K. Fuhshuku, Y. Asano / Tetrahedron 68 (2012) 6651e6655
6653
rotation values were measured on a Horiba SEPA-300. IR spectra
were recorded on a PerkineElmer spectrum 100 spectrometer. 1H
and 13C NMR spectra were recorded on a Bruker Biospin Avance II
400 spectrometer (TMS and/or residual solvents as an internal
standard). Mass spectra were recorded on a Bruker Daltonics
micrOTOF. All chemicals were purchased from commercial sources
and used without further purification.
(R)-18: 98% from (R)-9 and 14 as a colorless oil, ½a D21
ꢂ
¼þ11.5
(c 1.37, CHCl3); IR (ATR) nmax 3304, 2977, 1704, 1636, 1445, 1165, 913,
731, 698 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d 1.41 (3.96H, s), 1.44
(5.04H, s), 1.55e1.79 (2H, m), 2.00e2.07 (2H, m), 2.27e2.43 (1.44H,
m), 2.51 (0.56H, ddd, J¼6.8, 7.2, 14.0 Hz), 3.21e3.32 (1.56H, m),
3.37e3.45 (0.44H, m), 4.36 (0.56H, d, J¼14.9 Hz), 4.57 (0.44H, d,
J¼16.9 Hz), 4.65 (0.44H, d, J¼16.9 Hz), 4.65e4.70 (1H, m), 4.85
(0.56H, d, J¼14.9 Hz), 4.94e5.16 (4H, m), 5.31e5.35 (1H, m),
5.63e5.83 (2H, m), 7.18e7.36 (5H, m); 13C NMR (100 MHz, CDCl3)
4.2. General procedure for the synthesis of N0-alkenyl-N-
Boc-allylglycine derivatives (15e19)
d
26.4, 27.7, 28.28, 28.32, 30.7, 31.0, 37.8, 38.1, 45.8, 46.4, 48.5, 49.9,
50.0, 51.0, 79.6, 115.1, 115.8, 118.5, 118.6, 126.8, 127.4, 127.8, 127.9,
128.6, 128.9, 132.81, 132.83, 136.5, 137.0, 137.2, 137.7, 155.3, 172.0;
HRMS (ESI): m/z calculated for C22H32N2O3Naþ [MþNa]þ:
395.2305, found: 395.2317.
To an ice-cooled solution of N-Boc-allylglycine derivative (9 or
10) (20.0 mmol) and amine (11e14) (30.0 mmol) in dry CH2Cl2
(20.0 mL) were added EDC$HCl (30.0 mmol), HOBt$H2O
(20.0 mmol), and iPr2NEt (30.0 mmol). The reaction mixture was
stirred for 36 h at room temperature and diluted with water. After
extraction with EtOAc, the combined organic extract was washed
with brine, dried over MgSO4, and concentrated in vacuo. The
residue was purified by silica gel column chromatography (50 g).
Elution with hexaneeEtOAc (10:1 to 4:1) afforded the N0-alkenyl-N-
Boc-allylglycine derivative (15e19) as a mixture of two rotamers.
(S)-18: 94% from (S)-9 and 14 as a colorless oil, ½a D21
ꢂ ¼ꢀ11.7
(c 1.42, CHCl3). Its IR and NMR spectra were identical with those of
(R)-18.
(R)-19: 98% from (R)-10 and 12 as a colorless oil, ½a D20
ꢂ ¼þ61.9
(c 1.02, CHCl3); IR (ATR) nmax 3323, 2974,1709,1634,1442,1164, 916,
740, 699 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d 1.06 (1.08H, s), 1.08
(1.08H, s), 1.10 (1.92H, s), 1.11 (1.92H, s), 1.42 (3.24H, s), 1.43 (5.76H,
s), 3.53 (0.36H, dd, J¼7.1, 15.1 Hz), 3.91 (0.64H, dd, J¼6.3, 17.1 Hz),
4.06 (0.64H, dd, J¼3.6, 17.1 Hz), 4.24 (0.64H, d, J¼14.7 Hz), 4.38
(0.36H, dd, J¼6.7, 15.1 Hz), 4.39 (0.36H, d, J¼16.4 Hz), 4.52 (0.64H, d,
J¼9.9 Hz), 4.68 (0.36H, d, J¼9.9 Hz), 4.84 (0.36H, d, J¼16.4 Hz), 4.92
(0.64H, d, J¼14.7 Hz), 5.03e5.24 (4.36H, m), 5.28 (0.64H, d,
J¼9.9 Hz), 5.32 (0.36H, d, J¼9.9 Hz), 5.67e5.85 (1H, m), 5.97 (0.36H,
dd, J¼10.6, 17.4 Hz), 5.99 (0.64H, dd, J¼10.4, 17.8 Hz), 7.20e7.32 (5H,
a 21
(R)-15: 75% from (R)-9 and 11 as a colorless oil, ½ ꢂD ¼ꢀ15.6
(c 1.46, CHCl3); IR (ATR) nmax 3303, 2978, 1704, 1636, 1485, 1408,
1165, 915 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d 1.42 (3.78H, s), 1.43
(5.22H, s), 2.30e2.38 (1H, m), 2.43e2.52 (1H, m), 2.93 (1.26H, s),
3.03 (1.74H, s), 3.90e3.98 (1H, m), 4.02e4.10 (1H, m), 4.60e4.65
(0.42H, m), 4.66e4.72 (0.58H, m), 5.08e5.26 (4H, m), 5.34 (0.42H,
d, J¼8.5 Hz), 5.41 (0.58H, d, J¼8.3 Hz), 5.67e5.85 (2H, m); 13C NMR
(100 MHz, CDCl3)
d
28.2, 33.6, 34.6, 37.5, 37.9, 49.7, 49.9, 50.3, 52.0,
m); 13C NMR (100 MHz, CDCl3)
d 22.8, 23.0, 24.3, 24.4, 28.2, 28.3,
79.4, 117.46, 117.48, 118.3, 118.5, 132.4, 132.7, 132.9, 155.1, 155.2,
171.3, 171.8; HRMS (ESI): m/z calculated for C14H24N2O3Naþ
[MþNa]þ: 291.1679, found: 291.1671.
41.1, 41.3, 47.5, 47.9, 49.8, 50.9, 55.7, 79.5, 113.48, 113.51, 117.79,
117.84, 127.3, 127.4, 127.7, 128.2, 128.5, 128.7, 132.6, 132.7, 136.2,
137.2, 143.66, 143.69, 155.35, 155.43, 171.5, 171.8; HRMS (ESI):
m/z calculated for C22H32N2O3Naþ [MþNa]þ: 395.2305, found:
395.2309.
(S)-15: 75% from (S)-9 and 11 as a colorless oil, ½a D20
ꢂ ¼þ15.5
(c 1.48, CHCl3). Its IR and NMR spectra were identical with those of
(R)-15.
(S)-19: 99% from (S)-10 and 12 as a colorless oil, ½a D21
ꢂ ¼ꢀ61.6 (c
(R)-16: 94% from (R)-9 and 12 as a colorless oil, ½a D21
ꢂ
¼þ18.7
1.14, CHCl3). Its IR and NMR spectra were identical with those of (R)-
19.
(c 1.00, CHCl3); IR (ATR) nmax 3310, 2978, 1703, 1635,1444, 1165, 917,
732, 698 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d 1.42 (2.79H, s), 1.44
(6.21H, s), 2.29e2.45 (1.33H, m), 2.51 (0.67H, ddd, J¼6.8, 7.3,
14.1 Hz), 3.87e4.11 (2H, m), 4.48 (0.67H, d, J¼14.8 Hz), 4.61e4.75
(1.66H, m), 4.72 (0.67H, d, J¼14.8 Hz), 5.04e5.26 (4H, m), 5.33e5.35
(1H, m), 5.64e5.82 (2H, m), 7.19e7.37 (5H, m); 13C NMR (100 MHz,
4.3. (R)- and (S)-20
To a solution of (R)-15 (1.35 g, 5.03 mmol) in CH2Cl2 (500 mL)
was added a first generation Grubbs catalyst (412 mg, 0.501 mmol).
The reaction mixture was stirred for 72 h at reflux, then concen-
trated in vacuo. The residue was filtered through silica gel and
washed with hexaneeEtOAc, and the combined filtrate was con-
centrated in vacuo. The residue was dissolved in EtOH (50.0 mL),
and a catalytic amount of Pd/C (10% on carbon) was added. The
reaction mixture was vigorously stirred for 24 h at room temper-
ature under H2 and filtered through a Celite pad. The filter cake was
washed with EtOAc, and the combined filtrate was concentrated in
vacuo. The residue was purified by silica gel column chromatog-
raphy (50 g). Elution with hexaneeEtOAc (10:1 to 4:1) afforded
(R)-20 (1.02 g, 84%). Further purification by recrystallization from
hexaneeEtOAc afforded an analytical sample of (R)-20 as colorless
CDCl3) d 28.27, 28.29, 37.8, 37.9, 47.9, 48.2, 49.1, 49.9, 50.0, 50.1, 79.6,
117.7, 117.8, 118.6, 126.9, 127.4, 127.8, 128.0, 128.6, 128.8, 132.4, 132.5,
132.76, 132.81, 136.2, 136.9, 155.2, 155.3, 172.0, 172.2; HRMS (ESI):
m/z calculated for C20H28N2O3Naþ [MþNa]þ: 367.1992, found:
367.1996.
(S)-16: 95% from (S)-9 and 12 as a colorless oil, ½a D20
ꢂ ¼ꢀ18.9
(c 1.18, CHCl3). Its IR and NMR spectra were identical with those of
(R)-16.
(R)-17: 95% from (R)-9 and 13 as a colorless oil, ½a D20
ꢂ ¼þ18.9
(c 1.48, CHCl3); IR (ATR) nmax 3307, 2978,1703, 1636,1448,1165, 915,
730, 698 cmꢀ1 1H NMR (400 MHz, CDCl3)
; d 1.41 (3.78H, s), 1.44
(5.22H, s), 2.24e2.43 (3.42H, m), 2.52 (0.58H, ddd, J¼6.7, 7.3,
14.0 Hz), 3.28e3.38 (1.58H, m), 3.52 (0.42H, ddd, J¼6.7, 7.3, 14.0 Hz),
4.37 (0.58H, d, J¼15.0 Hz), 4.57 (0.42H, d, J¼16.7 Hz), 4.66 (0.42H, d,
J¼16.7 Hz), 4.65e4.73 (1H, m), 4.86 (0.58H, d, J¼15.0 Hz), 5.00e5.17
(4H, m), 5.31e5.35 (1H, m), 5.64e5.83 (2H, m), 7.18e7.36 (5H, m);
crystals, mp 110 ꢁC; ½a D20
ꢂ
¼ꢀ28.5 (c 1.26, CHCl3); IR (ATR) nmax 3395,
1H NMR
d 1.33e1.54 (2H, m), 1.44 (9H, s), 1.72e1.82
2924, 1703, 1637, 1480, 1437, 1162, 1053, 1015 cmꢀ1
(400 MHz, CDCl3)
;
13C NMR (100 MHz, CDCl3)
d
28.27, 28.30, 31.8, 33.1, 37.8, 38.1, 45.5,
(2H, m),1.93e2.05 (2H, m), 3.02 (3H, s), 3.18 (1H, dd, J¼5.4,15.2 Hz),
46.3, 48.6, 49.9, 50.0, 51.2, 79.5, 79.6, 116.9, 117.9, 118.5, 118.6, 126.8,
127.4, 127.8, 127.9, 128.6, 128.8, 132.8, 133.9, 135.1, 136.3, 137.1, 155.1,
155.2, 172.0, 172.1; HRMS (ESI): m/z calculated for C21H30N2O3Naþ
[MþNa]þ: 381.2149, found: 381.2142.
3.58 (1H, dd, J¼11.8, 15.2 Hz), 4.38 (1H, dd, J¼5.6, 11.0 Hz), 6.00
(1H, br); 13C NMR (100 MHz, CDCl3)
d 26.6, 27.8, 28.4, 32.4, 36.0,
50.4, 53.1, 79.2, 155.1, 173.0; HRMS (ESI): m/z calculated for
C12H22N2O3Naþ [MþNa]þ: 265.1523, found: 265.1512.
(S)-17: 90% from (S)-9 and 13 as a colorless oil, ½a D20
ꢂ
¼ꢀ18.9
In the same manner as described above, (S)-15 was converted to
(S)-20. Further purification by recrystallization from hexaneeEtOAc
afforded an analytical sample of (S)-20 as colorless crystals, mp
(c 1.12, CHCl3). Its IR and NMR spectra were identical with those of
(R)-17.