The Journal of Organic Chemistry
Article
8.34 (d, J = 9.4, 2H), 7.94 (d, J = 9.4, 2H), 7.43 (m, 1H), 5.27 (s, 2H).
Salt obtained as a yellow solid, mp 138−139 °C.
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-(4-
hexylphenyl)cyclopent-2-enecarboxylate-11f. 85% yield (85
mg): H NMR CD3OD, 250 MHz, δ (ppm) 7.09 (s, 4H), 5.97 (dd,
1
1
4-Cyano-bezenediazonium tetrafluoroborate-10n. H NMR
J = 1.9 and 5.4, 1H), 5.82 (dd, J = 2.0 and 5.2, 1H), 4.04 (tt, J = 2.0
and 7.4, 1H), 3.71 (s, 3H), 3.29 (peak underneath residual CD3OD,
1H), 2.56 (t, J = 7.3, 2H), 1.78 (dd, J = 7.5 and 13.6, 1H), 1.58 (qn, J =
7.7, 2H), 1.41 (s, 9H), 1.30 (m, 6H), 0.88 (t, J = 6.7, 3H); 13C NMR
CD3OD, 62.5 MHz, δ (ppm) 175.6, 157.6, 143.0, 142.4, 141.0, 132.1,
129.8, 128.4, 80.7, 72.4, 53.1, 51.9, 47.6, 36.7, 33.0, 32.9, 30.2, 28.9,
23.2, 14.6; HRMS calcd for (C24H35NO4H) 402.2644, found
402.2674.
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-(4-
heptylphenyl)cyclopent-2-enecarboxylate-11g. 78% yield (81
mg): 1H NMR CD3OD, 250 MHz, δ (ppm) 7.09 (s, 4H), 5.98 (dd, J =
2.0 and 5.4, 1H), 5.82 (bs, 1H), 4.04 (m, 1H), 3.72 (s, 3H), 3.30 (peak
underneath residual CD3OD, 1H), 2.55 (t, J = 7.5, 2H), 1.78 (dd, J =
7.6 and 13.7, 1H), 1.42 (s, 9H), 1.57 (m, 2H), 1.30 (m, 8H), 0.89 (m,
3H); 13C NMR CD3OD, 62.5 MHz, δ (ppm) 175.5, 157.5, 142.9,
142.5, 141.0, 132.1, 129.8, 128.4, 80.6, 72.3, 53.1, 51.9, 47.6, 36.7, 33.1,
32.9, 30.4, 30.4, 28.9, 23.8, 14.6; HRMS calcd for (C25H37NO4H)
416.2797, found 416.2801.
acetone-d6, 250 MHz, δ (ppm) 9.07 (d, J = 10, 2H), 8.51 (d, J = 10,
2H). (ArNN) 2297. Salt obtained as a yellow solid, mp 119−120
°C.
General Procedure for the Heck−Matsuda Reaction. To a
round-bottomed flask (or a test tube) were added Pd2(dba)3 (4 mol %,
9.2 mg), sodium acetate (3 equiv, 0.062 g) and benzonitrile (2.5 mL).
To the resulting suspension was then added the olefin 6a,b (1.2 equiv,
0.3 mmol) followed by addition of the arenediazonium tetrafluor-
oborate 11a−n (0.25 mmol). The reaction was stirred at room
temperature with the reaction progress monitored by the evolution of
N2. After nitrogen ceased bubbling, the reaction mixture was loaded
directly onto a silica gel column and flash chromatographed using
hexanes/ethyl acetate (9:1) as eluent to give the desired Heck adducts
as homogeneous materials (single spot on TLC). Except when noted,
the products were obtained as clean pale yellow oils. Note: The
physical conditions of the base NaOAc is crucial to attain good yields
in the Heck−Matsuda reactions. The NaOAc has limited solubility in
benzonitrile, and its use as a fine powder is recommended.
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-p-tol-
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-(4-
1
octylphenyl)cyclopent-2-enecarboxylate-11h. 90% yield (97
ylcyclopent-2-enecarboxylate-11a. 90% yield (75 mg): H NMR
1
mg): H NMR DMSO-d6, 500 MHz, δ (ppm) 7.75 (s, 1H), 7.12
CD3OD, 250 MHz, δ (ppm) 7.10 (d, J = 8.6 Hz, 2H), 7.00 (d, J = 8.6,
2H), 5.98 (dd, J = 1.9 and 5.5, 1H), 5.81 (dd, J = 2.2 and 5.2, 1H),
4.03 (tt, J = 2.2 and 7.7, 1H), 3.72 (s, 3H), 3.31 (dd, peak underneath
residual CD3OD, 1H), 2.38 (s, 3H), 1.76 (dd, J = 7.4 and 13.5, 1H),
1.42 (s, 9H); 13C NMR CD3OD, 62.5 MHz, δ (ppm) 175.6, 157.6,
142.7, 141.0, 137.4, 132.1, 130.4, 128.4, 80.8, 72.39, 53.1, 50.2, 47.7,
28.9, 21.2; HRMS calcd for (C19H25NO4Na) 354.1681, found
354.1658.
(d, J = 8.5, 2H), 7.08 (d, J = 8.5, 2H), 5.97 (dd, J = 1.5 and 5.5, 1H),
5.83 (d, J = 3, 1H), 3.95 (t, J = 7.5, 1H), 3.61 (s, 3H), 3.09 (dd, J = 8.5
and 13.5, 1H), 2.51 (t, J = 7.5, 2H), 1.71 (dd, J = 7.5 and 13.5, 1H),
1.53 (qn, J = 7.5, 2H), 1.36 (s, 9H), 1.25 (m, 10H), 0.85 (t, J = 7.5,
3H); 13C NMR DMSO-d6, 125 MHz, δ (ppm) 174.0, 155.8, 142.2,
141.1, 139.2, 132.1, 129.1, 127.8, 127.7, 79.0, 71.0, 55.6, 50.1, 46.4,
1
35.5, 32.0, 31.7, 29.5, 29.4, 29.4, 22.4, 14.9; H NMR CD3OD, 250
MHz, δ (ppm) 7.09 (s, 4H), 5.98 (dd, J = 2 and 5.4, 1H), 5.82 (dd, J =
2.3 and 5.3, 1H), 4.03 (tt, J = 2 and 7.8, 1H), 3.71 (s, 3H), 3.29 (dd, J
= 8.3 and 13.3, 1H), 2.55 (t, J = 7.5, 2H), 1.78 (dd, J = 7.5 and 13.5,
1H), 1.57 (qn, J = 7, 2H), 1.41 (s, 9H), 1.28 (bs, 10H), 0.88 (t, J = 7.5,
3H); 13C NMR CD3OD, 62.5 MHz, δ (ppm) 175.5, 157.6, 143.0,
142.4, 141.0, 132.1, 129.8, 128.4, 80.6, 72.3, 53.1, 51.9, 47.6, 36.7, 33.2,
32.9, 30.7, 30.5, 30.5, 28.9, 23.8, 14.6; HRMS calcd for (C26H39NO4H)
430.2957, found 430.2932.
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-(4-
iodophenyl)cyclopent-2-enecarboxylate-11i. 58% yield (64 mg):
1H NMR CD3OD, 250 MHz, δ (ppm) 7.64 (d, J = 8.4, 2H), 7.00 (d, J
= 8.4, 2H), 6.00 (dd, J = 2.0 and 5.5, 1H), 5.86 (dd, J = 2.4 and 5.5,
1H), 4.05 (t, J = 7.8, 1H), 3.72 (s, 3H), 3.31 (dd, peak underneath
residual CD3OD, 1H), 1.76 (dd, J = 7.5 and 13.7, 1H), 1.42 (s, 9H);
13C NMR CD3OD, 62.5 MHz, δ (ppm) 175.2, 157.4, 145.5, 140.0,
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-(4-
ethylphenyl)cyclopent-2-enecarboxylate-11b. 56% yield (48
1
mg): H NMR CD3OD, 500 MHz, δ (ppm) 7.10 (s, 4H), 6.00 (dd,
J = 1.9 and 5.4, 1H), 5.83 (bs, 1H), 4.04 (tt, J = 2.2 and 7.9, 1H), 3.70
(s, 3H), 3.23 (dd, J = 8.2 and 13.5, 1H), 2.55 (q, J = 7.6, 2H), 1.77
(dd, J = 7.4 and 13.5, 1H), 1.43 (s, 9H), 1.22 (t, J = 7.5, 3H); 13C
NMR CD3OD, 150 MHz, δ (ppm) 175.6, 157.7, 144.0, 143.0, 141.0,
132.1, 129.2, 128.5, 80.7, 72.3, 53.1, 51.9, 47.6, 29.6, 28.9, 16.4; HRMS
calcd for (C20H27NO4Na) 368.1838, found 368.1851.
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-(4-
propylphenyl)cyclopent-2-enecarboxylate- 11c. 90% yield (75
mg): 1H NMR CD3OD, 250 MHz, δ (ppm) 7.10 (s, 4H), 6.00 (dd, J =
1.9 and 5.4, 1H), 5.83 (dd, J = 2.0 and 5.2, 1H), 4.04 (tt, J = 2.2 and
7.9, 1H), 3.70 (s, 3H), 3.23 (dd, J = 8.2 and 13.5, 1H), 2.55 (t, J = 7.6,
2H), 1.77 (dd, J = 7.4 and 13.5, 1H), 1.61 (sx, J = 7.5, 2H), 1.42 (s,
9H), 0.92 (t, J = 7.4, 3H); 13C NMR CD3OD, 125 MHz, δ (ppm)
175.6, 157.7, 143.1, 142.3, 141.0, 132.1, 129.8, 128.4, 80.7, 72.4, 53.1,
51.9, 47.5, 38.8, 28.9, 25.9, 14.2; HRMS calcd for (C21H29NO4H)
360.2175, found 360.2159.
138.8, 132.8, 130.7, 92.5, 80.6, 72.2, 53.2, 51.6, 47.2, 28.9; HRMS calcd
for (C18H22INO4Na) 466.0491, found 466.0474.
rac-(1S*,4R*)-tert-Butyl-1-(tert-butoxycarbonylamino)-4-(4-
iodophenyl)cyclopent-2-enecarboxylate-11j. 41% yield (50 mg):
1H NMR DMSO-d6, 500 MHz, δ (ppm) 7.7 (d, J = 8, 2H), 7.00 (d, J =
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-(4-
butylphenyl)cyclopent-2-enecarboxylate-11d. 71% yield (66
8.3 Hz, 2H), 5.92 (d, J= 6.0, 1H), 5.83 (bs, 1H), 3.95 (t, J = 7.5, 1H),
3.13 (dd, J = 8.3 and 13.5, 1H), 1.62 (dd, J = 7.3 and 13.5, 1H), 1.38
(bs, 18H); 13C NMR DMSO-d6, 62.5 MHz, δ (ppm) 172.4, 156.1,
144.3, 138.2, 137.4, 131.7, 129.2, 81.0, 78.9, 71.3, 50.4, 45.6, 27.4, 26.8;
HRMS calcd for (C21H28NO4IH) 486.1121, found 486.1141.
Obtained as a white solid after flash chromatography, mp 144−145 °C.
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-(2,4-
dimethoxyphenyl)cyclopent-2-enecarboxylate-11k. 70% yield
(66 mg): 1H NMR CD3OD, 500 MHz, δ (ppm) 6.98 (d, J = 8.3, 1H),
6.49 (d, J = 2.3, 1H), 6.45 (dd, J = 2.5 and 8.3, 1H), 5.98 (dd, J = 2.4
and 5.4, 1H), 5.81 (bs, 1H), 4.35 (tt, J = 2.2 and 7.4, 1H), 3.80 (s,
3H), 3.76 (s, 3H), 3.72 (s, 3H), 3.23 (dd, J = 8.2 and 13.5, 1H), 1.68
(dd, J = 7.2 and 13.5, 1H), 1.41 (s, 9H); 13C NMR CD3OD, 125 MHz,
δ (ppm) 175.7, 161.3, 159.3, 157.6, 140.8, 131.7, 128.9, 126.1, 105.8,
99.4, 80.6, 72.2, 56.0, 55.9, 53.1, 46.2, 44.6, 28.9; HRMS calcd for
(C20H27NO6H) 378.1917, found 378.1921.
1
mg): H NMR CD3OD, 250 MHz, δ (ppm) 7.10 (s, 4H), 5.99 (dd,
J = 1.9 and 5.4, 1H), 5.84 (dd, J = 2.0 and 5.2, 1H), 4.00 (tt, J = 2.0
and 7.7, 1H), 3.72 (s, 3H), 3.28 (peak underneath residual CD3OD,
1H), 2.57 (t, J = 7.6, 2H), 1.77 (dd, J = 7.4 and 13.5, 1H), 1.57 (qn, J =
7.6, 2H), 1.42 (s, 9H), 1.34 (sx, J = 7.7, 2H), 0.90 (t, J = 7.3, 3H); 13C
NMR CD3OD, 125 MHz, δ (ppm) 175.6, 157.6, 143.0, 142.4, 141.0,
132.1, 129.9, 128.4, 80.7, 72.3, 53.1, 51.9, 47.6, 36.4, 35.1, 28.9, 23.5,
14.4; HRMS calcd for (C22H31NO4H) 374.2331, found 374.2326.
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-(4-
pentylphenyl)cyclopent-2-enecarboxylate-11e. 80% yield (78
mg): 1H NMR CD3OD, 250 MHz, δ (ppm) 7.09 (s, 4H), 5.97 (dd, J =
1.9 and 5.4, 1H), 5.82 (dd, J = 2.0 and 5.2, 1H), 3.71 (s, 3H), 4.04 (t, J
= 7.4, 1H), 3.29 (dd, J = 8.4 and 13.4, 1H), 2.55 (t, J = 7.7, 2H), 1.77
(dd, J = 7.0 and 13.4, 1H), 1.58 (qn, J = 7.0, 2H), 1.41 (s, 9H), 1.30
(m, 4H), 0.89 (t, J = 7.0, 3H); 13C NMR CD3OD, 125 MHz, δ (ppm)
175.5, 157.5, 142.9, 142.4, 141.0, 132.1, 129.8, 128.4, 80.6, 72.3, 53.1,
51.9, 47.6, 36.6, 32.7, 32.6, 28.9, 23.7, 14.6; HRMS calcd for
(C23H33NO4H) 388.2488, found 388.2492.
rac-(1S*,4R*)-Methyl-1-(tert-butoxycarbonylamino)-4-(2,5-
dimethoxyphenyl)cyclopent-2-enecarboxylate-11l. 65% yield
1
(61 mg): H NMR CD3OD, 500 MHz, δ (ppm) 6.85 (d, J = 9.0,
8187
dx.doi.org/10.1021/jo3015209 | J. Org. Chem. 2012, 77, 8182−8190