Use of α,ω-Dichloroketimine Building Blocks for the Construction of 1-Azabicyclo[3.1.0]hexanes, Piperidines, Pyridines, Pyrroles, and Tetrahydroindoles

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 - tetrahydroindoles

• References and Notes

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• 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), ν_max = 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).
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• 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; R_f = 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): ν_max = 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).