RSS-Feed abonnieren
Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.
https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000083.xml
PDF herunterladen
Synlett 2017; 28(02): 207-213
DOI: 10.1055/s-0036-1588882
DOI: 10.1055/s-0036-1588882
letter
Use of α,ω-Dichloroketimine Building Blocks for the Construction of 1-Azabicyclo[3.1.0]hexanes, Piperidines, Pyridines, Pyrroles, and Tetrahydroindoles
Weitere Informationen
Publikationsverlauf
Received: 19. August 2016
Accepted after revision: 24. August 2016
Publikationsdatum:
13. September 2016 (online)
Abstract
A variety of different N-[2-chloro-4-(chloromethyl)pent-4-enylidene]amines and N-(2,6-dichlorohex-4-enylidene)amines was prepared for the first time, and their reactivity as eligible building blocks for the synthesis of biologically relevant nitrogen-containing heterocyclic compounds was studied. In this way, a convenient entry into functionalized 1-azabicyclo[3.1.0]hexanes, piperidines, pyridines, pyrroles, and tetrahydroindoles was developed, pointing to the broad synthetic flexibility of these dichlorinated imine substrates.
Key words
α,ω-dichloroketimines - 1-azabicyclo[3.1.0]hexanes - piperidines - pyridines - pyrroles - tetrahydroindolesSupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0036-1588882.
- Supporting Information
-
References and Notes
- 1a De Kimpe N, Verhé R, De Buyck L, Schamp N. Synth. Commun. 1975; 5: 269
- 1b De Kimpe N, Schamp N, Verhé R. Synth. Commun. 1975; 5: 403
- 1c De Kimpe N, Schamp N. Org. Prep. Proced. Int. 1979; 11: 115
- 1d De Kimpe N, Verhé R, De Buyck L, Schamp N. J. Org. Chem. 1980; 45: 5319
- 1e De Kimpe N, Verhé R, De Buyck L, Schamp N. J. Org. Chem. 1981; 46: 2079
- 1f De Kimpe N, Moens L, Verhé R, De Buyck L, Schamp N. J. Chem. Soc., Chem. Commun. 1982; 19
- 1g De Kimpe N, Sulmon P, Verhé R, De Buyck L, Schamp N. J. Org. Chem. 1983; 48: 4320
- 1h De Kimpe N, Sulmon P, Schamp N. Bull. Soc. Chim. Belg. 1986; 95: 567
- 1i De Kimpe N, Moens L. Tetrahedron 1990; 46: 2965
- 1j Van Nguyen T, De Kimpe N. Tetrahedron 2000; 56: 7299
- 1k Florio S, Troisi L, Capriati V, Suppa G. Eur. J. Org. Chem. 2000; 3793
- 1l Concellón JM, Bernad PL, Riego E, García-Granda S, Forcén-Acebal Á. J. Org. Chem. 2001; 66: 2764
- 1m Rozentsveig GN, Rozentsveig IB, Levkovskaya GG, Albanov AI, Mirskova AN. Russ. J. Org. Chem. 2003; 39: 1801
- 1n Concellón JM, Riego E, Rivero IA, Ochoa A. J. Org. Chem. 2004; 69: 6244
- 1o Van Brabandt W, Dejaegher Y, De Kimpe N. Pure Appl. Chem. 2005; 77: 2061
- 1p Malkov AV, Stončius S, Kočovský P. Angew. Chem. Int. Ed. 2007; 46: 3722
- 1q Van Hende E, Verniest G, Surmont R, De Kimpe N. Org. Lett. 2007; 9: 2935
- 1r D’hooghe M, Van Brabandt W, Dekeukeleire S, Dejaegher Y, De Kimpe N. Chem. Eur. J. 2008; 14: 6336
- 1s D’hooghe M, Buyck C, Contreras J, De Kimpe N. Org. Biomol. Chem. 2008; 6: 3667
- 1t D’hooghe M, Aelterman W, De Kimpe N. Org. Biomol. Chem. 2009; 7: 135
- 1u Moens M, De Kimpe N, D’hooghe M. J. Org. Chem. 2014; 79: 5558
- 2a Mangelinckx S, Boeykens M, De Kimpe N. Synlett 2008; 1394
- 2b Sulmon P, De Kimpe N, Schamp N. J. Chem. Soc., Chem. Commun. 1985; 715
- 2c Sulmon P, De Kimpe N, Schamp N, Tinant B, Declercq J.-P. Tetrahedron 1988; 44: 3653
- 2d Sulmon P, De Kimpe N, Schamp N. J. Org. Chem. 1988; 53: 4462
- 2e Sulmon P, De Kimpe N, Schamp N. Tetrahedron 1989; 45: 2937
- 3a Aelterman W, De Kimpe N, Tyvorskii V, Kulinkovich O. J. Org. Chem. 2001; 66: 53
- 3b Zhao S, Jeon H.-B, Nadkarni DV, Sayre LM. Tetrahedron 2006; 62: 6361
- 3c Sastry MN. V, Mangelinckx S, Lucas B, De Kimpe N. Synlett 2011; 2852
- 4a Sulmon P, De Kimpe N, Schamp N. Tetrahedron 1989; 45: 3907
- 4b Verniest G, Surmont R, Van Hende E, Deweweire A, Deroose F, Thuring JW, De Kimpe N. J. Org. Chem. 2008; 73: 5458
- 5 Chen Z, Zhu J, Xie H, Li S, Wu Y, Gong Y. Org. Lett. 2010; 12: 4376
MissingFormLabel
- 6 De Kimpe N, Keppens M. Tetrahedron 1996; 52: 3705
- 7a De Kimpe N, Schamp N. J. Org. Chem. 1975; 40: 3749
- 7b De Kimpe N, Sulmon P, Moens L, Schamp N, Declercq JP, Van Meerssche M. J. Org. Chem. 1986; 51: 3839
- 8 De Kimpe N, Verhé R, De Buyck L, Moens L, Schamp N. Synthesis 1982; 43
- 9a De Kimpe N, Sulmon P, Schamp N. Angew. Chem., Int. Ed. Engl. 1985; 24: 881
- 9b 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) 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)isopropylamine (3a) 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, 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 SN, Singh MP, Micetich RG. 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 ML, Tong L. Tetrahedron Lett. 1993; 34: 6205
- 15a Schneider MJ. Alkaloids: Chem. Biol. Perspect. 1996; 10: 155
- 15b O’Hagan D. Nat. Prod. Rep. 2000; 17: 435
- 15c Källström S, Leino R. Bioorg. Med. Chem. 2008; 16: 601
- 15d Hill MD. Chem. Eur. J. 2010; 16: 12052
- 15e Chaubey A, Pandeya SN. Asian J. Pharm. Clin. Res. 2011; 4: 5
- 15f Haider S, Saify ZS, Begum N, Ashraf S, Zarreen T, Saeed SM. G. World J. Pharm. Res. 2014; 3: 987
- 15g Guan A.-Y, Liu C.-L, Sun X.-F, Xie Y, Wang M.-A. Bioorg. Med. Chem. 2016; 24: 342
- 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 = 7.6, 23.3, 36.7, 42.8, 48.2, 54.5, 103.2, 155.1. IR (NaCl): νmax = 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).
- 17a Coleman RS, Richardson TE, Kong J.-S. Chem. Heterocycl. Compd. 1998; 34: 1382
- 17b Foulke-Abel J, Agbo H, Zhang H, Mori S, Watanabe CM. H. Nat. Prod. Rep. 2011; 28: 693
- 17c Nepal KK, Lee RP, Rezenom YH, Watanabe CM. H. Biochemistry 2015; 54: 4415
- 18a Le Quesne PW, Dong Y, Blythe TA. Alkaloids: Chem. Biol. Perspect. 1999; 13: 237
- 18b Abbaspour Tehrani K, Borremans D, De Kimpe N. Tetrahedron 1999; 55: 4133
- 18c Gupton JT. Top. Heterocycl. Chem. 2006; 2: 53
- 18d Shrinivas DJ, Uttam AM, Venkatrao HK, Tejraj MA. Curr. Org. Chem. 2013; 17: 2279
- 18e Bhardwaj V, Gumber D, Abbot V, Dhiman S, Sharma P. RSC Adv. 2015; 5: 15233
- 18f Domagala A, Jarosz T, Lapkowski M. Eur. J. Med. Chem. 2015; 100: 176
- 18g Gholap SS. Eur. J. Med. Chem. 2016; 110: 13
- 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), 107 (5), 106 (40), 105 (6), 104 (6), 91 (5), 79 (6), 78 (6), 77 (17), 73 (6), 66 (5), 63 (8), 54 (10), 53 (6), 52 (14), 51 (14), 43 (36), 42 (11), 41 (25).
- 21a Nakano H, Umio S, Kariyone K, Tanaka K, Kishimoto T, Noguchi H, Ueda I, Nakamura H, Morimoto T. Tetrahedron Lett. 1966; 7: 737
- 21b Birchall GR, Hughes CG, Rees AH. Tetrahedron Lett. 1970; 11: 4879
- 21c Hayakawa Y, Kawakami K, Seto H, Furihata K. Tetrahedron Lett. 1992; 33: 2701
- 21d De Kimpe N, Abbaspour Tehrani K, Stevens C, De Cooman P. Tetrahedron 1997; 53: 3693
- 22 Hosmane RS, Hiremath SP, Schneller SW. J. Chem. Soc., Perkin Trans. 1 1973; 2450
- 23a Jones RA, Marriott MT. P, Rosenthal WP, Sepulveda-Arques J. J. Org. Chem. 1980; 45: 4515
- 23b Noland WE, Lee CK, Bae SK, Chung BY, Hahn CS, Kim KJ. J. Org. Chem. 1983; 48: 2488
- 23c Gonzalez-Rosende E, Jones RA, Sepulveda-Arques J, Zaballos-Garcia E. Synth. Commun. 1988; 18: 1669
- 23d Domingo LR, Teresa Picher M, Andrés J, Moliner V, Safont VS. Tetrahedron 1996; 52: 10693
- 23e Noland WE, Lanzatella NP, Venkatraman L, Anderson NF, Gullickson GC. J. Heterocycl. Chem. 2009; 46: 1154
- 24 cis-1-Chloro-3-isopropyl-2-phenyl-4,5,5a,11a-tetrahydro-3H-naphtho[2,3-e]indole-6,11-dione (22a) Light-brown solid; yield 72% (2 mmol); mp 197.7–198.4 °C; Rf = 0.24 (hexane–EtOAc = 85:15). 1H NMR (270 MHz, CDCl3): δ = 1.34 (3 H, d, J = 6.9 Hz), 1.37 (3 H, d, J = 6.9 Hz), 1.93–2.37 (2 H, m), 2.71–3.04 (2 H, m), 3.33 (1 H, ddd, J = 11.7, 5.6, 2.8 Hz), 4.32 (1 H, d, J = 5.6 Hz), 4.36 (1 H, sept, J = 6.9 Hz), 7.31–7.48 and 7.71–7.80 and 8.04–8.17 (9 H, m). 13C NMR (68 MHz, CDCl3): δ = 22.4, 22.6, 23.8, 26.6, 46.5, 48.9, 49.0, 109.8, 112.4, 126.4, 127.0, 127.2, 127.9, 128.3, 129.7, 131.1, 131.4, 133.6, 134.1, 134.6, 135.7, 196.0, 198.8. IR (KBr): νmax = 1667, 1587, 1351, 1286, 1249, 1213 cm–1. MS (70 eV): m/z (%) = 403/5 (100) [M+], 389/91 (7), 388/90 (20), 368 (29), 360 (6), 346 (11), 326 (13), 324 (12), 317 (6), 298 (7), 280 (9), 270 (8), 245 (5), 228 (15), 203 (11), 194 (11), 193 (34), 165 (13), 152 (6), 133 (36), 125 (6), 105 (27), 104 (23), 89 (8), 77 (20), 76 (18), 57 (15), 43 (32).