Occhiato et al.
H), 2.61 (m, 1 H), 2.00 (d, J ) 19.0 Hz, 1 H), 1.96 (m, 1 H),
1.56 (m, 1 H), 1.14 (d, J ) 6.2 Hz, 3 H), 1.11 (d, J ) 6.2 Hz, 3
H). 13C NMR (50.33 MHz, CDCl3, δ): 191.1 (s), 164.6 (s), 153.9
(s), 137.0 (s), 136.1 (s), 128.3 (d, 2 C), 128.0 (d, 2 C), 127.9 (d),
68.0 (t), 42.8 (t), 42.6 (t), 31.0 (t), 30.8 (d), 28.4 (d), 18.8 (q),
H). 13C NMR (50.33 MHz, CDCl3, δ): 154.0 (s), 153.3 (s), 133.7
(d), 128.5 (d), 112.9 (t), 106.1 (d), 65.9 (t), 63.7 (t), 38.0 (t), 31.9
(d), 30.2 (t), 29.8 (t), 15.4 (q), 14.8 (q). MS m/z: 222 (M+, 100),
111 (64). Anal. Calcd for C14H22O2: C, 75.63; H, 9.97. Found:
C, 75.49; H, 10.36.
18.0 (q). MS m/z: 299 (M+, 6), 240 (100). Anal. Calcd for C18H21
-
4-Eth yl-6-m eth yl-2,3,4,5,6,7-h exa h yd r o-cyclop en ta [b]-
oxep in -8-on e (75). This was obtained as a 3:1 diastereomeric
mixture using the procedure described for 19 starting from
74 (84 mg, 0.38 mmol). Purification by flash chromatography
(Et2O-petroleum ether, 1:1, Et3N 0.5%) gave 75 (48 mg, 65%,
Rf ) 0.38) as a white oil and 76 (7 mg, 9%, Rf ) 0.54).
NO3: C, 72.22; H, 7.07; N, 4.68. Found: C, 72.17; H, 7.33; N,
4.87.
1
70. H NMR (200 MHz, CDCl3, δ): 7.28 (m, 5 H), 6.80 (dq,
J ) 15.8, 6.6 Hz, 1 H), 6.19 (d, J ) 15.8 Hz, 1 H), 5.68 (d, J )
3.3 Hz, 1 H), 5.07 (s, 2 H), 3.80-3.50 (m, 2 H), 2.40 (m, 1 H),
1.91 (m, 1 H), 1.76 (d, J ) 6.6 Hz, 3 H), 1.49 (m, 1 H), 1.02 (d,
J ) 6.9 Hz, 3 H).
1
75. H NMR (400 MHz, CDCl3, δ) (major diastereoisomer):
4.32 (m, 1 H), 3.85 (m, 1 H), 2.75-2.60 (m, 2 H), 2.31 (m, 1
H), 2.22 (m, 1 H), 1.95 (dd, J ) 16.3, 1.8 Hz, 1 H), 1.70-1.55
(m, 2 H), 1.39 (m, 1 H), 1.28-1.15 (m, 2 H), 1.01 (d, J ) 6.95
Hz, 3 H), 0.90 (t, J ) 6.5 Hz, 3 H). 13C NMR (100.4 MHz,
CDCl3, δ) (major distereoisomer): 202.4 (s), 154.7 (s), 154.1
(s), 71.7 (t), 41.4 (t), 38.4 (t), 36.7 (d), 35.4 (d), 33.9 (t), 29.7 (t),
19.8 (q), 11.6 (q). MS m/z: 194 (M+, 100), 109 (45).
(4R*,5S*)-4,5-Dim eth yl-1-(tolu en e-4-su lfon yl)-1,2,3,4,5,6-
h exa h yd r o[1]p yr in d in -7-on e (67). The hydrolysis of 63 (50
mg, 0.14 mmol) was carried out as described above for the
synthesis of 46. After 24 h, chromatography (EtOAc-petro-
leum ether 1:4, 0.5% Et3N, Rf ) 0.23) gave the Nazarov product
67 (23 mg, 51%) as a white solid and dienone 71 (6 mg, 7%, Rf
) 0.39).
1
76. H NMR (400 MHz, CDCl3, δ): 6.97 (dqd, J ) 16.1, 6.5,
67. Mp 113-114 °C. 1H NMR (400 MHz, CDCl3, δ): 7.97
(d, J ) 8.4 Hz, 2 H), 7.28 (d, J ) 8.4 Hz, 2 H), 3.53 (m, 1 H),
3.29 (m, 1 H), 2.91 (m, 1 H), 2.74-2.53 (m, 2 H), 2.39 (s, 3 H),
2.13-1.96 (m, 2 H), 1.67 (m, 1 H), 1.15 (d, J ) 6.2 Hz, 3 H),
1.11 (d, J ) 6.9 Hz, 3 H). 13C NMR (50.33 MHz, CDCl3, δ):
190.0 (s), 166.2 (s), 143.4 (s), 138.2 (s), 136.2 (s), 129.3 (d, 2
C), 127.8 (d, 2 C), 44.7 (t), 42.2 (t), 31.3 (d), 30.6 (t), 28.1 (d),
21.5 (q), 19.0 (q), 17.8 (q). MS m/z: 319 (M+, 44), 91 (100).
Anal. Calcd for C17H21NO3S: C, 63.92; H, 6.63; N, 4.39.
Found: C, 63.81; H, 6.94; N, 4.12.
71. 1H NMR (200 MHz, CDCl3, δ): 7.71 (d, J ) 8.4 Hz, 2
H), 7.29 (d, J ) 8.4 Hz, 2 H), 6.99 (dq, J ) 15.7 Hz, 7.0 Hz, 1
H), 6.57 (d, J ) 15.7 Hz, 1 H), 5.91 (d, J ) 3.3 Hz, 1 H), 3.60-
3.32 (m, 2 H), 2.40 (s, 3 H), 2.21 (m, 1 H), 1.93 (d, J ) 7.0 Hz,
3 H), 1.47-1.36 (m, 2 H), 1.21 (d, J ) 8.8 Hz, 3 H).
6-Bu t-2-en oyl-4-ter t-bu tyl-3,4-d ih yd r o-2H-p yr id in e-1-
ca r boxylic Acid Ben zyl Ester (72). The hydrolysis of 64 (80
mg, 0.22 mmol) was carried out as described above. Chroma-
tography (EtOAc-petroleum ether 1:10, 0.5% Et3N, Rf ) 0.38)
gave dienone 72 (34 mg) in 45% yield as a yellowish oil. 1H
NMR (200 MHz, CDCl3, δ): 7.28 (m, 5 H), 6.80 (dq, J ) 15.4,
6.7 Hz, 1 H), 6.19 (d, J ) 15.4 Hz, 1 H), 5.83 (d, J ) 2.9 Hz, 1
H), 5.07 (s, 2 H), 4.15 (dt, J ) 12.8, 3.7 Hz, 1 H), 3.20 (td, J )
12.8, 2.9 Hz, 1 H), 2.10 (m, 1 H), 1.84 (m, 1 H), 1.78 (d, J )
6.7 Hz, 3 H), 1.60 (m, 1 H), 0.91 (s, 9 H). 13C NMR (CDCl3, δ):
197.9 (s), 155.9 (s), 143.4 (d), 139.9 (s), 135.7 (s), 128.5 (d),
128.3 (d, 2 C), 128.2 (d, 2 C), 128.1 (d), 123.1 (d), 67.8 (t), 44.7
(d), 44.3 (t), 33.2 (s), 27.3 (q, 3 C), 25.2 (t), 18.2 (q). MS m/z:
341 (M+, 2), 91 (100). Anal. Calcd for C21H27NO3: C, 73.87; H,
7.97; N, 4.10. Found: C, 73.65; H, 8.12; N, 4.43.
1.8 Hz, 1 H), 6.72 (dd, J ) 15.9, 1.8 Hz, 1 H), 6.25 (ddd, J )
10.2, 4.8, 1.8 Hz, 1 H), 4.25 (m, 1 H), 3.81 (m, 1 H), 2.14-2.03
(m, 2 H), 1.89 (d, J ) 6.5 Hz, 1 H), 1.38-1.30 (m, 5 H), 0.90 (t,
J ) 6.5 Hz, 3 H). 13C NMR (100.4 MHz, CDCl3, δ): 187.6 (s),
157.3 (s), 144.2 (d), 128.5 (d), 119.1 (t), 71.5 (t), 37.5 (t), 37.1
(d), 31.6 (q), 29.0 (t), 18.6 (t), 11.3 (q). MS m/z: 194 (M+, 18),
69 (100).
(E)-6-(1-Eth oxy-2-m eth yl-bu ta -1,3-d ien yl)-3,4-d ih yd r o-
2H-p yr a n (77). This compound was prepared as described for
18 starting from 16 (166 mg, 0.5 mmol) and dienylboronate
12c (112 mg, 0.5 mmol). After purification by flash chroma-
tography (Et2O-petroleum ether 1: 9, 0.5% Et3N, Rf ) 0.86)
pure 77 (62 mg, 64% yield) was obtained as a pale yellow oil.
1H NMR (400 MHz, CDCl3, δ): 6.80 (dd, J ) 15.7, 10.8 Hz, 1
H), 5.03 (dd, J ) 15.7, 1.8 Hz, 1 H), 4.95-4.85 (m, 2 H), 4.05
(t, J ) 6.1 Hz, 2 H), 3.78 (q, J ) 7.3 Hz, 2 H), 2.14 (m, 2 H),
1.87-1.84 (m, 2 H), 1.81 (s, 3 H), 1.23 (t, J ) 7.3 Hz, 3 H). 13
C
NMR (100.4 MHz, CDCl3, δ): 150.1 (s), 146.3 (s), 136.2 (s),
119.1 (d), 110.6 (t), 106.3 (d), 66.1 (t), 64.6 (t), 22.3 (t), 21.7 (t),
15.5 (q), 10.7 (q). MS m/z: 194 (M+, 100), 107 (100). Anal. Calcd
for C12H18O2: C, 74.19; H, 9.34. Found: C, 74.33; H, 9.09.
(5S*,6R*)-5,6-Dim eth yl-3,4,5,6-tetr ah ydr o-2H-cyclopen t-
a [b]p yr a n -7-on e (78). This compound was obtained as de-
scribed for 19 starting from 77 (63 mg, 0.32 mmol). Purification
by flash chromatography (Et2O-petroleum ether 1:1, 0.5%
Et3N) gave pure 78 (25 mg, 45%, Rf ) 0.38) as a white oil and
79 (13 mg, 21%, Rf ) 0.42).
1
78. H NMR (400 MHz, CDCl3, δ): 4.15 (m, 1 H), 4.03 (m,
1 H), 2.82 (pent, J ) 6.2 Hz, 1 H), 2.50 (pent, J ) 6.2 Hz, 1
H), 2.38 (dt, J ) 18.0, 5.6 Hz, 1 H), 2.22 (dt, J ) 18.0, 5.9 Hz,
1 H), 2.00-1.94 (m, 2 H), 1.08 (d, J ) 7.0 Hz, 3 H), 1.04 (d, J
) 7.0 Hz, 3 H). 13C NMR (100.4 MHz, CDCl3, δ): 203.3 (s),
166.8 (s), 149.8 (s), 66.9 (t), 42.2 (d), 36.1 (t), 22.0 (d), 21.7 (t),
14.9 (q), 11.3 (q). MS m/z: 166 (M+, 55), 151 (100). Anal. Calcd
for C10H14O2: C, 72.26; H, 8.49. Found: C, 72.51; H, 8.45.
79. 1H NMR (400 MHz, CDCl3, δ): 4.12-4.06 (m, 2 H), 2.38
(dt, J ) 18.0, 5.9 Hz, 1 H), 2.26 (qd, J ) 7.0, 1.8 Hz, 1 H), 2.21
(dt, J ) 18.0, 5.9 Hz, 1 H), 1.98-1.94 (m, 2 H), 1.94 (qd, J )
7.0, 1.8 Hz, 1 H), 1.19 (d, J ) 7.0 Hz, 3 H), 1.18 (d, J ) 7.0 Hz,
3 H) 13C NMR (100.4 MHz, CDCl3, δ): 202.2 (s), 165.8 (s), 147.8
(s), 67.6 (t), 41.8 (d), 37.7 (t), 23.2 (d), 21.4 (t), 15.5 (q), 12.8
(q). MS m/z: 166 (M+, 57), 151(100). Anal. Calcd for
P h osp h or ic Acid 5-Eth yl-4,5,6,7-tetr a h yd r o-oxep in -2-
yl Ester Dip h en yl Ester (73). This compound was prepared
as described for 16 starting from 5-ethyl-oxepan-2-one (710
mg, 5 mmol). After chromatography (Et2O-petroleum ether
1:1, 0.5% Et3N, Rf ) 0.53) phosphate 73 (1.27 g, 68%) was
1
obtained as a pale yellow oil. H NMR (200 MHz, CDCl3, δ):
7.40-7.10 (m, 10 H), 4.70 (m, 1 H), 4.30-3.85 (m, 2 H), 2.10-
1.80 (m, 3 H), 1.45 (m, 1H), 1.35-1.20 (m, 3 H), 0.92 (t, J )
7.1 Hz, 3 H). 13C NMR (50.33 MHz, CDCl3, δ): 172.3 (s), 157.7
(s, 2 C), 129.6 (d, 4 C), 121.3 (d, 2 C), 116.3 (d, 4 C), 89.9 (d),
65.7 (t), 37.9 (t), 33.5 (d), 27.6 (t), 23.5 (t), 11.9 (q).
(E)-7-(1-Eth oxybu ta -1,3-d ien yl)-4-eth yl-2,3,4,5-tetr a h y-
d r o-oxep in e (74). This compound was prepared as described
for 18 starting from 73 (190 mg, 0.5 mmol) and R-ethoxydi-
enylboronate 12a (105 mg, 0.5 mmol). After purification by
flash chromatography (Et2O-petroleum ether, 1:9, 0.5% Et3N,
Rf ) 0.78) pure 74 (84 mg, 76%) was obtained as a pale yellow
oil. 1H NMR (200 MHz, CDCl3, δ): 6.81 (dt, J ) 16.0, 10.0 Hz,
1 H), 5.43 (m, 1 H), 5.22 (d, J ) 10.0 Hz, 1 H), 5.02 (dd, J )
16.0, 1.0 Hz, 1 H), 4.83 (dd, J ) 10.0, 1.0 Hz, 1 H), 3.90-3.75
(m, 2 H), 3.47 (q, J ) 7.3 Hz, 2 H), 1.70-1.50 (m, 2 H), 1.40-
1.25 (m, 5 H), 1.20 (t, J ) 7.3 Hz, 3 H), 0.92 (t, J ) 7.1 Hz, 3
C
10H14O2: C, 72.26; H, 8.49. Found: C, 72.43; H, 8.46.
6-(1-Eth oxyh exa -1,3-d ien yl)-3,4-d ih yd r o-2H-p yr id in e-
1-ca r boxylic Acid Ben zyl Ester (82). This compound was
prepared as described for 18 starting from 6-trifluoromethane-
sulfonyloxy-3,4-dihydro-2H-pyridine-1-carboxylic acid benzyl
ester9a (182 mg, 0.5 mmol) and 12d (112 mg, 0.5 mmol). After
purification by flash chromatography (Et2O-petroleum ether
1:9, 0.5% Et3N, Rf ) 0.86) pure 82 (133 mg, 78%) was obtained
1
as a pale yellow oil. H NMR (200 MHz, CDCl3, δ): 7.25 (s, 5
H), 6.11 (m, 1 H), 5.45 (d, J ) 10.8 Hz, 1 H), 5.31 (t, J ) 4.5
9740 J . Org. Chem., Vol. 68, No. 25, 2003