F
N. Piens et al.
Letter
Synlett
Soc. Chim. Belg. 1986, 95, 567. (i) De Kimpe, N.; Moens, L. Tetra-
hedron 1990, 46, 2965. (j) Van Nguyen, T.; De Kimpe, N. Tetrahe-
dron 2000, 56, 7299. (k) Florio, S.; Troisi, L.; Capriati, V.; Suppa,
G. Eur. J. Org. Chem. 2000, 3793. (l) Concellón, J. M.; Bernad, P. L.;
Riego, E.; García-Granda, S.; Forcén-Acebal, Á. J. Org. Chem.
2001, 66, 2764. (m) Rozentsveig, G. N.; Rozentsveig, I. B.;
Levkovskaya, G. G.; Albanov, A. I.; Mirskova, A. N. Russ. J. Org.
Chem. 2003, 39, 1801. (n) Concellón, J. M.; Riego, E.; Rivero, I. A.;
Ochoa, A. J. Org. Chem. 2004, 69, 6244. (o) Van Brabandt, W.;
Dejaegher, Y.; De Kimpe, N. Pure Appl. Chem. 2005, 77, 2061.
(p) Malkov, A. V.; Stončius, S.; Kočovský, P. Angew. Chem. Int. Ed.
2007, 46, 3722. (q) Van Hende, E.; Verniest, G.; Surmont, R.; De
Kimpe, N. Org. Lett. 2007, 9, 2935. (r) D’hooghe, M.; Van Bra-
bandt, W.; Dekeukeleire, S.; Dejaegher, Y.; De Kimpe, N. Chem.
Eur. J. 2008, 14, 6336. (s) D’hooghe, M.; Buyck, C.; Contreras, J.;
De Kimpe, N. Org. Biomol. Chem. 2008, 6, 3667. (t) D’hooghe, M.;
Aelterman, W.; De Kimpe, N. Org. Biomol. Chem. 2009, 7, 135.
(u) Moens, M.; De Kimpe, N.; D’hooghe, M. J. Org. Chem. 2014,
79, 5558.
39.3, 39.4, 50.9, 75.4, 128.2, 129.8, 164.6. IR (NaCl): ν = 1645
(C=N) cm–1. MS (70 eV): m/z (%) = 163 (51), 162 (6), 159 (2), 148
(61), 146 (3), 133 (5), 132 (5), 131 (5), 122 (14), 121 (32), 120
(100), 118 (6), 106 (21), 91 (8), 81 (8), 79 (13), 77 (21), 67 (6), 65
(9), 51 (10), 43 (44).
(12) Maiti, S. N.; Singh, M. P.; Micetich, R. G. Tetrahedron Lett. 1986,
27, 1423.
(13) cis-3-Chloro-2,3-dimethyl-5-methylenepiperidine (6a)
White solid; yield 72% (1 mmol); mp 46.0–46.6 °C; Rf = 0.30
(CH2Cl2–MeOH = 96:4). 1H NMR (270 MHz, CDCl3): δ = 1.14 (3 H,
d, J = 6.3 Hz), 1.57 (3 H, s), 1.68 (1 H, s), 2.45 (1 H, AB q, J = 14.3,
1.5 Hz), 2.62 (1 H, AB d, J = 14.3, 2.0 Hz), 2.71 (1 H, q, J = 6.3 Hz),
3.22 (1 H, AB d, J = 14.3, 1.3 Hz), 3.43 (1 H, AB d, J = 14.3, 2.0 Hz),
4.74 (1 H, d, J = 1.5 Hz), 4.83 (1 H, q, J = 1.5 Hz). 13C NMR (68
MHz, CDCl3): δ = 16.7, 29.8, 49.3, 52.5, 59.9, 76.0, 110.5, 142.4.
IR (NaCl): ν = 3100–3320 (NH), νmax = 1440, 1375, 1130, 1111,
906 cm–1. MS (70 eV): m/z (%) = 159/61 (11) [M+], 124 (28), 122
(7), 108 (10), 96 (22), 83 (10), 82 (11), 81 (13), 79 (12), 77 (17),
68 (11), 67 (13), 61 (17), 59 (11), 56 (11), 55 (21), 44 (100).
(14) Pal, K.; Behnke, M. L.; Tong, L. Tetrahedron Lett. 1993, 34, 6205.
(15) (a) Schneider, M. J. Alkaloids: Chem. Biol. Perspect. 1996, 10, 155.
(b) O’Hagan, D. Nat. Prod. Rep. 2000, 17, 435. (c) Källström, S.;
Leino, R. Bioorg. Med. Chem. 2008, 16, 601. (d) Hill, M. D. Chem.
Eur. J. 2010, 16, 12052. (e) Chaubey, A.; Pandeya, S. N. Asian J.
Pharm. Clin. Res. 2011, 4, 5. (f) Haider, S.; Saify, Z. S.; Begum, N.;
Ashraf, S.; Zarreen, T.; Saeed, S. M. G. World J. Pharm. Res. 2014,
3, 987. (g) Guan, A.-Y.; Liu, C.-L.; Sun, X.-F.; Xie, Y.; Wang, M.-A.
Bioorg. Med. Chem. 2016, 24, 342.
(2) (a) Mangelinckx, S.; Boeykens, M.; De Kimpe, N. Synlett 2008,
1394. (b) Sulmon, P.; De Kimpe, N.; Schamp, N. J. Chem. Soc.,
Chem. Commun. 1985, 715. (c) Sulmon, P.; De Kimpe, N.;
Schamp, N.; Tinant, B.; Declercq, J.-P. Tetrahedron 1988, 44,
3653. (d) Sulmon, P.; De Kimpe, N.; Schamp, N. J. Org. Chem.
1988, 53, 4462. (e) Sulmon, P.; De Kimpe, N.; Schamp, N. Tetra-
hedron 1989, 45, 2937.
(3) (a) Aelterman, W.; De Kimpe, N.; Tyvorskii, V.; Kulinkovich, O. J.
Org. Chem. 2001, 66, 53. (b) Zhao, S.; Jeon, H.-B.; Nadkarni, D. V.;
Sayre, L. M. Tetrahedron 2006, 62, 6361. (c) Sastry, M. N. V.;
Mangelinckx, S.; Lucas, B.; De Kimpe, N. Synlett 2011, 2852.
(4) (a) Sulmon, P.; De Kimpe, N.; Schamp, N. Tetrahedron 1989, 45,
3907. (b) Verniest, G.; Surmont, R.; Van Hende, E.; Deweweire,
A.; Deroose, F.; Thuring, J. W.; De Kimpe, N. J. Org. Chem. 2008,
73, 5458.
(16) cis-5,6-Dimethyl-3-methylene-1-azabicyclo[3.1.0]hexane
(7a)
Colorless liquid; yield 65% (1 mmol); Rf = 0.17 (CH2Cl2–MeOH =
96:4). 1H NMR (270 MHz, C6D6): δ = 0.89 (3 H, d, J = 6.4 Hz), 1.20
(3 H, s), 1.81 (1 H, q, J = 6.4 Hz), 2.29 and 2.33 (2 H, AB, J = 17.5
Hz), 3.14 and 3.83 (2 H, AB, J = 16.8 Hz), 4.58 (1 H, quint, J = 2.3
Hz), 4.68 (1 H, quint, J = 2.3 Hz). 13C NMR (68 MHz, C6D6): δ =
(5) Chen, Z.; Zhu, J.; Xie, H.; Li, S.; Wu, Y.; Gong, Y. Org. Lett. 2010,
12, 4376.
7.6, 23.3, 36.7, 42.8, 48.2, 54.5, 103.2, 155.1. IR (NaCl): νmax
=
(6) De Kimpe, N.; Keppens, M. Tetrahedron 1996, 52, 3705.
(7) (a) De Kimpe, N.; Schamp, N. J. Org. Chem. 1975, 40, 3749. (b) De
Kimpe, N.; Sulmon, P.; Moens, L.; Schamp, N.; Declercq, J. P.;
Van Meerssche, M. J. Org. Chem. 1986, 51, 3839.
(8) De Kimpe, N.; Verhé, R.; De Buyck, L.; Moens, L.; Schamp, N. Syn-
thesis 1982, 43.
(9) (a) De Kimpe, N.; Sulmon, P.; Schamp, N. Angew. Chem., Int. Ed.
Engl. 1985, 24, 881. (b) Mangelinckx, S.; Giubellina, N.; De
Kimpe, N. Chem. Rev. 2004, 104, 2353.
(10) N-(2-Chloro-4-chloromethyl-1,2-dimethylpent-4-
enylidene)isopropylamine (2a)
2919, 1447, 1376, 1168, 1086, 879 cm–1. MS (70 eV): m/z (%) =
123 (11) [M+], 122 (8), 108 (5), 107 (4), 106 (4), 93 (3), 82 (40),
81 (12), 77 (6), 67 (100), 55 (10), 54 (35), 53 (14), 51 (5).
(17) (a) Coleman, R. S.; Richardson, T. E.; Kong, J.-S. Chem. Heterocycl.
Compd. 1998, 34, 1382. (b) Foulke-Abel, J.; Agbo, H.; Zhang, H.;
Mori, S.; Watanabe, C. M. H. Nat. Prod. Rep. 2011, 28, 693.
(c) Nepal, K. K.; Lee, R. P.; Rezenom, Y. H.; Watanabe, C. M. H.
Biochemistry 2015, 54, 4415.
(18) (a) Le Quesne, P. W.; Dong, Y.; Blythe, T. A. Alkaloids: Chem. Biol.
Perspect. 1999, 13, 237. (b) Abbaspour Tehrani, K.; Borremans,
D.; De Kimpe, N. Tetrahedron 1999, 55, 4133. (c) Gupton, J. T.
Top. Heterocycl. Chem. 2006, 2, 53. (d) Shrinivas, D. J.; Uttam, A.
M.; Venkatrao, H. K.; Tejraj, M. A. Curr. Org. Chem. 2013, 17,
2279. (e) Bhardwaj, V.; Gumber, D.; Abbot, V.; Dhiman, S.;
Sharma, P. RSC Adv. 2015, 5, 15233. (f) Domagala, A.; Jarosz, T.;
Lapkowski, M. Eur. J. Med. Chem. 2015, 100, 176. (g) Gholap, S. S.
Eur. J. Med. Chem. 2016, 110, 13.
Yellow liquid; yield 81% (41 mmol). 1H NMR (270 MHz, CDCl3):
δ = 1.08 (3 H, d, J = 6.3 Hz), 1.10 (3 H, d, J = 6.3 Hz), 1.69 (3 H, s),
2.03 (3 H, s), 2.94 (2 H, s), 3.65 (1 H, sept, J = 6.3 Hz), 4.06 and
4.14 (2 H, AB, J = 11.9 Hz), 5.08 (1 H, d, J = 0.7 Hz), 5.31 (1 H, d, J
= 0.7 Hz). 13C NMR (68 MHz, C6D6): δ = 13.1, 22.9, 23.3, 28.0,
44.6, 48.8, 51.0, 75.4, 119.7, 141.6, 165.2. IR (NaCl): ν = 1647
(C=N) cm–1. MS (70 eV): m/z (%) = 200/2 (76) [M+ – Cl], 186 (9),
164 (18), 158 (19), 122 (20), 121 (9), 108 (18), 107 (14), 84 (61),
81 (13), 79 (15), 77 (11), 58 (12), 53 (11), 49 (19), 42 (100).
(11) (4Z)-N-(2,6-Dichloro-1,2-dimethylhex-4-enylidene)isopro-
pylamine (3a)
(19) Krief, A. Tetrahedron 1980, 36, 2531.
(20) 3-Chloro-1-isopropyl-2-methyl-5-vinyl-1H-pyrrole (21a)
Yellow liquid; yield 85% (2 mmol). 1H NMR (270 MHz, CDCl3): δ
= 1.51 (6 H, d, J = 7.1 Hz), 2.29 (3 H, s), 4.49 (1 H, sept, J = 7.1 Hz),
5.04 (1 H, dd, J = 10.9, 1.7 Hz), 5.44 (1 H, dd, J = 17.1, 1.7 Hz),
6.30 (1 H, s), 6.70 (1 H, dd, J = 17.1, 10.9 Hz). 13C NMR (68 MHz,
CDCl3): δ = 10.8, 22.6, 48.1, 105.7, 110.1, 112.0, 124.9, 130.0,
126.5. IR (NaCl): ν = 1616 (C=C), νmax = 1440, 1315, 1279, 1180
cm–1. MS (70 eV): m/z (%) = 183/5 (47) [M+], 169/71 (5), 168/70
(35), 144 (10), 143 (19), 142 (43), 141 (56), 140 (100), 132 (6),
Yellow liquid; yield 67% (34 mmol). 1H NMR (270 MHz, C6D6): δ
= 1.00 (3 H, d, J = 5.9 Hz), 1.01 (3 H, d, J = 5.9 Hz), 1.54 (3 H, s),
1.66 (3 H, s), 2.63 (1 H, AB d, J = 14.7, 6.3 Hz), 2.75 (1 H, AB d, J =
14.7, 5.8 Hz), 3.34 (1 H, sept, J = 5.9 Hz), 3.66–3.78 (2 H, m),
5.48–5.63 (2 H, m). 13C NMR (68 MHz, C6D6): δ = 12.8, 23.3, 28.0,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–G