Synthesis of 2,3-Dihydrobenzofurans
J . Org. Chem., Vol. 62, No. 20, 1997 6983
The data for 15a a : 1H NMR 7.12 (br d, 1, J ) 7.4), 7.09 (br
dd, 1, J ) 8.0, 7.4), 6.79 (br dd, 1, J ) 7.4, 7.4), 6.74 (br d, 1,
J ) 8.0), 2.96 (s, 2), 1.85-1.40 (m, 10); 13C NMR 158.9, 127.8,
126.8, 125.1, 119.7, 109.5, 88.4, 41.0, 37.2 (2 C), 25.2, 23.1 (2
C); IR (neat) 1597, 1481, 1240, 747. The data are identical to
those previously reported.5
Oxid a tive Cycloa d d ition of 3-Meth yl-2-cycloh exen on e
(1b) w ith 7a in Ben zen e. A solution of 1b (101 mg, 0.92
mmol), 7a (176 mg, 1.84 mmol), and Mn(OAc)3 (852 mg, 3.67
mmol) in 10 mL of benzene was refluxed at 80 °C for 3 d.
Normal workup and flash chromatography on silica gel (50:1
hexane/EtOAc, 10:1 hexane/EtOAc, then 3:1 hexane/EtOAc)
gave 58 mg (31%) of 15ba , followed by 22 mg (12%) of 6-(1-
cyclohexenylmethyl)-3-methyl-2-cyclohexenone (12ba ) and 23
mg (23%) of recovered 1b.
1.51 (m, 10); 13C NMR 158.5, 134.9, 127.7, 125.6, 120.7, 106.7,
88.1, 39.9, 37.3, 25.2, 23.1, 18.8; IR (neat) 1614, 1599, 1460,
1275, 1023, 932, 767.
Oxid a tive Cycloa d d ition of 16 w ith 7a in Ben zen e. A
solution of 16 (100 mg, 0.68 mmol), 7a (132 mg, 1.36 mmol),
and Mn(OAc)3 (636 mg, 2.72 mmol) in 10 mL of benzene was
refluxed at 80 °C for 3 d. Normal workup and flash chroma-
tography on silica gel (50:1 hexane/EtOAc, then 15:1 hexane/
EtOAc) gave 74 mg (45%) of spiro[cyclohexane-1,2′(3′H)-
naphtho[1,2-b]furan] (17), followed by 29 mg (18%) of 18 and
26 mg (26%) of recovered 16.
The data for 17: 1H NMR 7.97 (m, 1), 7.77 (m, 1), 7.39 (m,
2), 7.32 (d, 1, J ) 8.2), 7.28 (d, 1, J ) 8.2), 3.12 (s, 2), 1.97-
1.48 (m, 10); 13C NMR 154.2, 133.9, 127.8, 125.3, 124.8, 123.3,
121.7, 120.8, 119.3, 119.2, 89.3, 41.9, 37.4, 25.3, 23.0; IR (neat)
3056, 1944, 1814, 1684, 1581, 1516, 1445, 1378.
The data for 12ba : 1H NMR 5.85 (br dd, 1, J ) 2.7, 1.3),
5.42 (br s, 1), 2.54 (br d, 1, J ) 14.9), 2.38-2.24 (m, 3), 2.09-
1.82 (m, 5), 1.95 (s, 3), 1.68-1.49 (m, 6); 13C NMR 201.7, 161.5,
135.2, 126.2, 123.4, 43.1, 37.7, 29.8, 27.8, 26.6, 25.3, 24.1, 22.9,
22.4; IR (neat) 1669, 1638, 1438, 1379, 1210.
The data for 18: 1H NMR 8.03 (d, 1, J ) 7.8), 7.46 (dd, 1, J
) 7.8, 7.6), 7.30 (dd, 1, J ) 7.6, 7.5), 7.24 (d, 1, J ) 7.5), 5.47
(s, 1), 3.00-2.93 (m, 2), 2.72-2.58 (m, 2), 2.22-1.47 (m, 11);
13C NMR 200.4, 144.1, 135.1, 133.1, 132.5, 128.7, 127.5, 126.5,
123.7, 45.2, 38.0, 28.1, 27.9, 27.4, 25.3, 23.0, 22.5; IR (neat)
1682, 1600, 741.
Oxid a tive Cycloa d d ition of 1a w ith â-Meth ylstyr en e
(19a ) in Ben zen e. A solution of 1a (105 mg, 1.10 mmol), 19a
(143 mg, 1.21 mmol), and Mn(OAc)3 (1.02 g, 4.40 mmol) in 10
mL of benzene was refluxed at 80 °C for 3 d. Normal workup
and flash chromatography on silica gel (50:1 hexane/EtOAc,
then 15:1 hexane/EtOAc) gave 69 mg (42%) of unreacted 19a ,
followed by 46 mg (18%) of a 93:7 mixture of trans-2,3-dihydro-
3-methyl-2-phenylbenzofuran (20a a ) and the cis isomer, and
2% of cinnamyl acetate.
The data for 15ba : 1H NMR 7.00 (d, 1, J ) 7.5), 6.61 (d, 1,
J ) 7.5), 6.58 (s, 1), 2.92 (s, 2), 2.29 (s, 3), 1.80-1.47 (m, 10);
13C NMR 159.0, 137.9, 124.7, 123.8, 120.4, 110.2, 88.6, 40.7,
37.2, 25.2, 23.1, 21.5; IR (neat) 1622, 1590, 1499, 1448, 1275,
1250, 1032, 946, 796.
Oxid a tive Cycloa d d ition of 3-Eth oxy-2-cycloh exen on e
(1c) w ith 7b in Ben zen e. A solution of 1c (115 mg, 0.82
mmol), 7a (158 mg, 1.64 mmol), and Mn(OAc)3 (762 mg, 3.38
mmol) in 10 mL of benzene was refluxed at 80 °C for 3 d.
Normal workup and flash chromatography on silica gel (50:1
hexane/EtOAc, 15:1 hexane/EtOAc, then 1:1 hexane/EtOAc)
gave 74 mg (39%) of 6-ethoxyspiro[benzofuran-2(3H),1′-cyclo-
hexane] (15ca ), followed by 4 mg (2%) of 6-(1-cyclohexenyl-
methyl)-3-ethoxy-2-cyclohexenone (12ca ), and 50 mg (43%) of
recovered 1c.
The data for 20a a : 1H NMR 7.45-7.30 (m, 5), 7.19 (br d, 1,
J ) 7.4), 7.15 (br dd, 1, J ) 8.0, 7.4), 6.92 (br dd, 1, J ) 7.4,
7.4), 6.87 (br d, 1, J ) 8.0), 5.16 (d, 1, J ) 8.7), 3.44 (dq, 1, J
) 8.7, 6.8), 1.43 (d, 3, J ) 6.8); 13C NMR 159.2, 140.9, 131.9,
128.6 (2 C), 128.24, 128.18, 126.0 (2 C), 123.6, 120.8, 109.5,
92.4, 45.6, 18.1; IR (neat) 1597, 1478, 1432, 750.
The data for 12ca : 1H NMR 7.54 (d, 1, J ) 8.6), 6.60 (dd, 1,
J ) 2.2, 8.6), 6.51 (d, 1, J ) 2.2), 4.10 (q, 2, J ) 7.0), 1.81-
1.55 (m, 10), 1.45 (t, 3, J ) 7.0); 13C NMR 201.8, 173.6, 167.6,
125.7, 113.0, 111.8, 96.6, 90.6, 64.2, 31.7, 24.6, 21.7, 14.5; IR
(neat) 1709, 1613, 1447, 1292, 1179, 1097.
Partial data for the cis isomer: 1H NMR 5.81 (d, 1, J ) 8.8),
3.70 (m, 1), 0.81 (d, 3, J ) 7.2).
Oxid a tive Cycloa d d ition of 1a w ith An eth ole (19b) in
Ben zen e. A solution of 1a (96 mg, 1.00 mmol), anethole (150
mg, 1.01 mmol), Mn(OAc)3 (928 mg, 4.00 mmol), and 8 mL of
benzene was stirred in a sealed tube at 140 °C for 2 d. Normal
workup and flash chromatography on silica gel (50:1 hexane/
EtOAc, then 10:1 hexane/EtOAc) gave 55 mg (37%) of recov-
ered trans-anethole, followed by 73 mg (31%) of a 50:1 mixture
of trans-2,3-dihydro-2-(4-methoxyphenyl)-3-methylbenzofuran
(20a b ) and the cis isomer, and 8 mg (4%) of 3-(4-methoxy-
phenyl)-2(E)-propenyl acetate.
The data for 15ca : 1H NMR 6.97 (br d, 1, J ) 8.5), 6.35
(dd, 1, J ) 8.5, 2.0), 6.34 (d, 1, J ) 2), 3.97 (q, 2, J ) 7.0), 2.89
(s, 2), 1.86-1.45 (m, 10), 1.37 (t, 3, J ) 7.0); 13C NMR 160.3,
160.0, 125.4, 118.9, 106.4, 97.0, 89.8, 63.9, 40.7, 37.5, 25.5, 23.4,
15.2; IR (neat) 1621, 1495, 1446, 1294, 1168, 1038, 969, 926.
Oxid a tive Cycloa d d ition of Eth yl 2-Meth yl-4-oxo-2-
cycloh exen eca r boxyla te (1d ) w ith 7a in Ben zen e.
A
solution of 1d (121 mg, 0.66 mmol), 7a (128 mg, 1.33 mmol),
and Mn(OAc)3 (617 mg, 2.66 mmol) in 10 mL of benzene was
refluxed at 80 °C for 3 d. Normal workup and flash chroma-
tography on silica gel (25:1 hexane/EtOAc, then 3:1 hexane/
EtOAc) gave 34 mg (25%) of ethyl 6-methylspiro[benzofuran-
2(3H),1′-cyclohexane]-5-carboxylate (15d a ), followed by 62 mg
(51%) of recovered 1c.
The data for 20a b: 1H NMR 7.35 (d, 2, J ) 8.7), 7.16 (dd,
1, J ) 6.9, 6.1), 7.13 (d, 1, J ) 6.9), 6.90 (d, 2, J ) 8.7), 6.88-
6.94 (m, 1), 6.84 (d, 1, J ) 8.3), 5.09 (d, 1, J ) 8.9), 3.79 (s, 3),
3.43 (dq, 1, J ) 8.9, 6.8), 1.39 (d, 3, J ) 6.8); 13C NMR 160.0,
159.5, 133.1, 132.4, 128.6, 128.0, 124.0, 121.0, 114.4, 109.8,
92.7, 55.7, 45.7, 18.2; IR (neat) 1614, 1514, 1478, 1376, 1249.
Partial data for the cis isomer: 1H NMR 5.75 (d, 1, J ) 8.7),
0.82 (d, 3, J ) 8.3).
P r ep a r a t ion of 4-(3-Ch lor op r op yl)-2-cycloh exen on e
(1g).15 To a solution of diisopropylamine (0.9 mL, 7.00 mmol)
in 5 mL of dry THF at 0 °C under N2 was added n-butyllithium
solution (2.5 M in hexane, 2.5 mL, 6.25 mmol). After 15 min
at 0 °C, the solution was cooled to -78 °C, and 3-ethoxy-2-
cyclohexenone (712 mg, 5.08 mmol) in 2.5 mL of THF was
added dropwise over 30 min. The solution was warmed to -40
°C, and HMPA (1.25 g, 6.98 mmol) in THF and then 1-chloro-
3-iodopropane (1.43 g, 7.01 mmol) were added. The mixture
was warmed to rt over 1.5 h and then stirred at rt for
additional 2 h. Saturated NH4Cl solution was added, and the
mixture was extracted with hexane (2 × 10 mL). The
combined organic layers were washed with saturated NaCl
solution, dried (Na2SO4), and concentrated to provide 1.3 g of
crude product.
The data for 15d a : 1H NMR 7.77 (s, 1), 6.59 (s, 1), 4.30 (q,
2, J ) 7.1), 2.93 (s, 2), 2.56 (s, 3), 1.85-1.70 (m, 4), 1.70-1.60
(m, 2), 1.60-1.45 (m, 4), 1.37 (t, 3, J ) 7.1); 13C NMR 167.4,
162.1, 142.4, 128.0, 124.4, 121.2, 112.4, 90.2, 60.1, 40.3, 37.1,
25.1, 23.0, 22.5, 14.4; IR (neat) 1712, 1621, 1583, 1494, 1257.
Oxid a tive Cycloa d d ition 5-Meth yl-2-cycloh exen on e
(1e) w ith 7a in Ben zen e. A solution of 1e (92 mg, 0.84
mmol), 7a (160 mg, 1.66 mmol), and Mn(OAc)3 (770 mg, 3.32
mmol) in 10 mL of benzene was refluxed at 80 °C for 3 d.
Normal workup and flash chromatography on silica gel (50:1
hexane/EtOAc, then 15:1 hexane/EtOAc) gave 70 mg (41%) of
15ea , followed by 18 mg (9%) of 6-(1-cyclohexenylmethyl)-5-
methyl-2-cyclohexenone (12ea ) as a 3:2 trans/cis mixture and
3 mg (3%) of recovered 1e.
The data for 12ea : 1H NMR 6.80 (m,1), 5.96 (br d, J ) 10.0),
5.46 (br s, 0.6 × 1), 5.41 (br s, 0.4 × 1), 2.60-1.80 (m, 10),
1.70-1.50 (m, 4), 1.05 (d, 0.6 × 3, J ) 6.9), 0.92 (d, 0.4 × 3, J
) 6.9); 13C NMR (202.1, 202.0), (147.3, 146.9), (135.1, 134.9),
(129.2, 128.4), (123.7, 123.3), (51.4, 49.5), (38.1, 37.3), (33.7,
33.3), (31.5, 31.1), (27.97, 27.90), (25.3, 25.3), (22.92, 22.88),
(22.43, 22.37), (19.8, 14.2).
The above product in 10 mL of dry THF was added dropwise
to lithium aluminum hydride solution (1.0 M in THF, 4.6 mL,
4.60 mmol) under N2 at 0 °C. The mixture was warmed to rt
and then held at rt for 1 h. Water (0.1 mL, then 5 mL) and
then 2 N HCl solution (to adjust the pH to 2) were added. After
The data for 15ea : 1H NMR 7.00 (dd, 1, J ) 7.6. 7.6), 6.62
(d, 1, J ) 7.6), 6.58 (d, 1, J ) 7.6), 2.87 (s, 2), 2.21 (s, 3), 1.86-