PAPER
Unnatural Amino Acids via Allylpalladium Umpolung
3563
IR (neat): 3373 (br w), 1734 (s), 1512 (s), 1367 (w), 1037 (m), 856
cm–1 (w).
(2 C), (127.1), 117.5, 115.5 (2 C), 114.7 (2 C), 60.9, 60.7, 60.6,
55.5, (52.1), 52.0, 44.7, 44.6, 36.0, 35.7, 34.7, 34.7, 33.1, (32.7),
32.1, (31.8), (29.6), (29.5), 28.7, 28.2, 26.4, (25.7), 25.1, 23.0, 23.0,
(22.6), 14.0, 13.9, 10.7, 10.0; the additional peaks reported in the
13C NMR spectral data correspond to two diastereomers arising
from the stereocenter in the C-3 side chain (however, these diaste-
reomers could not be distinguished by 1H NMR spectroscopy), sig-
nals for the minor diastereomer are given in parentheses.
1H NMR (400 MHz, CDCl3): d = 7.41 (d, J = 8.2 Hz, 2 H), 7.33 (t,
J = 8.0 Hz, 2 H), 7.24 (t, J = 7.2 Hz, 1 H), 6.80 (d, J = 16.0 Hz, 1
H), 6.75 (d, J = 9.2 Hz, 2 H), 6.70 (d, J = 16.0 Hz, 1 H), 6.61 (d,
J = 8.8 Hz, 2 H), 5.42 (s, 0.8 H), 5.39 (s, 0.2 H), 5.16 (s, 0.8 H), 5.15
(s, 0.2 H), 4.15–3.99 (m, 4 H), 3.73 (s, 3 H), 3.04 (dt, J = 6.0, 9.2
Hz, 0.8 H), 2.97 (ddd, J = 4.8, 10.4 Hz, 0.2 H), 1.71–1.60 (br m, 2
H), 1.37–1.23 (br m, 8 H), 1.19 (t, J = 6.8 Hz, 3 H), 0.87 (t, J = 6.8
Hz, 3 H).
HRMS (ES+): m/z calcd for C30H42NO5 (M + H+): 496.3063; found:
496.3071.
13C NMR (100 MHz, CDCl3): d = 173.7, (173.4), 152.7, (145.1),
144.9, (141.5), 141.3, (137.2), 137.0, 130.4, (129.7), (128.9), 128.6
(2 C), 128.4, 127.6, (127.5), (126.5), 126.4 (2 C), (117.0), 116.8,
115.5 (2 C), 114.7 (2 C), (62.1), 61.4, 60.9, 55.6, (44.2), 43.9, 31.6,
31.4, (29.7), (29.6), (29.3), 29.2, 27.1, (27.0), 22.5, (14.2), 14.1,
14.0; signals for the minor diastereomer are given in parentheses.
Ethyl 3-(1-Cyclohexyl)-4-(4-methoxycarbonylphenyl)-2-[N-(4-
methoxyphenylamino]pent-4-enoate (Major Diastereomer) (1i)
Flash chromatography over silica gel (eluent: EtOAc–hexane, 1:10)
afforded the amine 1i (0.072 g, 69%) as a mixture of inseparable
diastereomers (dr = 25:1); yellow oil; Rf = 0.51 (EtOAc–hexane,
1:3).
HRMS (ES+): m/z calcd for C28H38NO3 (M + H+): 436.2853; found:
436.2846.
IR (neat): 3375 (br w), 1724 (s), 1607 (m), 1512 (s), 1436 (m), 822
cm–1 (m).
Ethyl 3-(1-Hexyl)-4-[(E)-oct-1-enyl]-2-[N-(4-methoxyphenyl-
amino]pent-4-enoate (Major Diastereomer) (1g)
Flash chromatography over silica gel (eluent: EtOAc–hexane, 1:22)
afforded the amine 1g (0.058 g, 58%) as a mixture of inseparable
diastereomers (dr = 2:1); yellow oil; Rf = 0.62 (EtOAc–hexane,
1:10).
1H NMR (400 MHz, CDCl3): d = 7.96 (d, J = 8.4 Hz, 2 H), 7.39 (d,
J = 8.4 Hz, 2 H), 6.75 (d, J = 9.2 Hz, 2 H), 6.62 (d, J = 8.8 Hz, 2 H),
5.54 (s, 1 H), 5.36 (s, 1 H), 4.26 (d, J = 4.4 Hz, 1 H), 3.92 (d, J = 4.4
Hz, 1 H), 3.91 (s, 3 H), 3.72 (s, 3 H), 3.57 (dq, J = 7.2, 10.8 Hz, 1
H), 3.25 (dq, J = 7.2, 10.8 Hz, 1 H), 3.01 (dd, J = 4.4, 10.0 Hz, 1 H),
2.04 (d, J = 12.0 Hz, 1 H), 1.94 (d, J = 12.0 Hz, 1 H), 1.78–1.75 (m,
4 H), 1.28–1.25 (m, 3 H), 1.13–1.00 (br m, 2 H), 0.81 (t, J = 7.2 Hz,
3 H).
13C NMR (100 MHz, CDCl3): d = 173.4, 166.7, 152.8, 148.3, 146.6,
141.2, 129.3 (2 C), 128.9, 126.9 (2 C), 117.4, 115.7 (2 C), 114.7 (2
C), 60.5, 56.4, 55.5, 52.0, 51.8, 38.2, 31.4, 30.9, 26.5, 26.4, 26.3,
13.6.
IR (neat): 3377 (br w), 1734 (s), 1514 (s), 1242 (s), 1039 (m), 966
cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 6.73 (d, J = 8.8 Hz, 2 H), 6.57 (d,
J = 8.8 Hz, 2 H), 6.01 (d, J = 16.0 Hz, 0.67 H), 5.87 (dt,
J = 6.8, 15.6 Hz, 0.33 H), 5.82 (dt, J = 6.8, 15.6 Hz, 1 H), 5.16 (s,
0.67 H), 5.11 (s, 0.33 H), 4.93 (s, 0.67 H), 4.91 (s, 0.33 H), 4.19–
4.02 (m, 2 H), 3.99 (d, J = 6.4 Hz, 0.33 H), 3.92 (d, J = 7.2 Hz, 0.67
H), 3.82 (br s, 1 H), 3.73 (s, 1 H), 3.72 (s, 2 H), 2.88–2.75 (m, 1 H),
2.12 (q, J = 6.8 Hz, 1 H), 2.07 (q, J = 6.8 Hz, 2 H), 1.72–1.65 (br m,
1 H), 1.63–1.47 (br m, 3 H), 1.44–1.22 (br m, 16 H), 1.22 (t, J = 7.2
Hz, 3 H), 0.89 (t, J = 3.2 Hz, 2 H), 0.87 (t, J = 7.2 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 173.9, (173.6), (152.7), 152.6,
(145.2), 145.1, (141.7), 141.5, 131.3, 130.9, 115.4, 115.2 (2 C),
114.7 (2 C), (114.4), 114.3, (62.0), 61.4, 60.7, 55.6, 44.7, 33.0,
(32.9), (31.7), 31.7, 31.7, 31.0, (29.5), (29.4), (29.3), 29.3, 29.2,
28.9, (28.8), 27.1, 22.6, 14.2, 14.1, 14.0; signals for the minor dia-
stereomer are given in parentheses.
HRMS (ES+): m/z calcd for C28H36NO5 (M + H+): 466.2594; found:
466.2580.
Ethyl 3-(2-Ethyl-1-hexyl)-4-[(E)-2-phenylethenyl)-2-[N-(4-
methoxyphenylamino]pent-4-enoate (Major Diastereomer) (1j)
Flash chromatography over silica gel (eluent: EtOAc–hexane, 1:20)
afforded the amine 1j (0.075 g, 76%) as a mixture of inseparable
diastereomers (dr = 7:1); yellow oil; Rf = 0.52 (EtOAc–hexane,
1:5).
IR (neat): 3377 (br w), 1732 (s), 1599 (w), 1512 (s), 1463 (m), 1037
(m), 962 cm–1 (m).
HRMS (ES+): m/z calcd for C28H46NO3 (M + H+): 444.3478; found:
444.3472.
1H NMR (500 MHz, CDCl3): d = 7.41 (d, J = 8.4 Hz, 2 H), 7.33 (t,
J = 8.0 Hz, 2 H), 7.24 (t, J = 7.2 Hz, 1 H), 6.78 (d, J = 16.4 Hz, 1
H), 6.74 (d, J = 8.8 Hz, 2 H), 6.70 (d, J = 16.0 Hz, 1 H), 6.61 (d,
J = 9.2 Hz, 2 H), 5.44 (s, 0.88 H), 5.40 (s, 0.12 H), 5.17 (s, 0.88 H),
5.16 (s, 0.12 H), 4.10 (dq, J = 7.2, 10.8 Hz, 1 H), 4.39 (dq,
J = 7.2, 10.8 Hz, 1 H), 3.98 (dd, J = 2.0, 6.4 Hz, 1 H), 3.88 (br s, 1
H), 3.73 (s, 3 H), 3.13 (ddd, J = 4.8, 6.0 Hz, 1 H), 1.75 (m, 1 H),
1.46–1.36 (br m, 2 H), 1.35–1.22 (br m, 8 H), 1.19 (t, J = 7.2 Hz, 3
H), 0.88–0.80 (m, 6 H).
Ethyl 3-(2-Ethyl-1-hexyl)-4-(4-methoxycarbonylphenyl)-2-[N-
[4-methoxyphenylamino]pent-4-enoate (Major Diastereomer)
(1h)
Flash chromatography over silica gel (eluent: EtOAc–hexane, 1:12)
afforded the amine 1h (0.091 g, 81%) as a mixture of inseparable
diastereomers (dr = 25:1); colorless greasy solid; Rf = 0.43 (EtOAc–
hexane, 1:5).
13C NMR (100 MHz, CDCl3): d = 173.6, 173.6, (173.4), 152.7,
(145.1), 145.0, 145.0, (141.6), (141.6), 141.3, 141.3, (137.2), 137.0,
(130.2), (130.2), 128.6 (2 C), 127.6, 126.5 (2 C), 126.5 (2 C),
(117.1), (117.0), 115.5 (2 C), 114.7 (2 C), (62.5), 61.9, 61.9, (60.9),
60.9, 55.6, 41.8, 41.7, 36.1 (36.0), 35.7, (35.4), 35.2, 35.1, 33.2,
(33.0), 32.2, (32.1), (29.6), (29.0), 28.8, 28.2, (28.1), (26.8), 26.5,
25.2, (24.9), 23.1, (23.0), 23.0, (14.2), 14.1, 14.1, (11.1), 10.9, 10.1,
(9.8); the additional peaks reported in the 13C NMR spectral data
correspond to two diastereomers arising from the stereocenter in the
C-3 side chain (however, these diastereomers could not be distin-
IR (neat): 3377 (w), 1724 (s), 1606, (m), 1514 (s), 1111 (s), 910
cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 7.99 (d, J = 8.4 Hz, 2 H), 7.36 (d,
J = 8.4 Hz, 2 H), 6.73 (d, J = 9.2 Hz, 2 H), 6.54 (d, J = 8.8 Hz, 2 H),
5.44 (s, 1 H), 5.31 (s, 1 H), 3.91 (s, 3 H), 3.90 (m, 2 H), 3.84 (dq,
J = 6.8, 10.8 Hz, 1 H), 3.75 (dq, J = 6.8, 10.8 Hz, 1 H), 3.72 (s, 3 H),
3.26–3.22 (m, 1 H), 1.67 (dt, J = 2.0, 10.0 Hz, 1 H), 1.45–1.37 (br
m, 3 H), 1.34–1.15 (br m, 5 H), 1.06 (dt, J = 1.6, 6.8 Hz, 3 H), 0.89–
0.86 (m, 5 H), 0.82 (t, J = 7.2 Hz, 3 H).
1
guished by H NMR spectroscopy), signals for the minor diaste-
13C NMR (100 MHz, CDCl3): d = 173.1, 173.0, 166.7, 152.7, 147.8,
147.8, 147.0, 146.9, 140.8, 140.8, (130.1), 129.4 (2 C), 129.0, 127.2
reomer are given in parentheses.
Synthesis 2007, No. 22, 3558–3566 © Thieme Stuttgart · New York