9
(3R,7aS)-2-phenyl-3-(o-tolyl)hexahydro-1H-pyrrolo[1,2-
c]imidazol-1-one (exo-34): 82% yield. White solid (Rf = 0.33 in
7:3 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3) δ 7.50 (d, J =
8.8 Hz, 2H), 7.32-7.25 (comp. m, 3H), 7.22 (t, J = 7.6 Hz, 1H),
7.15-7.04 (comp. m, 3H), 5.87 (s, 3H), 3.92 (dd, J = 8.8, 4.0 Hz,
1H), 3.49-3.42 (m, 1H), 2.86 (dt, J = 9.2, 7.2 Hz, 1H), 2.54 (s,
3H), 2.31-2.13 (comp. m, 2H), 1.97-1.84 (comp. m, 2H); 13C
NMR (100 MHz, CDCl3) δ 175.9, 138.2, 136.5, 135.8, 131.6,
129.1, 128.5, 126.6, 124.8, 124.3, 120.1, 80.3, 64.1, 55.8, 27.1,
25.0, 19.3; IR (film) 1700, 1594, 1500, 1379, 757 cm-1; HRMS
(ESI+) m/z calc’d for (M + H)+ [C19H20N2O + H]+: 293.1648,
found 293.1649.
124.5, 119.9, 81.2, 63.9, 54.3, 26.5, 26.1, 24.5; IR (film) 1699,
ACCEPTED MANUSCRIPT
1598, 1498, 1390, 1296 cm-1; HRMS (ESI+) m/z calc’d for (M +
H)+ [C23H22N2O + H]+: 343.1805, found 343.1812.
(3R,7aS)-3-(8-fluoronaphthalen-1-yl)-2-phenylhexahydro-
1H-pyrrolo[1,2-c]imidazol-1-one
(exo-45):
74%
yield.
Colorless oil (Rf = 0.61 in 7:3 hexanes/EtOAc). 1H NMR (400
MHz, CDCl3) δ 7.82 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 8.4 Hz,
1H), 7.63 (d, J = 8.4 Hz, 2H), 7.47 (dt, J = 7.6, 4.8 Hz, 1H), 7.40-
7.25 (comp. m, 5H), 7.09 (t, J = 7.2 Hz, 1H), 6.82 (s, 1H), 3.89
(dd, J = 9.2, 3.2 Hz, 1H), 3.66-3.64 (m, 1H), 2.97-2.87 (m, 1H),
2.33-2.23 (m, 1H), 2.21-2.10 (m, 1H), 1.98-1.81 (comp. m, 2 H);
13C NMR (100 MHz, CDCl3) δ 176.3, 159.5 (d, J = 249.8 Hz),
138.4, 137.2 (d, J = 5.9 Hz), 132.7 (d, J = 7.3 Hz), 129.2 (d, J =
2.7 Hz), 129.1, 126.3 (d, J = 4.8 Hz), 126.2 (d, J = 3.0 Hz), 125.5
(d, J = 3.7 Hz), 124.6, 123.5, 121.1 (d, J = 13.1 Hz), 119.8, 112.6
(3R,7aS)-3-(2-methoxyphenyl)-2-phenylhexahydro-1H-
pyrrolo[1,2-c]imidazol-1-one (exo-35): 95% yield. White solid
(Rf = 0.17 in 3:2 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3) δ
7.52 (d, J = 8.0 Hz, 2H), 7.30-7.23 (comp. m, 3H), 7.10-7.04
(comp. m, 2H), 6.94 (d, J = 8.4 Hz, 1H), 6.85 (t, J = 7.6 Hz, 1H),
6.11 (s, 1H), 4.03 (t, J = 6.8 Hz, 1H), 3.93 (s, 3H), 3.47 (dt, J =
9.0, 5.2 Hz, 1H), 2.87 (dt, J = 9.0, 8.4 Hz, 1H), 2.21 (q, J = 6.8
Hz, 2H), 1.93-1.84 (comp. m, 2 H); 13C NMR (100 MHz, CDCl3)
δ 175.7, 156.9, 137.9, 129.7, 129.0, 127.0, 125.8, 124.8, 120.8,
120.5, 111.3, 78.5, 64.5, 56.3, 55.7, 27.6, 25.0; IR (film) 1700,
1594, 1500, 1379, 757 cm-1; HRMS (ESI+) m/z calc’d for (M +
H)+ [C19H20N2O2 + H]+: 309.1598, found 309.1598.
(d, J = 24.1 Hz), 80.8 (d, J = 14.3 Hz), 63.7, 55.3, 26.8, 24.8; 19
F
NMR (272 MHz, CDCl3) δ -107.9; IR (film) 1699, 1597, 1498,
1388, 1308 cm-1; HRMS (ESI+) m/z calc’d for (M + H)+
[C22H19FN2O + H]+: 347.1554, found 347.1557.
(3R,7aS)-3-(5-nitronaphthalen-1-yl)-2-phenylhexahydro-
1H-pyrrolo[1,2-c]imidazol-1-one (exo-46): 58% yield. Red
foam (Rf = 0.38 in 3:2 hexanes/EtOAc). 1H NMR (400 MHz,
CDCl3) δ 8.47 (d, J = 8.4 Hz, 1H), 8.41, (d, J = 8.8 Hz, 1H), 8.19
(dd, J = 8.8, 7.2 Hz, 1H), 7.71 (t, J = 8.0 Hz, 1H), 7.57 (dd, J =
8.4, 7.6 Hz, 1H), 7.51 (d, J = 7.6 Hz, 2H), 7.40 (d, J = 7.2 Hz,
1H), 7.26 (dd, J = 8.0, 7.6 Hz, 2H), 7.09 (t, J = 7.6 Hz, 1H), 6.45
(s, 1H), 3.89 (dd, J = 9.2, 3.6 Hz, 1H), 3.67-3.60 (m, 1H), 3.00
(dt, J = 7.2, 2.4 Hz, 1H), 2.34-2.23 (m, 1H), 2.23-2.12 (m, 1H),
2.05-1.86 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 175.7, 148.1,
138.1, 134.1, 132.0, 129.3, 128.9, 128.7, 126.3, 125.3, 125.1,
124.4, 124.1, 123.5, 119.8, 79.9, 64.4, 55.3, 27.0, 25.0; IR (film)
1701, 1522, 1498, 1388, 1341 cm-1; HRMS (ESI+) m/z calc’d for
(M + H)+ [C22H19N3O3 + H]+: 374.1499, found 374.1498.
(3R,7aS)-3-(5-fluoronaphthalen-1-yl)-2-phenylhexahydro-
1H-pyrrolo[1,2-c]imidazol-1-one (exo-42): 74% yield. Beige
solid (Rf = 0.61 in 7:3 hexane/EtOAc). 1H NMR (400 MHz,
CDCl3) δ 8.12 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.60
(dt, J = 8.0, 5.6 Hz, 1H), 7.55 (d, J = 8.0 Hz, 2H), 7.43 (app. t, J
= 7.8 Hz, 1H), 7.33 (app. d, J = 7.1 Hz, 1H), 7.29-7.22 (comp m,
3H), 7.09 (t, J = 7.6 Hz, 1H), 6.44 (s, 1H), 3.94 (dd, J = 9.2, 3.6
Hz, 1H), 3.68-3.61 (m, 1H), 3.00 (td, J = 9.4, 7.0 Hz, 1H), 2.36-
2.25 (m, 1H), 2.25-2.14 (m, 1H), 2.03-1.89 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 176.0, 159.6 (d, J = 251.3 Hz), 138.4, 133.4
(d, J = 2.4 Hz), 132.4 (d, J = 4.4 Hz), 129.2, 127.0 (d, J = 8.5
Hz), 125.8 (d, J = 1.8 Hz), 125.0 (d, J = 16.2 Hz), 124.8, 123.6,
121.8 (d, J = 6.1 Hz), 119.8, 118.7 (d, J = 4.0 Hz), 110.0 (d, J =
20.0 Hz), 80.0, 64.5, 55.4, 27.1, 25.1; 19F NMR (272 MHz,
CDCl3) δ -120.8; IR (film) 1701, 1599, 1499, 1388, 1229 cm-1;
HRMS (ESI+) m/z calc’d for (M + H)+ [C22H19FN2O + H]+:
347.1554, found 347.1548.
(3R,7aS)-3-(anthracen-9-yl)-2-phenylhexahydro-1H-
pyrrolo[1,2-c]imidazol-1-one (exo-47): 79% yield. Orange
powder (Rf = 0.33 in 1:1 hexanes/EtOAc). 1H NMR (400 MHz,
CDCl3) δ 8.57 (br. s, 2H), 8.39 (s, 1H), 7.95 (d, J = 8.4 Hz, 2H),
7.57 (t, J = 7.6 Hz, 2H), 7.44 (t, J = 7.6 Hz, 2H), 7.18 (d, J = 7.6
Hz, 2H), 7.11 (s, 1H), 6.97 (t, J = 7.6 Hz, 2H), 6.85 (t, J = 7.6
Hz, 1H), 4.50 (t, J = 7.2 Hz, 1H), 3.26-3.05 (comp. m, 2H), 2.42-
2.32 (comp. m, 2H), 2.21-2.07 (m, 1H), 2.06-1.95 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 173.4, 139.5, 130.4, 129.9, 128.6,
127.1, 125.9, 124.8, 123.3, 79.2, 66.7, 55.2, 30.0, 24.9; IR (film)
1693, 1598, 1499, 1395, 1312 cm-1; HRMS (ESI+) m/z calc’d for
(M + H)+ [C26H22N2O + H]+: 379.1805, found 379.1813.
(3R,7aS)-3-(naphthalen-2-yl)-2-phenylhexahydro-1H-
pyrrolo[1,2-c]imidazol-1-one (exo-43): 64% yield. Beige solid
(Rf = 0.11 in 7:3 hexane/EtOAc). 1H NMR (400 MHz, CDCl3) δ
7.88 (d, J = 8.4 Hz, 1H), 7.85-7.75 (comp m, 2H), 7.70 (s, 1H),
7.53 (d, J = 7.6 Hz, 2H), 7.51-7.44 (comp. m, 3H), 7.27 (t, J =
7.6 Hz, 2H), 7.09 (t, J = 7.6 Hz, 1H), 5.83 (s, 1H), 4.10 (dd, J =
7.6, 6.0 Hz, 1H), 3.51-3.44 (m, 1H), 3.94 (q, J = 4.4 Hz, 1H),
2.28-2.20 (comp. m, 2H), 1.98-1.88 (comp. m, 2H); 13C NMR
(100 MHz, CDCl3) δ 175.2, 137.8, 136.9, 133.4, 133.3, 129.4,
129.1, 128.3, 127.8, 126.6, 126.5, 125.2, 125.1, 124.0, 121.2,
83.9, 64.6, 56.1, 27.7, 25.0; IR (film) 1684, 1594, 1494, 1405,
820 cm-1; HRMS (ESI+) m/z calc’d for (M + H)+ [C22H20N2O +
H]+: 329.1648, found 329.1649.
Acknowledgments
The Donors of the American Chemical Society Petroleum
Research Fund are acknowledged for support of this research.
Curtis Seizert, Tyler Miller, and Angella Greenawalt are
acknowledged for experimental contributions.
References and notes
1. For a review on SRS, see: Seebach, D.; Sting, A. R.; Hoffmann,
M. Angew. Chem., Int. Ed. Engl. 1996, 35, 2708-2748.
2. Stache, E. E.; Seizert, C. A.; Ferreira, E. M. Chem. Sci. 2012, 3,
1623-1628.
(3R,7aS)-3-(8-methylnaphthalen-1-yl)-2-phenylhexahydro-
1H-pyrrolo[1,2-c]imidazol-1-one (exo-44): 67% yield. White
solid (Rf = 0.28 in 7:3 hexanes/EtOAc). 1H NMR (400 MHz,
CDCl3) δ 7.80 (dd, J = 7.6, 1.6 Hz, 1H), 7.75 (dd, J = 7.2, 2.4 Hz,
1H), 7.51 (d, J = 8.0 Hz, 2H), 7.42-7.21 (comp. m, 6H), 7.05 (t, J
= 7.6 Hz, 1H), 6.90 (s, 1H), 3.94 (dd, J = 9.2, 2.8 Hz, 1H), 3.60
(ddd, 9.6, 6.8, 3.2 Hz, 1H), 3.14 (s, 3H), 2.84 (dt, J = 9.6, 2.0 Hz,
1H), 2.36-2.27 (m, 1H), 2.15-2.04 (m, 1H), 1.98-1.82 (comp. m,
2H); 13C NMR (100 MHz, CDCl3) δ 176.5, 138.6, 136.7, 134.2,
133.4, 131.4, 131.30, 131.25, 129.2, 128.8, 125.7, 125.0, 124.6,
3. For a review on α-quaternary proline derivatives, see: Calaza, M.
I.; Cativiela, C. Eur. J. Org. Chem. 2008, 3427-3448.
4. For select examples of syntheses and applications of α-quaternary
proline-based amino acids and derivatives, see: (a) Frebault, F.;
Simpkins, N. S.; Fenwick, A. J. Am. Chem. Soc. 2009, 131, 4214-
4215. (b) Crick, P. J.; Simpkins, N. S.; Highton, A. Org. Lett.
2011, 13, 6472-6475. (c) Su, B.; Cai, C.; Wang, Q. J. Org.
Chem. 2012, 77, 7981-7987. (d) Tong, S.-T.; Harris, P. W. R.;