Cyclic Quaternary a-Amino Acid Derivatives
FULL PAPER
from 4a (700 mg) and 3-(perfluorooctyl)propanol. 1H NMR (300 MHz,
CDCl3): d=1.69–1.74 (m, 4H), 2.93–3.07 (m, 2H), 3.71 (s, 3H), 4.11 (t,
J=5.5 Hz, 2H), 5.21–5.28 (m, 2H), 5.74–5.85 (m, 1H), 6.79 (d, J=9.1 Hz,
2H), 6.85 ppm (d, J=9.0 Hz, 2H); 13C NMR (CDCl3, 75.5 MHz): d=19.5
(CH), 59.1 (CH3), 63.8 (CH2), 77.9 (CH2), 122.1 (Ct, 3J
122.5 (Ct, 1J
(C,F)=250.1 Hz), 123.8 (CH), 127.6 (CH), 127.7 (CH), 128.5
A
AHCTREUNG
(CH), 141.8 (C), 170.5 ppm (C) (the signals from the C8F17 group were
obscured due to their low intensity); 19F NMR (CDCl3, 282.4 MHz): d=
(Ct, 3J
24.2 Hz), 55.2 (CH3), 64.3 (CH2), 114.3 (CH), 118.5 (Ct, 1J
244.9 Hz), 121.3 (CH), 121.4 (CH2), 127.8 (Ct, 3J
(C,F)=4.9 Hz), 140.2
(C), 154.5 (Ct, 2J
(C,F)=33.9 Hz), 158.7 (C), 162.2 ppm (C) (the signals
from the C8F17 group were obscured due to their low intensity); 19F NMR
(CDCl3, 282.4 MHz): d=À83.28 (t, (F,H)=9.8 Hz, 2F), À102.4 (t,
A
G
A
À81.25 (d, 3J
C
G
(F,H)=
C
20.7, J2
U
N
ACHTREUNG
G
1F), À114.90 (t, 3J
(F,F)=13.8 Hz, 2F), À122.39 (brs, 2F), À123.21 (brs,
G
N
2F), À123.98 (brs, 2F), À126.59 ppm (brs, 2F); HRMS: m/z: calcd for
C27H25NO3F19: 772.1531 [M+H]+; found 772.1556.
J
ACHTREUNG
(À)-(E)-2-[(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Heptadecafluoroundecyl)
J
A
dimethylsilyl]ethyl
3,3-difluoro-2-{[(1R)-1-phenyl-2-methoxyethyl]imi-
(brs, 2F), À125.94 (brs, 2F), À128.67 ppm (t, J=9.3 Hz, 2F); HRMS:
no)}-5-hexenoate [(À)-20]: By means of the general procedure described
above for the preparation of fluorinated a-imino esters 5, compound (À)-
20 was obtained as a yellow oil (930 mg) in 55% yield from 4c (728 mg)
and fluorous trimethylsylilethanol (FTMSOH). [a]D25 =À14.62 (c 1.6
CHCl3); 1H NMR (300 MHz, CDCl3): d=0.00 (s, 6H), 0.52–0.58 (m,
2H), 0.98–1.05 (m, 2H), 1.48–1.60 (m, 2H), 1.92–2.07 (m, 2H), 2.85–3.00
(m, 2H), 3.25 (s, 3H), 3.57 (d, J=6.4 Hz, 2H), 4.27–4.33 (m, 2H), 4.81 (t,
m/z: calcd for C24H18F19NO3: 729.0983 [M]+, found 729.1076.
(À)-(E)-4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Heptadecafluoroundecyl 3,3-
difluoro-2-{[(1R)-1-phenyl-2-methoxyethyl]imino)}-5-hexenoate (17b): 3-
(Perfluorooctil)propil iodide (0.58 mmol) and TBAF (0.35 mmol) were
added to a solution of silylated a-imino ester 5h (0.29 mmol) in dry THF
(2 mL) at 08C. The reaction mixture was stirred at room temperature
until TLC indicated the total disappearance of the starting material. The
solvents were then removed under reduced pressure and the residue was
purified by means of fluorous solid phase extraction (F-SPE). 17b was
obtained as a yellow oil (190 mg) in 86% yield. [a]2D5 =À13.15 (c 1.4
CHCl3); 1H NMR (300 MHz, CDCl3): d=1.92–2.03 (m, 2H), 2.09–2.18
(m, 2H), 2.85–3.00 (m, 2H), 3.23 (s, 3H), 3.57 (d, J=6.4 Hz, 2H), 4.27–
4.33 (m, 2H), 4.80 (dd, J1 =7.5, J2 =5.1 Hz, 1H), 5.15 (dd, Jtrans =17.1,
J=6.4 Hz, 1H), 5.16 (dd, Jtrans =17.7, Jcis =9.6 Hz, 2H), 5.74 (ddt, Jtrans
17.1,
cis =10.2, J3 =6.9 Hz, 2H), 7.22–7.31 ppm (m, 5H); 13C NMR
(CDCl3, 75.5 MHz): d=À3.6 (CH3), 14.7 (Cd, J
15.8 (CH2), 34.4 (Ct, 2J(C,F)=21.8 Hz), 39.6 (Ct, 2J
(CH), 64.1 (CH2), 67.2 (CH3), 77.4 (CH2), 118.5 (Ct, 1J
120.9 (CH2), 127.2 (CH), 127.8 (CH), 128.1 (CH), 128.5 (CH), 156.9 (Ct,
2J
(C,F)=33.9 Hz), 161.4 ppm (C) (the signals from the C8F17 group were
obscured due to their low intensity); 19F NMR (CDCl3, 282.4 MHz): d=
=
J
3
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
AHCTREUNG
J
cis =10.2 Hz, 2H), 5.65–5.79 (m, 1H), 7.24–7.28 ppm (m, 5H); 13C NMR
(CDCl3, 75.5 MHz): d=14.3 (CH2), 27.9 (Ct, 2J
(C,F)=23.1 Hz), 39.7 (Ct,
2J
(C,F)=24.7 Hz), 59.3 (CH), 64.3 (CH2), 67.7 (CH3), 77.5 (CH2), 121.2
U
À81.26 (s, 3F), À99.07 (ddd,
J
A
G
G
N
14.7 Hz, 1F), À101.05 (ddd,
J
A
G
ACHTREUNG
(CH2), 127.4 (CH), 128.2 (CH), 128.3 (CH), 128.9 (CH), 138.5 (C),
161.2 ppm (C), (the signals from the C8F17 and CF2 groups were obscured
due to their low intensity); 19F NMR (CDCl3, 282.4 MHz): d=À81.23 (t,
16.4 Hz, 1F), À114.93 (t, 3J
(F,F)=14.6 Hz, 2F), À122.24–(À126.65) ppm
G
(m, 12F); HRMS: m/z: calcd for C30H33SiO3NF19: 844.1926 [M+H]+;
found 844.1942.
3J
J2
C
J
G
E
(S)-2-[(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Heptadecafluoroundecyl) di-
methylsilyl]ethyl 2-allyl-3,3-difluoro-2-{[(1R)-1-phenyl-2-methoxyethyl]-
A
ACHTREUNG
A
À123.95 (brs, 2F), À126.58 ppm (brs, 2F); HRMS: m/z: calcd for
scribed above for the preparation of fluorinated dialkylated a-amino
esters 6 (Method A), (À)-21 was obtained as a pale yellow oil (84 mg) in
88% yield from (À)-20 (88 mg). [a]2D5 =À3.4 (c 1 CHCl3); 1H NMR
(300 MHz, CDCl3): d=0.00 (s, 6H), 0.53–0.58 (m, 2H), 0.82–0.90 (m,
2H), 1.50–1.61 (m, 2H), 1.95–2.13 (m, 2H), 2.41–2.71 (m, 2H), 2.84–3.01
(m, 2H), 3.29 (s, 3H), 3.36–3.43 (m, 2H), 3.92–4.02 (m, 2H), 4.15–4.19
(m, 2H), 4.85 (dd, J1 =15, J2 =12 Hz, 2H), 5.09 (d, J=17.1 Hz, 1H), 5.15
(d, J=10.2 Hz, 1H), 5.38–5.49 (m, 1H), 5.79 (ddt, Jtrans =17.1, Jcis =10.2,
J3 =7.0 Hz, 1H), 7.18–7.28 ppm (m, 5H); 13C NMR (CDCl3, 75.5 MHz):
C26H23NO3F19: 758.1376 [M+H]+; found 758.1420.
(S)-4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Heptadecafluoroundecyl 2-allyl-
3,3-difluoro-2-{[(1R)-1-phenyl-2-methoxyethyl]amino)}-5-hexenoate
(18b): By means of the general procedure described above for the prepa-
ration of fluorinated dialkylated a-amino esters 6 (Method A), 18b was
obtained as a pale yellow oil (90 mg) in 90% yield from 17b (97 mg).
[a]2D5 =À7.04 (c 0.8 CHCl3); 1H NMR (300 MHz, CDCl3): d=1.78–1.85
(m, 2H), 1.95–2.10 (m, 2H), 2.39–2.67 (m, 2H), 2.77–2.95 (m, 2H), 3.08
(s, 3H), 3.36–3.39 (m, 2H), 3.91–3.96 (m, 2H), 4.12 (t, J=6.4 Hz, 1H),
4.82 (d, J=12.2 Hz, 2H), 5.04 (d, J=17.1 Hz, 1H), 5.11 (d, J=10.2 Hz,
1H), 5.36–5.47 (m, 1H), 5.70 (ddt, Jtrans =17.1, Jcis =10.2, J3 =7.0 Hz, 1H),
7.18–7.24 ppm (m, 5H); 13C NMR (CDCl3, 75.5 MHz): d=19.9 (CH2),
d=À3.3 (CH3), 15.0 (CH2), 15.3 (CH2), 15.8 (CH2), 34.5 (Ct, 2J
C
G
69.5 (Ct, 2J
(C,F)=17.4 Hz), 78.2 (CH2), 118.4 (CH2), 120.3 (CH2), 127.5
G
(CH), 127.9 (CH), 128.4 (CH), 129.2 (CH), 133.0 (CH), 142.8 (C),
170.9 ppm (C) (the signals from the C8F17 and CF2 groups were obscured
due to their low intensity); 19F NMR (CDCl3, 282.4 MHz): d=À81.28 (d,
28.0 (Ct, 2J
(CH), 59.2 (CH3), 64.2 (CH2), 69.5 (Ct, 2J
118.4 (CH2), 120.5 (CH2), 127.6 (CH), 127.9 (CH), 128.4 (CH), 128.9 (Ct,
3J
(C,F)=4.6 Hz), 132.9 (CH), 142.5 (C), 170.8 ppm (C) (the signals from
A
N
AHCTREUNG
3J
J2
J2
C
J
G
ACHTREUNG
H
J
A
ACHTREUNG
the C8F17 and CF2 groups were obscured due to their low intensity);
19F NMR (CDCl3, 282.4 MHz): d=À81.25 (s, 3F), À100.83 (ddd, J
A
6F), À123.22 (brs, 2H), À124.11 (brs, 2F), À126.60 ppm (brs, 2F);
254.3, J1
J1
(F,H)=30.2, J2
R
N
HRMS: m/z: calcd for C33H39SiO3NF19:
886.2396 [M+H]+; found
(F,H)=29.7, J2
G
U
886.2350.
À122.40 (brs, 6F), À123.21 (brs, 2F), À124.05 (brs, 2F), À126.60 ppm
(brs, 2F); HRMS: m/z: calcd for C29H29NO3F19: 800.1844 [M+H]+;
found 800.1855.
(S)-2-[(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Heptadecafluoroundecyl) di-
methylsilyl]ethyl 6,6-difluoro-1-{[(1R)-1-phenyl-2-methoxyethyl]amino)}-
3-cyclohexene-1-carboxylate [(À)-22]: By means of the general procedure
described above for the preparation of compounds 8, (À)-22 was ob-
(S)-4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Heptadecafluoroundecyl
6,6-di-
fluoro-1-{[(1R)-1-phenyl-2-methoxyethyl]amino)}-3-cyclohexene-1-car-
boxylate (19b): By means of the general procedure described above for
the preparation of fluorinated cyclic a-amino esters 8, 19b was obtained
as a brown oil (57 mg) in 92% yield from 18b (64 mg). [a]2D5 =À16.06 (c
1 CHCl3); 1H NMR (300 MHz, CDCl3): d=1.62–1.71 (m, 2H), 1.84–1.99
(m, 2H), 2.39–2.47 (m, 2H), 2.72–2.80 (m, 2H), 3.22 (s, 3H), 3.35 (d, J=
6.5 Hz, 2H), 3.56–3.67 (m, 1H), 3.79–3.91 (m, 2H), 5.45–5.58 (m, 2H),
7.16–7.21 ppm (m, 5H); 13C NMR (CDCl3, 75.5 MHz): d=19.8 (CH2),
tained as a brown oil (54 mg) in 90% yield from (À)-21 (60 mg). [a]D25
=
À7.58 (c 0.32 CHCl3); 1H NMR (300 MHz, CDCl3): d=0.00 (S, 6H),
0.52–0.58 (m, 2H), 0.76–0.82 (m, 2H), 1.52–1.63 (m, 2H), 1.98–2.13 (m,
2H), 2.42–2.50 (m, 2H), 2.77–2.88 (m, 2H), 3.28 (s, 3H), 3.42 (d, J=
6.4 Hz, 2H), 3.73–3.98 (m, 3H), 5.51–5.68 (m, 2H), 7.23–7.29 ppm (m,
5H); 13C NMR (CDCl3, 75.5 MHz): d=À3.7 (CH3), 14.6 (Ct, 3J
G
57.1 (CH), 58.7 (CH3), 63.2 (CH2), 63.8 (Ct, 2J
(CH2), 121.7 (Ct, 3J(C,F)=5.2 Hz), 122.3 (Ct, 1J
(C,F)=250.1 Hz), 127.1
A
27.8 (Ct, 2J
G
G
A
ACHTREUNG
Chem. Eur. J. 2008, 14, 7019 – 7029
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7027