(3RS,4RS,5RS)-3-(2,2-Dimethylpropyl)-4-(iodomethyl)-1-methoxy-
3-methyl-5-phenyl-2-pyrrolidinone (trans-24). A white solid. IR
1.2 Hz), 4.85 (2H, s), 4.19 (2H, br d, J = 5.8 Hz), 2.62 (1H, m),
1.04 (6H, d, J = 6.7 Hz). 13C NMR (CDCl3) δ 167.2, 148.5,
134.4, 131.5, 129.3, 128.9, 128.6, 118.9, 89.4, 76.7, 51.4, 35.7,
20.9. MS (EI+) m/z 385 (M+, 2), 91 (100). HRMS (EI+) calcd
for C16H20INO2 (M+) 285.0539, found 385.0558.
1
(CHCl3) 1716 cm−1. H NMR (CDCl3) δ 7.47–7.39 (5H, m),
4.22 (1H, d, J = 9.1 Hz), 3.57 (3H, s), 3.17 (1H, dd, J = 10.4,
6.7 Hz), 3.12–3.01 (2H, m), 1.94 (1H, d, J = 15.0 Hz), 1.68
(1H, d, J = 15.0 Hz), 1.12 (3H, s), 1.10 (9H, s). 13C NMR
(CDCl3) δ 176.4, 137.6, 129.1, 128.9, 128.4, 66.8, 62.8, 47.2,
45.8, 45.5, 31.7, 31.4, 20.2, −2.4. MS (EI+) m/z 415 (M+, 3),
136 (100). HRMS (EI+) calcd for C18H26INO2 (M+) 415.1008,
found 415.1016. HPLC (Chiralcel AD-H, hexane–2-propanol =
95 : 5, 0.5 mL min−1, 254 nm) tr (racemic) = 21.0 and 22.2 min.
4-(Iodomethyl)-3-methyl-3-(2-methylpropyl)-1-(phenylmethoxy)-
1
2-piperidinone (15). A colorless oil. IR (CHCl3) 1650 cm−1. H
NMR (CDCl3) δ 7.46–7.41 (2H, m), 7.39–7.33 (3H, m), 4.97
(1H, d, J = 10.4 Hz), 4.86 (1H, d, J = 10.4 Hz), 3.48–3.37 (3H,
m), 2.87 (1H, t, J = 10.1 Hz), 2.25 (1H, m), 1.92–1.79 (3H, m),
1.53 (1H, dd, J = 14.0, 5.2 Hz), 1.36 (3H, s), 1.28 (1H, dd, J =
14.0, 6.1 Hz), 0.96 (3H, d, J = 6.7 Hz), 0.92 (3H, d, J = 6.5 Hz).
MS (CI+) m/z 416 (M + H+, 0.1), 91 (100). HRMS (CI+) calcd
for C18H27INO2 (M + H+) 416.1085, found 416.1071.
(3S,4R,5R)-5-Ethenyl-4-(iodomethyl)-1-methoxy-3-methyl-3-(2-
methylpropyl)-2-pyrrolidinone (25). A colorless oil. IR (CHCl3)
1
1705 cm−1. H NMR (CDCl3) δ 7.45–7.33 (5H, m), 5.56 (1H,
m), 5.35 (1H, d, J = 9.8 Hz), 5.32 (1H, d, J = 16.8 Hz), 5.04
(1H, d, J = 10.4 Hz), 4.90 (1H, d, J = 10.4 Hz), 3.58 (1H, t, J =
8.5 Hz), 3.15–3.03 (2H, m), 2.16 (1H, m), 1.90 (1H, m), 1.48
(1H, dd, J = 14.3, 3.6 Hz), 1.40 (3H, s), 1.35 (1H, dd, J = 14.3,
7.4 Hz), 0.97 (3H, d, J = 6.4 Hz), 0.92 (3H, d, J = 6.7 Hz). 13C
NMR (CDCl3) δ 174.1, 135.8, 135.1, 129.7, 129.0, 128.5,
121.7, 77.6, 66.1, 51.7, 44.3, 41.5, 29.7, 25.4, 24.5, 24.3, 24.2.
MS (FAB+) m/z 428 (M + H+, 32), 91 (100). HRMS (FAB+)
calcd for C19H27INO2 (M + H+) 428.1087, found 428.1078.
HPLC (Chiralcel AD-H, hexane–2-propanol = 95 : /5, 0.5 mL
min−1, 254 nm) tr (major) = 18.3 min, tr (minor) = 21.4 min. A
sample of 53% ee by HPLC analysis gave [α]2D5 −10.7 (c 0.4,
CHCl3).
(3S,4R,5R)-4-(Iodomethyl)-1-methoxy-3-methyl-3-(2-methylpro-
pyl)-5-phenyl-2-pyrrolidinone (cis-21). A colorless oil. IR
1
(CHCl3) 1707 cm−1. H NMR (CDCl3) δ 7.44–7.36 (5H, m),
4.31 (1H, d, J = 9.0 Hz), 3.60 (3H, s), 3.23 (1H, dd, J = 11.0,
9.5 Hz), 3.11 (1H, dd, J = 11.0, 5.5 Hz), 2.48 (1H, m), 1.99 (1H,
m), 1.62 (1H, dd, J = 14.5, 4.0 Hz), 1.48 (1H, dd, J = 14.5, 7.5
Hz), 1.46 (3H, s), 1.00 (3H, d, J = 6.5 Hz), 0.96 (3H, d, J = 6.5
Hz). 13C NMR (CDCl3) δ 174.6, 137.3, 129.0, 128.8, 128.0,
66.2, 63.0, 54.0, 44.6, 41.8, 25.5, 24.8, 24.3, 24.2, 21.5. MS
(EI+) m/z 401 (M+, 2), 378 (100). HRMS (EI+) calcd for
C17H24INO2 (M+) 401.0852, found 401.0871. HPLC (Chiralcel
AD-H, hexane–2-propanol = 95 : 5, 0.5 mL min−1, 254 nm) tr
(major) = 16.1 min, tr (minor) = 17.8 min. A sample of 99% ee
by HPLC analysis gave [α]3D1 + 29.0 (c 1.0, CHCl3).
Acknowledgements
This work was supported in part by Grant-in-Aid for Scientific
Research (C) (H.M.) from Japan Society for the Promotion of
Science.
(3R,4R,5R)-4-(Iodomethyl)-1-methoxy-3-methyl-3-(2-methylpro-
pyl)-5-phenyl-2-pyrrolidinone (trans-22). A colorless oil. IR
1
(CHCl3) 1714 cm−1. H NMR (CDCl3) δ 7.46–7.38 (5H, m),
4.13 (1H, d, J = 9.5 Hz), 3.57 (3H, s), 3.11–3.06 (2H, m), 2.74
(1H, m), 1.92 (1H, m), 1.83 (1H, dd, J = 14.5, 3.5 Hz), 1.73
(1H, dd, J = 14.5, 10.0 Hz), 1.16 (3H, s), 1.02 (3H, d, J = 6.5
Hz), 0.99 (3H, d, J = 6.5 Hz). 13C NMR (CDCl3) δ 176.7,
137.6, 129.3, 129.2, 128.2, 66.4, 63.0, 46.0, 45.0, 44.3, 24.9,
24.7, 21.8, 19.2. One carbon peak was missing due to overlap-
ping. MS (EI+) m/z 401 (M+, 1), 345 (100). HRMS (EI+) calcd
for C17H24INO2 (M+) 401.0852, found 401.0869. HPLC (Chiral-
cel AD-H, hexane–2-propanol = 95 : 5, 0.5 mL min−1, 254 nm)
tr (minor) = 11.7 min, tr (major) = 15.0 min. A sample of 95%
ee by HPLC analysis gave [α]3D1 + 28.9 (c 1.2, CHCl3).
Notes and references
1 For general information details for radical reactions, see: (a) A. G. Fallis
and I. M. Brinza, Tetrahedron, 1997, 53, 17543; (b) P. Renaud and
M. Gerster, Angew. Chem., Int. Ed., 1998, 37, 2562; (c) M. P. Sibi and N.
A. Porter, Acc. Chem. Res., 1999, 32, 163; (d) T. Naito, Heterocycles,
1999, 50, 505; (e) Radicals in Organic Synthesis, ed. P. Renaud and
M. P. Sibi, Wiley-VCH, Weinheim, 2001, vols. 1 and 2; (f) G. Bar and A.
F. Parsons, Chem. Soc. Rev., 2003, 32, 251; (g) M. P. Sibi, S. Manyem
and J. Zimmerman, Chem. Rev., 2003, 103, 3263; (h) M. Tojino and
I. Ryu, Multicompon. React., 2005, 169; (i) G. S. C. Srikanth and S.
L. Castle, Tetrahedron, 2005, 61, 10377; ( j) H. C. Guo and J. A. Ma,
Angew. Chem., Int. Ed., 2006, 4, 354; (k) J. Zimmerman and M. P. Sibi,
Top. Curr. Chem., 2006, 263, 107; (l) E. Godineau and Y. Landais,
Chem.–Eur. J., 2009, 15, 3044; (m) G. J. Rowlands, Tetrahedron, 2009,
65, 8603; (n) G. J. Rowlands, Tetrahedron, 2010, 66, 1593; (o) Y.-
H. Yang and M. P. Sibi, Encyclopedia of Radicals in Chemistry, Biology
and Materials, ed. C. Chatgilialoglu and A. Studer, Wiley, Weinheim,
2012, vol. 2, p. 655.
2 (a) H. Miyabe and Y. Takemoto, Chem.–Eur. J., 2007, 13, 7280;
(b) E. Yoshioka, S. Kohtani and H. Miyabe, Heterocycles, 2009, 79, 229.
3 M. P. Sibi and J. Ji, J. Am. Chem. Soc., 1996, 118, 3063.
4 (a) P. Renaud, T. Bourquard, M. Gerster and N. Moufid, Angew. Chem.,
Int. Ed. Engl., 1994, 33, 1601; (b) M. P. Sibi and J. Ji, Angew. Chem., Int.
Ed. Engl., 1996, 35, 190.
5 (a) T. Ooi, Y. Hokke and K. Maruoka, Angew. Chem., Int. Ed. Engl.,
1997, 36, 1181; (b) T. Ooi, Y. Hokke, E. Tayama and K. Maruoka, Tetra-
hedron, 2001, 57, 135.
6 (a) O. Corminboeuf and P. Renaud, Org. Lett., 2002, 4, 1731;
(b) O. Corminboeuf and P. Renaud, Org. Lett., 2002, 4, 1735.
(3S,4R,5R)-3-(2,2-Dimethylpropyl)-4-(iodomethyl)-1-methoxy-
3-methyl-5-phenyl-2-pyrrolidinone (cis-23). A white solid. IR
1
(CHCl3) 1708 cm−1. H NMR (CDCl3) δ 7.44–7.33 (5H, m),
4.41 (1H, d, J = 8.9 Hz), 3.60 (3H, s), 3.26 (1H, dd, J = 10.7,
8.8 Hz), 3.07 (1H, dd, J = 10.7, 5.8 Hz), 2.37 (1H, m), 1.62
(1H, d, J = 14.4 Hz), 1.55 (3H, s), 1.50 (1H, d, J = 14.4 Hz),
1.08 (9H, s). 13C NMR (CDCl3) δ 173.6, 136.6, 129.0, 128.8,
128.2, 64.8, 62.5, 57.2, 45.0, 44.7, 31.5, 31.2, 24.7, −3.2. MS
(EI+) m/z 415 (M+, 5), 136 (100). HRMS (EI+) calcd for
C18H26INO2 (M+) 415.1008, found 415.0999. HPLC (Chiralcel
AD-H, hexane–2-propanol = 95 : 5, 0.5 mL min−1, 254 nm) tr
(major) = 16.8 min, tr (minor) = 21.0 min. A sample of 99% ee
by HPLC analysis gave [α]2D8 + 20.1 (c 1.6, CHCl3).
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 3519–3530 | 3529