Niobium Pentachloride-mediated Nucleophilic Additions to Cyclic N-Acyliminium Ions

Abstract

Niobium chloride promoted the nucleophilic addition of allyltrimethylsilane, ethyl acetoacetate, indole and the silyl enol ether derived from acetone to cyclic N-acyliminium ions. The products were obtained in good yields.

N-acyliminium ions - niobium pentachloride - nucleophilic additions

References

1 Speckamp WN. Moolenaar NJ. Tetrahedron  2000,  56:  3827 

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8

Typical Experimental Procedure: To a NbCl₅ (0.6 mmol) suspension in CH₂Cl₂ (3 mL) at 0 °C, under an argon atmosphere, was added substrate 1 or 2 (1.0 mmol), diluted in CH₂Cl₂ (2 mL). After 20 min, the nucleophile (2.0 mmol) was added. After 2 h, the reaction was quenched with sat. NaHCO₃ (4 mL), extracted with CH₂Cl₂ (2 × 10 mL), dried with Na₂SO₄ and concentrated at reduced pressure to furnish the crude products 9-15, which were purified by silica gel chromatography (10% MeOH in EtOAc).

9

Selected spectroscopic data for compounds 9-15:
Compound 9: ¹H NMR (300 MHz, CDCl₃): δ = 1.75-1.80 (m, 2 H, -CH₂-CH ₂ -CH), 2.10-2.20 (m, 2 H, -CH-CH ₂ -CH=CH₂), 2.75-2.79 [m, 2 H, -C(O)-CH ₂ -CH₂], 2.78 (s, 3 H, N-CH ₃ ), 3.51-3.59 (m, 1 H, -CH-NCH₃), 5.08-5.16 (m, 2 H, -CH=CH ₂ ), 5.60-5.80 (m, 1 H, -CH=CH₂). ¹³C NMR (75 MHz, CDCl₃): δ = 23.4 [-C(O)-CH₂-CH₂-CH], 28.0 (N-CH₃), 30.1 [-C(O)-CH₂-CH₂], 37.6 (CH-CH₂-CH=CH₂), 59.5 (N-CH-CH₂-), 119.1 (-CH=CH ₂ ), 132.8 (-CH=CH₂), 175.5 (C=O).
Compound 10: ¹H NMR (300 MHz, CDCl₃): δ = 1.35-1.70 (m, 2 H, CH-CH ₂ -CH₂), 1.90-2.10 [m, 2 H, CH-CH ₂ -C(O)], 2.05 [s, 3 H, C(O)CH ₃ ], 2.30-2.70 [m, 2 H, -C(O)-CH ₂ -CH₂], 2.60 (s, 3 H, N-CH ₃ ), 3.50-3.80 (m, 1 H, -CH-NCH₃).
Compound 11: ¹H NMR (300 MHz, CDCl₃): δ = 1.28 (t, major isomer, -O-CH₂-CH ₃ , J = 7.0 Hz), 1.32 (t, minor isomer, -O-CH₂-CH ₃ , J = 8.0 Hz), 1.90-2.10 (m, 2 H, CH₂-CH ₂ -CH), 2.26 [s, minor isomer, -C(O)-CH ₃ ] 2.28-2.36 [m, 2 H, -C(O)CH ₂ -CH ₂ ], 2.29 [s, major isomer, -C(O)-CH ₃ ], 2.79 (s, minor isomer, -NCH ₃ ), 2.80 (s, major isomer,
-NCH ₃ ), 3.72 [d, minor isomer, -C(O)-CH-C(O), J = 2.5 Hz), 3.82 [d, major isomer, -C(O)-CH-C(O), J = 3.0 Hz], 4.18-4.28 (m, 2 H, -O-CH ₂ -CH₃). ¹³C NMR (75 MHz, CDCl₃): δ = 14.0 [C(O)-OCH₂-CH₃], 22.7 [-C(O)-CH₂-CH₂-CH], 28.4 (N-CH₃), 29.4 [-C(O)-CH₂-CH₂], 29.9 [C(O)-CH₃], 58.9 [C(O)-CH-C(O)], 60.7 (-NCH), 62.3
(O-CH ₂), 167.6 [-C(O)-O-CH₂], 175.3 [C(O)-NCH₃], 201.0 [-C(O)-CH₃].
Compound 12: ¹H NMR (300 MHz, CDCl₃): δ = 2.13-2.69 [m, 4 H, C(O)-CH ₂ -CH₂- and C(O)-CH₂-CH ₂ -], 2.93 (s, 3 H, N-CH ₃ ), 4.90 (t, 1 H, -CH-NCH₃, J = 6.9 Hz), 7.13 (ddd, 1 H, aromatic, J = 1.1, 7.0, 8.0 Hz), 7.22 (ddd, 1 H, aromatic, J = 1.2, 7.3, 8.4 Hz), 7.44 (d, 1 H, aromatic, J = 8.0 Hz), 7.54 (d, 1 H, aromatic, J = 7.8 Hz), 9.10 (br s, 1 H, NH). ¹³C NMR (75 MHz, CDCl₃): δ = 27.1 [-C(O)-CH₂-CH₂-CH], 28.1 (N-CH₃), 29.8 [-C(O)-CH₂-CH₂], 58.1 (-CH-NCH₃), 111.9 (CH, aromatic), 115.2 (C ₀ , aromatic), 118.8 (CH, aromatic), 120.0 (CH, aromatic), 122.5 (CH, aromatic), 122.8 (CH, aromatic), 125.4 (C ₀ , aromatic), 137.2 (HN-C-CH), 175.4 (N-C=O).
Compound 13: ¹H NMR (300 MHz, CDCl₃): δ = 1.60-1.87 (m, 4 H, CH₂-CH ₂-CH ₂ -CH), 2.14-2.50 [m, 4 H, -C(O)-CH ₂ -CH₂ and -CH ₂ -CH=CH₂], 2.91 (s, 3 H, N-CH ₃), 3.30-3.36 (m, 1 H, CH-NCH₃), 5.04-5.13 (m, 2 H, -CH=CH ₂ ), 5.56-5.77 (m, 1 H, -CH=CH₂). ¹³C NMR (75 MHz, CDCl₃): δ = 5.7 (CH₂-CH ₂ -CH₂), 14.5 (CH₂-CH₂-CH), 20.1 [-C(O)-CH ₂ -CH₂], 21.5 (N-CH₃), 25.3 (CH₂-CH=CH₂), 46.6 (N-CH-CH₂-), 106.4 (CH=CH ₂ ), 122.0 (-CH=CH₂), 158.7 (C=O).
Compound 14: ¹H NMR (300 MHz, CDCl₃): δ = 1.60-1.97 (m, 4 H, CH₂-CH ₂ -CH ₂ -CH), 2.17 [s, 3 H, C(O)-CH ₃ ], 2.34-2.40 [m, 2 H, C(O)-CH ₂ -CH₂], 2.68-2.76 [m, 2 H, CH-CH ₂ -C(O)], 2.87 (s, 3 H, N-CH ₃ ), 3.80-3.94 (m, 1 H, CH-NCH₃). ¹³C NMR (75 MHz, CDCl₃): δ = 5.6 (CH₂-CH ₂ -CH₂), 15.7 (CH₂-CH ₂ -CH), 17.8 [CH₃-C(O)-CH ₂ ], 18.9 [CH₂-C(O)-NCH₃], 20.0 [C(O)-CH₃], 34.6 (N-CH ₃ ), 42.5 (N-CH-CH₂), 158.5 (C=O), 193.9 [C(O)-CH₃].
Compound 15: ¹H NMR (300 MHz, CDCl₃): δ = 1.63-1.94 (m, 2 H, CH ₂-CH-NCH₃), 2.09-2.60 [m, 4 H, C(O)-CH ₂ -CH ₂ ], 2.94 (s, 3 H, N-CH ₃ ), 4.90 (t, 1 H, CH₂-CH-NCH₃, J = 5.1 Hz), 7.01 (d, 1 H, CH-NH, J = 2.5 Hz), 7.10-7.27 (m, 1 H, aromatic), 7.42 (d, 1 H, aromatic, J = 8.0 Hz), 7.55 (d, 1 H, aromatic, J = 7.6 Hz), 8.83 (br s, N-H). ¹³C NMR (75 MHz, CDCl₃): δ = 17.9 (CH₂-CH ₂ -CH₂), 30.4 (CH-CH ₂ -CH₂), 32.1 [C(O)-CH ₂ ], 34.3 (N-CH ₃ ), 56.9 (-CH-NCH₃), 111.8 (CH, aromatic), 116.2 (C ₀ , aromatic), 118.6 (CH, aromatic), 119.9 (CH, aromatic), 122.4 (CH, aromatic), 122.5 (CH, aromatic), 125.6 (C ₀ , aromatic), 137.0 (HN-C-CH), 171.3 (N-C=O).

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11 For an example, see: Ollero L. Mentink G. Rutjes FPJT. Speckamp WN. Hiemstra H. Org. Lett.  1999,  1:  1331 

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