1H), 2.85 (t, J ) 7.2 Hz, 2H), 3.69 (dd, J ) 1.8, 18 Hz, 1H), 3.79
(s, 3H), 4.00 (br s, 1H), 5.08-5.23 (m, 2H), 5.62 (br s, 1H), 5.81-
5.91 (m, 1H); 13C NMR δ 32.6, 37.1, 53.0, 55.2, 80.3, 117.9, 125.2,
125.7, 126.6, 134.1, 142.9, 156.2. Anal. Calcd for C13H15NO2S:
C, 62.63; H, 6.06; N, 5.62. Found: C, 62.91; H, 6.25; N, 6.14.
P h en yl N-(1-Cycloh exyl-3-bu ten yl)-N-(2-p r op yn yl)ca r -
ba m a te 5c: yellow oil (68%); 1H NMR δ 0.93-2.12 (m, 11H),
2.13-2.31 (m, 2H), 2.47-2.52 (m, 1H), 3.86-4.09 (m, 3H), 5.03-
5.15 (m, 2H), 5.79-5.86 (m, 1H), 7.07-7.39 (m,5H); 13C NMR
(rotamers present) δ 25.7, 26.0, 26.2, 30.3, 34.1, 34.4, 39.9, 40.4,
62.1, 71.2, 80.01, 117.2, 120.8, 125.2, 126.2, 129.4, 135.4, 151.4.
Anal. Calcd for C20H25NO2: C, 77.13; H, 8.09; N, 4.50. Found:
C, 77.65; H, 8.15; N, 4.84.
Meth yl N-(2-Bu tyn yl)-N-[1-(2-fu r yl)-3-bu ten yl]-ca r ba m -
a te 5d : yellow oil (61%); 1H NMR δ 1.73 (s, 3H), 2.77 (t, J )
7.28 Hz, 1H), 3.65 (br d, 1H), 3.76 (s, 3H), 3.89-4.00 (m, 1H),
5.10 (dd, J ) 17.0, 14.8 Hz, 2H), 5.79 (m, 1H), 6.28-6.32 (m,
2H), 7.36(s, 1H); 13C NMR δ 3.4, 31.2, 36.1, 39.0, 40.0, 54.1, 76.6,
78.9, 106.8, 109.7, 117.7, 134.6, 141.6, 155.2. Anal. Calcd for
C14H17NO3: C, 68.00; H, 6.93; N, 5.66. Found: C, 68.23; H, 7.21;
N, 6.00.
(t, J ) 14.4 Hz, 1H), 5.45-5.60 (m, 1H), 5.85 (br s, 1H), 6.75 (br
s, 1H), 6.90 (br s, 1H),7.15 (br s, 1H); 13C NMR δ 24.1, 30.2,
30.9, 40.6, 43.5, 45.2, 51.9, 53.0, 121.7, 123.6, 123.9, 127.1, 156.2,-
173.7, 171.6. Anal. Calcd for C22H19NO5: C, 64.53; H, 4.68; N,
3.42. Found: C, 64.77; H, 4.54; N, 3.12.
Meth yl 8-(2-F u r yl)-4-m eth yl-1,3-d ioxo-3,3a ,4,6,8,9,9a ,9b-
oct a h yd r ofu r o[3,4-f]isoq u in olin e-7(1H )-ca r b oxyla t e 7c:
white powder (58%), mp 165-167 °C; 1H NMR (at 60 °C) δ 1.80
(s, 3H), 2.17 (s, 3H), 2.21 (br d, J ) 15.5 Hz, 1H), 2.29-2.37 (m,
2H), 2.57 (dd, J ) 15.5, 2.1 Hz, 1), 2.68 (ddd, J ) 15.5, 4.6 Hz,
1H), 3.92 (app heptd, 1H), 3.23 (dd, J ) 9.5, 5.9 Hz, 1H), 3.33
(ddd, J ) 9.5, 6.9 Hz, 1H), 4.41 (d, J ) 15.8 Hz, 1H), 5.39 (app
t, 1H), 5.99 (dt, J ) 3.24, 0.9 Hz, 1H), 6.26 (ddd, J ) 3.24, 1.85
Hz, 1H), 7.29 (ddd, J ) 1.85, 0.9 Hz, 1H); 13C NMR (at 60 °C) δ
18.8, 28.7, 30.9, 31.7, 41.0, 41.4, 44.1, 49.5, 52.7, 106.1, 110.2,
128.0, 129.3, 141.6, 154.5, 171.5,173.5. Anal. Calcd for C18H19
-
NO6: C, 62.60; H, 5.55; N, 4.06. Found: C, 62.11; H, 5.92; N,
3.98.
P h e n yl
4-Me t h yl-8-(5-m e t h yl-2-fu r yl)-1,3-d ioxo-3,-
3a ,4,6,8,9,9a ,9b -oct a h yd r ofu r o[3,4-f]isoq u in olin e-7(1H )-
ca r boxyla te 7d : yellow oil (73%); 1H NMR δ 1.82 (s, 3H), 2.26
(s, 3H), 2.28 (s, 1H), 2.36-2.39 (m, 2H), 2.71-2.88 (m, 1H), 3.30-
3.38 (m, 2H), 3.90 (d, J ) 14.8 Hz, 0.6 H), 4.12 (d, J ) 14.8 Hz,
0.4 H), 4.62 (d, J ) 15.8 Hz, 1H), 5.50 (br. s, 1H), 5.88-5.96 (m,
2H), 7.00 (d, J ) 7.5 Hz, 1H), 7.10-7.19 (m, 2H), 7.26-7.34 (m,
2H); 13C NMR δ 13.6, 19.1, 27.9, 30.8, 31.5, 40.9, 41.1, 44.0, 50.4,
76.5, 106.1, 106.8, 121.6, 121.7, 125.3, 127.6, 129.2, 129.9, 151.3,
152.1, 151.1,171.8. Anal. Calcd for C24H23NO6: C, 68.40; H, 5.50;
N, 3.32. Found: C, 68.48; H, 5.18; N, 2.74.
P h en yl N-(2-Bu tyn yl)-N-[1-(5-m eth yl-2-fu r yl)-3-bu ten yl]-
1
ca r ba m a te 5e: yellow oil (68%); H NMR δ 1.76 (s, 3 H), 2.28
(s, 3H), 2.72 (br s, 2H), 3.75-3.83 (m, 1H), 4.09 (dd, J ) 2.06,
17.8 Hz, 1H), 5.08-5.22 (m, 2H), 5.41 (t, J ) 7.2 Hz, 1H), 5.92
(br s, 2H), 6.21 (d, J ) 2.9 Hz, 1H), 7.12-7.22 (m, 3H),7.35 (t, J
) 7.7 Hz, 2H); 13C NMR δ 3.5, 13.5, 14.1, 33.1, 35.0, 41.7, 42.1,
105.9, 109.4, 117.5, 121.6, 124.8, 125.1, 129.0, 134.2, 150.3, 151.9,
154.01. Anal. Calcd for C20H21NO3: C, 74.28; H, 6.55; N, 4.33.
Found: C, 74.45; H, 6.51; N, 4.58.
P h en yl 8-Cycloh exyl-1,3-d ioxo-3,3a ,4,6,8,9,9a ,9b-octa h y-
d r ofu r o[3,4-f]isoqu in olin e-7(1H)-ca r boxyla te 7e: colorless
oil (68%); 1H NMR δ 1.02-1.26 (m, 5H), 1.60-1.82 (m, 4H),
2.17-2.20 (m, 4H), 2.28-2.33 (m, 1H), 2.71-2.85 (m, 2H), 3.41-
3.43 (m, 2H), 3.74 (d, J ) 16.4 Hz, 0.5 H), 4.01 (d, J ) 16.4 Hz,
0.5 H), 4.14-4.23 (m, 1H), 4.45 (d, J ) 15.6 Hz, 1H), 5.84 (br s,
1H), 7.08 (d, J ) 7.6 Hz, 1H), 7.21 (t, J ) 7.4 Hz, 2H), 7.35 (t, J
) 7.5 Hz, 2H); 13C NMR δ 22.9, 26.0, 26.0, 29.7, 29.9, 37.2, 37.2,
39.9, 40.3, 43.2, 43.5, 45.0, 56.2, 120.5, 121.7, 125.2, 125.3, 129.1,
129.2, 134.8, 151.3,171.2. Anal. Calcd For C24H27NO5: C, 70.40;
H, 6.65; N, 3.42. Found: C, 70.00; H, 6.89; N, 3.29.
8-Meth yl-3-p h en yl-3,4,4a ,7-tetr a h yd r o-1H-isoqu in olin e-
2,5,6-tr ica r boxylica cid -tr im eth yl Ester 7f: colorless liquid
(72%); 1H NMR δ (at 60 °C) 1.76 (s, 3H), 1.80 (d, J ) 5.4, 0.5
Hz, 0.5H), 1.85 (d, J ) 5.4 Hz, 0.5 H), 2.64 (d, J ) 13.3 Hz, 1H),
2.79 (d, J ) 6.9 Hz, 0.5 H), 2.86 (d, J ) 6.4 Hz, 0.5 H), 2.99 (d,
J ) 7.2 Hz, 0.5 H), 3.07 (d, J ) 7.2 Hz, 0.5 H), 3.15 (d, J ) 14.4
Hz, 1H), 3.74 (s, 3H), 3.24 (br s, 1H), 3.78 (s, 3H), 3.75 (s, 3H),
4.95 (d, J ) 14.4 Hz, 1H), 5.57 (br s, 1H), 7.20-7.38 (m, 5 H);
13C NMR δ (at 60 °C) 17.4, 33.7, 35.2, 41.6, 51.7, 51.8, 52.6, 53.9,
122.4, 124.9, 126.4, 126.9, 128.4, 128.7, 131.8, 135.9, 138.8, 156.3,
167.5, 167.7. Anal. Calcd for C22H25NO6: C, 66.15; H, 6.31; N,
3.51. Found: C, 66.10; H, 6.32; N, 3.28.
Rin g-Closin g Metath esis/Diels-Alder Reaction of En yn es
5a -e. To a solution of Grubbs catalyst (5 mol %) in CH2Cl2 (40
mL) was added enyne 5 (10 mmol), and the mixture was reflux
under argon for 12 h. Methylene chloride was removed in vacuo,
and the crude diene (in the cases of 6a and 6b) was refluxed
with the respective dienophile (20 mmol) in toluene (25 mL) for
15 h. Other piperidine carbamates 6c-e (10 mmol scale) were
purified over silica gel and subsequently refluxed in toluene (25
mL) with the appropriate dienophile (20 mmol) for 15 h. After
concentration, the residue was taken in ethyl acetate. The
organic layer was washed with water and brine and dried over
sodium sulfate. After concentration, the crude product was
purified by column chromatography over silica gel (200-400
mesh) using hexane/EtOAc (70%) as the eluent. NMR spectra
of 6a -f and 7a -f were recorded at room temperature, and
rotamers were present.
P h en yl 1,3-Dioxo-8-p h en yl-3,3a ,4,6,8,9,9a ,9b-octa h yd r o-
fu r o[3,4-f]isoqu in olin e-7(1H)-car boxylate 7a: brown oil (87%);
1H NMR δ 1.90-2.16 (m, 3H), 2.64 (dd, J ) 7.2, 8.4 Hz, 1H),
2.82-2.96 (m, 1H), 3.08 (dd, J ) 6, 9.3 Hz, 1H), 3.20 (t, J ) 8.7
Hz, 1H), 3.93 (d, J ) 15.3, 0.63H), 4.13 (d, J ) 14.4 Hz, 0.36H),
4.56-4.65 (m, 1H), 5.38-5.48 (br m, 1H), 5.94 (br s, 1H); 13C
NMR δ 24.2, 29.7, 29.8, 29.9, 30.0, 40.6, 43.4, 45.1, 45.7, 55.8,
56.0, 121.4, 122.0, 125.2, 126.9, 128.4, 128.9, 129.0, 137.1, 141.0,
141.9, 150.8, 154.0, 171.7, 173.8. Anal. Calcd for C24H21NO5: C,
71.45; H, 5.25; N, 3.47. Found: C, 71.67; H, 5.54; N, 3.12.
Meth yl 1,3-Dioxo-8-(2-th ien yl)-3,3a ,4,6,8,9,9a ,9b-octa h y-
d r ofu r o[3,4-f]isoqu in olin e-7(1H)-ca r boxyla te 7b: yellow oil
(82%); 1H NMR δ 2.05-2.34 (m, 3), 2.61-2.75 (m, 2H), 3.22-
3.33 (m, 2H), 3.57-3.65 (m, 2H), 3.91 (d, J ) 15.3 Hz, 1H), 4.23
Su p p or tin g In for m a tion Ava ila ble: Spectral data of 5f,g
and 6a -f, 1H NMR spectra of 6a and 6b, and NOESY
spectrum of 7c. This material is available free of charge via
the Internet at http://pubs.acs.org.
J O0340408
J . Org. Chem, Vol. 68, No. 14, 2003 5727