ꢀ
ꢀ
C. Berube et al. / Tetrahedron 71 (2015) 8077e8084
8081
128.3, 128.5, 128.8, 129.1, 132.0, 137.8, 158.2, 166.9, 168.1; HRMS
(ESI-TOF, m/z) calcd for C22H27N2O3 (MþH)þ¼367.2016, found
367.2022.
0.84 (d, J¼6.5 Hz, 6H), 1.35e1.45 (m, 2H) 1.49e1.57 (m, 2H)
1.70e1.81 (m, 2H), 3.64e3.69 (m, 2H) 8.14 (s, 2H); 13C NMR
(100 MHz, DMSO-d6):
d
¼22.3, 23.7, 24.3, 44.3, 53.3, 169.2; HRMS
(ESI-TOF, m/z) calcd for C12H23N2O2 (MþH)þ¼227.1754, found
4.2.1.8. (3R,6R)-3-(Benzyloxymethyl)-6-isopropylpiperazine-2,5-
227.1764.
dione (4). White powder; 1H NMR (400 MHz, DMSO-d6):
d
¼0.78 (d,
J¼6.9 Hz, 3H), 0.89 (d, J¼6.9 Hz, 3H), 2.08e2.17 (m, 1H), 3.53 (dd,
J¼9.7, 2.8 Hz, 1H), 3.58e3.60 (m, 1H), 3.76 (dd, J¼9.7, 2.8 Hz, 1H),
3.89e3.92 (m, 1H), 4.45 (dd, J¼5.5, 9.3 Hz, 1H), 7.20e7.32 (m, 5H),
4.2.1.16. (3S,6S)-3,6-Diisobutylpiperazine-2,5-dione
(12).30 White powder; 1H NMR (400 MHz, DMSO-d6):
d
¼0.81 (d,
J¼6.5 Hz, 6H), 0.84 (d, J¼6.5 Hz, 6H), 1.35e1.45 (m, 2H) 1.49e1.57
8.06 (s, 1H), 8.07 (s, 1H); 13C NMR (100 MHz, DMSO-d6):
d
¼17.3,
(m, 2H) 1.70e1.81 (m, 2H), 3.64e3.69 (m, 2H) 8.14 (s, 2H); 13C NMR
19.0, 55.6, 60.1, 71.8, 73.1, 128.0, 128.1, 128.9, 138.8; 167.4, 168.3;
HRMS (ESI-TOF, m/z) calcd for C15H21N2O3 (MþH)þ¼277.1547,
found 277.1567.
(100 MHz, DMSO-d6):
d
¼22.3, 23.7, 24.3, 44.3, 53.3, 169.2; HRMS
(ESI-TOF, m/z) calcd for C12H23N2O2 (MþH)þ¼227.1754, found
227.1762.
4.2.1.9. (3S,6S)-3-Benzyl-6-(benzyloxymethyl)piperazine-2,5-
4.2.1.17. (3R,6S)-3,6-Diisobutylpiperazine-2,5-dione
dione (5).25 White powder; 1H NMR (400 MHz, DMSO-d6):
d¼2.59
(13).31 White powder; 1H NMR (400 MHz, DMSO-d6):
d
¼0.81 (d,
(dd, J¼9.7, 6.4 Hz, 1H), 2.86 (dd, J¼13.9, 5.0 Hz, 1H), 3.0 (dd, J¼13.5,
5.7 Hz, 1H), 3.23 (dd, J¼9.6, 3.0 Hz, 1H), 3.76e3.81 (m, 1H)
4.02e4.08 (m, 1H), 4.26 (s, 2H), 7.03 (d, J¼6.9 Hz, 2H), 7.13e7.32 (m,
J¼6.3 Hz, 6H), 0.83 (d, J¼6.3 Hz, 6H), 1.40e1.59 (m, 4H), 1.69e1.83
(m, 2H), 3.67e3.74 (m, 2H), 8.00 (s, 2H); 13C NMR (100 MHz, DMSO-
d6):
d
¼22.6, 23.5, 24.2, 42.0, 53.1, 169.4; HRMS (ESI-TOF, m/z) calcd
8H), 8.07 (s, 2H); 13C NMR (100 MHz, DMSO-d6):
72.2, 72.8, 127.2, 128.2, 128.3; 128.8, 128.9, 130.7, 137.1, 138.6, 165.7,
d
¼40.1, 55.6, 56.1,
for C12H23N2O2 (MþH)þ¼227.1754, found 227.1762.
167.1;
HRMS
(ESI-TOF,
m/z)
calcd
for
C
19H21N2O3
4.2.1.18. (3S,6S)-3-Benzyl-6-(
r
-(benzyloxy)benzyl)piperazine-2,5-
(MþH)þ¼325.1547, found 325.1555.
dione (14).32 White powder; 1H NMR (400 MHz, DMSO-d6):
d
¼2.14
(dd, J¼13.8, 6.1 Hz, 1H), 2.22 (dd, J¼13.8, 6.1 Hz, 1H), 2.48e2.57 (m,
2H), 3.84e3.89 (m, 1H) 3.90e3.95 (m, 1H), 5,00 (s, 2H) 6.84e6.92
(m, 4H), 6.99 (d, J¼6.7 Hz, 2H), 7.12e7.35 (m, 8H), 7.84 (m, 2H); 13C
4. 2.1.10. (3S, 6S)-3, 6-Dibenzylpiperazine-2, 5-dione
(6).26e28 White powder; 1H NMR (400 MHz, DMSO-d6):
d
¼2.18 (dd,
J¼14.1, 6.1 Hz, 2H), 2.52 (dd, J¼13.6, 4.9 Hz, 2H), 3.89e3.95 (m, 2H),
NMR (100 MHz, DMSO-d6):
127.1, 128.1, 128.4, 128.9, 129.0, 129.2, 130.5, 131.5, 137.3, 137.8, 157.8,
d
¼39.1, 42.4, 56.1, 56.2, 69.8, 115.2,
6.96e7.01 (m, 4H), 7.13e7.26 (m, 6H) 8.03 (s, 2H); 13C NMR
(100 MHz, DMSO-d6):
d
¼40.0, 56.1, 127.2, 128.9, 130.5, 137.2, 166.8;
166.9, 166.9; HRMS (ESI-TOF, m/z) calcd for
C25H25N2O3
HRMS (ESI-TOF, m/z) calcd for C18H19N2O2 (MþH)þ¼295.1441,
(MþH)þ¼401.1860, found 401.1865.
found 295.1445.
4.2.1.19. (3R,6R)-3,6-Bis(
r-(benzyloxy)benzyl)piperazine-2,5-
4.2.1.11. (3R,6R)-3,6-Dibenzylpiperazine-2,5-dione (7).27 White
dione (15). White powder; 1H NMR (400 MHz, DMSO-d6):
d
¼2.13
powder; 1H NMR (400 MHz, DMSO-d6):
d
¼2.18 (dd, J¼14.1, 6.1 Hz,
(dd, J¼13.9, 6.0 Hz, 2H), 2.47 (dd, J¼9.7, 4.7 Hz, 2H), 3.83e3.89 (m,
2H), 4.99 (s, 4H), 6.87 (d, J¼9.3 Hz, 2H), 6.89 (d, J¼9.3 Hz, 2H),
7.21e7.33 (m, 10H), 7.83 (s, 2H); 13C NMR (100 MHz, DMSO-d6):
2H), 2.52 (dd, J¼13.6, 4.9 Hz, 2H), 3.89e3.95 (m, 2H), 6.96e7.01 (m,
4H), 7.13e7.26 (m, 6H) 8.03 (s, 2H); 13C NMR (100 MHz, DMSO-d6):
d
¼40.0, 56.1, 127.2, 128.9, 130.5, 137.2, 166.8; HRMS (ESI-TOF, m/z)
d
¼39.2, 56.2, 67.7, 115.2, 128.1, 128.4, 129.0, 129.3, 131.5, 137.8, 157.8,
calcd for C18H19N2O2 (MþH)þ¼295.1441, found 295.1450.
167.0,
HRMS
(ESI-TOF,
m/z)
calcd
for
C32H31N2O4
(MþH)þ¼507.2278, found 507.2286.
4.2.1.12. (3R,6S)-3,6-Dibenzylpiperazine-2,5-dione (8).28 White
powder; 1H NMR (400 MHz, DMSO-d6):
d¼2.67 (dd, J¼14.0, 8.0 Hz,
4.2.1.20. (3S,6S)-3,6-Bis(
r-(benzyloxy)benzyl)piperazine-2,5-
2H), 2.95 (dd, J¼12.0, 4.0 Hz, 2H), 3.33 (br, 2H), 7.06e7.09 (m, 4H),
dione (16).33 White powder; 1H NMR (400 MHz, DMSO-d6):
(dd, J¼13.9, 6.0 Hz, 2H), 2.47 (dd, J¼9.7, 4.7 Hz, 2H), 3.83e3.89 (m,
2H), 4.99 (s, 4H), 6.87 (d, J¼9.3 Hz, 2H), 6.89 (d, J¼9.3 Hz, 2H),
7.21e7.33 (m, 10H), 7.83 (s, 2H); 13C NMR (100 MHz, DMSO-d6):
d
¼2.13
7.16e7.22 (m, 6H), 8.01 (s, 2H); 13C NMR (100 MHz, DMSO-d6):
d
¼32.2, 55.0, 127.0, 128.4, 130.1, 136.3, 167.3, HRMS (ESI-TOF, m/z)
calcd for C18H19N2O2 (MþH)þ¼295.1441, found 295.1452.
d
¼39.2, 56.2, 67.7, 115.2, 128.1, 128.4, 129.0, 129.3, 131.5, 137.8, 157.8,
4.2.1.13. (3S,6S)-3-Benzyl-6-isobutylpiperazine-2,5-dione
167.0;
HRMS
(ESI-TOF,
m/z)
calcd
for
C32H31N2O4
(9).29 White powder; 1H NMR (400 MHz, DMSO-d6):
d¼0.01e0.08
(MþH)þ¼507.2278, found 507.2288.
(m, 1H), 0.54 (d, J¼6.6 Hz, 3H), 0.58 (d, J¼6.6 Hz, 3H), 0.65e0.83 (m,
3H), 1.28e1.41 (m, 1H), 3.08 (dd, J¼13.6, 3.7 Hz, 1H), 3.38e3.45 (m,
1H) 4.09e4.15 (m, 1H), 7.05e7.25 (m, 5H), 8.04 (s, 1H), 8.02 (s, 1H);
4.2.1.21. (3S,6R)-3-(
r-(Benzyloxy)benzyl)-6-isopropylpiperazine-
2,5-dione (17). White powder; 1H NMR (400 MHz, DMSO-d6):
13C NMR (100 MHz, DMSO-d6):
d¼22.0, 23.4, 23.5, 39.1, 44.3, 52.9,
d
¼0.22 (d, J¼7.0 Hz, 3H), 0.60 (d, J¼7.0 Hz, 3H), 1.59e1.71 (m, 1H),
56.1, 127.4, 128.7, 131.1, 136.7, 166.8, 168.1; HRMS (ESI-TOF, m/z)
2.75 (dd, J¼14.0, 4.8 Hz,1H), 3.03 (dd, J¼14.0, 4.8 Hz,1H), 3.44e3.49
(m, 1H), 4.07e4.13 (m, 1H), 5.00 (s, 2H), 6.83 (d, J¼8.5 Hz, 2H), 7.03
(d, J¼8.5 Hz, 2H), 7.23e7.38 (m, 5H), 7.83 (s, 1H), 8.01 (s, 1H); 13C
calcd for C15H21N2O2 (MþH)þ¼261.1598, found 261.1607.
4.2.1.14. (3R,6R)-3-Isobutyl-6-phenethylpiperazine-2,5-dione
NMR (100 MHz, DMSO-d6):
d¼16.8, 18.9, 31.7, 37.6, 55.8, 59.8, 69.7,
(10). White powder; 1H NMR (400 MHz, DMSO-d6):
(m, 6H) 1.40e1.47 (m, 1H) 1.55e1.62 (m, 1H) 1.76e1.97 (m, 3H) 2.60
(t, J¼8.0 Hz, 2H), 3.74e3.76 (m, 2H) 7.13e7.18 (m, 3H), 7.22e7.26 (m,
2H), 8.18 (s, 1H), 8.25 (s, 1H); 13C NMR (100 MHz, DMSO-d6):
d
¼0.81e0.85
115.1, 128.1, 128.3, 129.0, 129.1, 131.9, 137.9, 157.9, 167.1, 167.3; HRMS
(ESI-TOF, m/z) calcd for C21H25N2O3 (MþH)þ¼353.1860, found
353.1867.
d
¼22.3, 23.4, 24.0, 35.9, 43.4, 53.0, 54.1, 126.3, 128.8, 141.7, 168.2,
4.2.1.22. (3R,6R)-3-Benzyl-6-methylpiperazine-2,5-dione
169.0; HRMS (ESI-TOF, m/z) calcd for C18H31N2 (MþH)þ¼275.2482,
(18). White powder; 1H NMR (400 MHz, DMSO-d6):
d¼0.40 (d,
found 275.1763.
J¼6.9 Hz, 3H), 2.80 (dd, J¼13.7, 4.9 Hz, 1H), 3.08 (dd, J¼13.5, 5.6 Hz,
1H), 3.53e3.60 (m, 1H), 4.10e4.15 (m, 1H), 7.07e7.15 (m, 2H),
7.14e7.26 (m, 3H), 7.97 (s, 1H), 8.07 (s, 1H); 13C NMR (100 MHz,
4.2.1.15. (3R,6R)-3,6-Diisobutylpiperazine-2,5-dione (11). White
powder; 1H NMR (400 MHz, DMSO-d6):
d
¼0.81 (d, J¼6.5 Hz, 6H),
DMSO-d6):
d¼20.4, 39.0, 50.4, 56.0, 127.3, 128.7, 131.0, 136.7, 166.5,