol) and
substituted DMAD (0.2 mmol) to which anhydrous THF (5 mL)
and CsF (0.4 mmol) were added, the tube was sealed with the cap
and was placed in a pre-heated oil bath at 100 oC and was stirred
for 12 h. The reaction mixture was cooled to room temperature
and was filtered through celite with the aid of EtOAc, volatile
components were removed under reduced pressure using rotary
evaporator and the resulted crude compound was purified by
silica gel flash column chromatography to give the substituted
naphthoresorcinols 4f-p.
Methyl 2,4-dihydroxy-3-methyl-1-naphthoate (4j): By
following the general procedure 3 using methyl-DMAD 2c and
aryne precursor 1a, compound 4j (34.3 mg, 74%) was prepared
as white solid; Rf = 0.5 (20% EtOAc + Hexane); mp 112-114 oC;
1H NMR (500 MHz, CDCl3) δ 13.15 (s, 1H), 8.73 (d, J = 8.8 Hz,
1H), 8.15 (d, J = 9.1 Hz, 1H), 7.53 (t, J = 8.5 Hz, 1H), 7.36 (t, J =
8.0 Hz, 1H), 5.75 (s, 1H), 4.08 (s, 3H), 2.30 (s, 3H); 13C NMR
(126 MHz, CDCl3) δ 173.4, 165.4, 155.1, 131.3, 128.3, 125.2,
123.1, 121.9, 120.0, 107.7, 98.4, 52.2, 8.3; IR (neat): υmax 705,
746, 1258, 1329, 1462, 1630, 2678, 3052, 3300 cm−1; HRMS
(ESIMS) calcd for C13H12O4Na [M+Na]+: m/z 255.0269; found:
255.0257.
Methyl 3-allyl-2,4-dihydroxy-1-naphthoate (4f): By
following the general procedure 3 using dimethyl 2-allyl-3-
oxopentanedioate 2b (allyl-DMAD) and aryne precursor 1a ,
compound 4f (36.1 mg, 70%) was prepared as a semi-solid; Rf =
0.5 (20% EtOAc + Hexane); 1H NMR (400 MHz, CDCl3) δ 13.19
(s, 1H), 8.72 (d, J = 8.8 Hz, 1H), 8.17 (dd, J = 8.3, 1.0 Hz, 1H),
7.53 (ddd, J = 8.6, 6.9, 1.5 Hz, 1H), 7.35 (ddd, J = 8.1, 6.9, 1.0
Hz, 1H), 6.25 (s, 1H), 6.05 (ddt, J = 16.2, 10.1, 6.1 Hz, 1H),
5.36–5.14 (m, 2H), 4.07 (s, 3H), 3.67 (dt, J = 6.1, 1.6 Hz, 2H);
13C NMR (101 MHz, CDCl3) δ 173.4, 164.8, 156.8, 135.4, 131.9,
128.7, 125.1, 123.2, 122.3, 120.5, 117.1, 109.1, 98.5, 52.2, 27.7;
IR (neat): υmax 803, 855, 1029, 1095, 1171, 1238, 1440, 1464,
1518, 1635, 1713, 2855, 2927, 3390 cm−1; HRMS (ESIMS) calcd
for C15H15O4 [M+H]+ : m/z 259.0970; found: 259.0981.
Methyl 2,4-dihydroxy-3,6,7-trimethyl-1-naphthoate (4k):
By following the general procedure 3 using methyl-DMAD 2c
and aryne precursor 1b, compound 4k (37.4 mg, 72%) was
prepared as a sticky pale yellow oil. Rf = 0.5 (20% EtOAc +
1
Hexane); H NMR (500 MHz, CDCl3) δ 13.04 (s, 1H), 8.48 (s,
1H), 7.85 (s, 1H), 5.64 (s, 1H), 4.07 (s, 3H), 2.43 (s, 3H), 2.39 (s,
3H), 2.27 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 173.4, 164.8,
154.7, 138.0, 132.4, 130.0, 125.3, 121.5, 118.6, 106.8, 97.8, 52.1,
21.0, 19.9, 8.3; IR (neat): υmax 707, 751, 1025, 1247, 1325, 1666,
2330, 2981, 3082, 3410 cm−1; HRMS (ESIMS) calcd for
C15H17O4 [M+H]+ : m/z 261.1127; found: 261.1126.
Methyl
2,4-dihydroxy-6,7-dimethoxy-3-methyl-1-
naphthoate (4l): By following the general procedure 3 using
methyl-DMAD 2c and aryne precursor 1d, compound 4l (39.7
mg, 68%) was prepared as a white solid. Rf = 0.3 (20% EtOAc +
Methyl 3-allyl-2,4-dihydroxy-6,7-dimethyl-1-naphthoate
(4g): By following the general procedure 3 using allyl-DMAD
2b and aryne precursor 1b, compound 4g (48.6 mg, 85%) was
o
1
Hexane); mp: 135-137 C; H NMR (400 MHz, CDCl3) δ 12.90
(s, 1H), 8.20 (s, 1H), 7.48 (s, 1H), 5.66 (s, 1H), 4.07 (s, 3H), 4.00
(s, 3H), 3.99 (s, 3H), 2.27 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
173.1, 163.9, 154.4, 150.8, 146.7, 127.2, 114.7, 105.9, 105.8,
101.8, 98.0, 55.8, 55.6, 52.1, 8.2; IR (neat): υmax 705, 764, 1176,
1285, 1368, 1560, 1652, 2932, 3426 cm−1; HRMS (ESIMS) calcd
for C15H17O6 [M+H]+ : m/z 293.1025; found: 293.1025.
1
prepared as semi-solid. Rf = 0.4 (20% EtOAc + Hexane); H
NMR (500 MHz, CDCl3) δ 13.01 (s, 1H), 8.39 (s, 1H), 7.81 (s,
1H), 6.11 – 5.88 (m, 2H), 5.16 (ddd, J = 13.7, 11.6, 1.5 Hz, 2H),
3.99 (s, 3H), 3.57 (dt, J = 5.9, 1.4 Hz, 2H), 2.35 (s, 3H), 2.31 (s,
3H); 13C NMR (126 MHz, CDCl3) δ 173.4, 164.2, 156.4, 138.4,
135.6, 132.5, 130.5, 125.5, 121.9, 119.1, 116.8, 108.2, 97.9, 52.1,
27.6, 21.0, 19.8; IR (neat): υmax 820, 877, 944, 1226, 1359, 1435,
1571, 1631, 2955, 3495 cm−1; HRMS (ESIMS) calcd for
C17H19O4 [M+H]+ : m/z 287.1283; found: 287.1284.
Methyl
2,4-dihydroxy-3-(3-methylbut-2-en-1-yl)-1-
naphthoate (4m): By following the general procedure 3 using
prenyl-DMAD 2d and aryne precursor 1a, compound 4m (40.6
mg, 71%) was prepared as a white solid. Rf = 0.5 (20% EtOAc +
Methyl 3-allyl-2,4-dihydroxy-6,7-dimethoxy-1-naphthoate
(4h): By following the general procedure 3 using allyl-DMAD
2b and aryne precursor 1d, compound 4h (49.6 mg, 78%) was
prepared as a white solid. Rf = 0.5 (30% EtOAc + Hexane); mp
159-161 oC; 1H NMR (400 MHz, CDCl3) δ 12.92 (s, 1H), 8.22 (s,
1H), 7.50 (s, 1H), 6.19 (s, 1H), 6.06 (ddd, J = 23.3, 11.1, 6.1 Hz,
1H), 5.35 – 5.19 (m, 2H), 4.08 (s, 3H), 4.01 (s, 3H), 3.99 (s, 3H),
3.67 (dt, J = 6.1, 1.7 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ
173.1, 163.4, 156.0, 151.1, 146.8, 135.8, 127.9, 117.0, 115.2,
107.3, 105.8, 101.9, 98.1, 55.8, 55.6, 52.2, 27.7; IR (neat): υmax
796, 857, 989, 1180, 1260, 1324, 1438, 1517, 1632, 2955, 3006,
3472 cm−1; HRMS (ESIMS) calcd for C17H19O6 [M+H]+: m/z
319.1182; found: 319.1179.
o
1
Hexane); mp: 72-74 C; H NMR (300 MHz, CDCl3) δ 13.22 (s,
1H), 8.71 (d, J = 8.8 Hz, 1H), 8.15 (dd, J = 8.3, 0.8 Hz, 1H), 7.52
(ddd, J = 8.6, 6.9, 1.4 Hz, 1H), 7.38–7.29 (m, 1H), 6.74 (s, 1H),
5.36 (t, J = 7.2 Hz, 1H), 4.07 (s, 3H), 3.62 (d, J = 7.2 Hz, 2H),
1.89 (s, 3H), 1.82 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 174.4,
165.9, 158.0, 138.2, 132.6, 129.5, 126.0, 124.0, 123.2, 122.0,
121.6, 111.6, 99.2, 53.1, 26.9, 23.6, 19.0; IR (neat): υmax 755,
1230, 1349, 1447, 1643, 2322, 2860, 2925, 3508, 3606 cm−1;
HRMS (ESIMS) calcd for C17H19O4 [M+H]+: m/z 287.1283;
found: 287.1291.
Methyl 2,4-dihydroxy-6,7-dimethyl-3-(3-methylbut-2-en-1-
yl)-1-naphthoate (4n): By following the general procedure 3
using prenyl-DMAD 2d and aryne precursor 1b, compound 4n
(47.7 mg, 76%) was prepared as a white solid. Rf = 0.5 (20%
EtOAc + Hexane); mp: 101-103 oC; 1H NMR (400 MHz, CDCl3)
δ 13.10 (s, 1H), 8.45 (s, 1H), 7.87 (s, 1H), 6.64 (s, 1H), 5.45–5.27
(m, 1H), 4.06 (s, 3H), 3.59 (d, J = 7.2 Hz, 2H), 2.42 (s, 3H), 2.37
(s, 3H), 1.88 (s, 3H), 1.81 (d, J = 1.2 Hz, 3H); 13C NMR (101
MHz, CDCl3) δ 173.5, 164.3, 156.6, 138.2, 136.9, 132.3, 130.3,
125.2, 121.9, 121.3, 119.2, 109.7, 97.6, 52.0, 25.9, 22.6, 21.0,
19.8, 18.0; IR (neat): υmax 796, 1034, 1138, 1266, 1600, 1681,
2985, 3320 cm−1; HRMS (ESIMS) calcd for C19H23O4 [M+H]+:
Methyl 7-allyl-6,8-dihydroxynaphtho[2,3-d][1,3]dioxole-5-
carboxylate (4i): By following the general procedure 3 using
allyl-DMAD 2b and aryne precursor 1f, compound 4i (45.9 mg,
76%) was prepared as a pale yellow powder. Rf = 0.4 (30%
o
1
EtOAc + Hexane); mp 168-170 C; H NMR (500 MHz, CDCl3)
δ 12.92 (s, 1H), 8.16 (s, 1H), 7.51 (s, 1H), 6.13 (s, 1H), 6.08-6.00
(m, 1H), 6.04 (s, 2H), 5.48 – 5.07 (m, 2H), 4.05 (s, 3H), 3.64 (d,
J = 6.0 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 173.2, 163.3,
156.2, 149.9, 145.0, 135.7, 129.3, 117.1, 116.3, 107.6, 103.3,
101.2, 99.6, 99.0, 52.2, 27.7; IR (neat): υmax 794, 861, 1186,
1269, 1343, 1483, 1571, 1623, 2959, 3011, 3465 cm−1; HRMS
.