A Mild and Efficient Catalytic Strecker Reaction of N-Alkoxycarbonylamino Sulfones with Trimethylsilyl Cyanide Using Indium(III) Chloride: A Facile Synthesis of α-Aminonitriles [¹]

Abstract

The Strecker reaction of N-alkoxycarbonylamino ­sulfones with trimethylsilyl cyanide in the presence of catalytic amount of indium(III) chloride at room temperature produces the corresponding protected α-aminonitriles in high yields.

Key words

Strecker reaction - N-alkoxycarbonylamino sulfones - trimethylsilyl cyanide - protected α-aminonitrile - indium(III) ­chloride

1

Part 179 in the series ‘Studies on novel synthetic methodologies’.

References and Notes

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1

Part 179 in the series ‘Studies on novel synthetic methodologies’.

19

General Procedure for the Synthesis of α-Aminonitriles
Trimethylsilyl cyanide (2, 120 mg, 1.2 mmol) was added dropwise to a solution of an N-alkoxycabonylamino sulfone 1 (1 mmol) and InCl₃ (22.1 mg, 10 mol%) in CH₂Cl₂ (5 mL) under nitrogen. The mixture was stirred, and the reaction was monitored by TLC. After completion, the reaction was quenched with distilled H₂O (5 mL) and the mixture was extracted with EtOAc (3 ×10 mL). The combined organic portions were washed with H₂O (2 × 10 mL) and sat. aq NH₄Cl solution (2 × 10 mL), dried over anhyd Na₂SO₄, and concentrated under vacuum. The crude product was subjected to column chromatography (silica gel, hexane-EtOAc = 85:15 to 90:10) to obtain pure protected α-aminonitrile.
Spectroscopic Data of some Representative Products
2-(Benzyloxycarbonylamino)-2-(phenyl)acetonitrile (3a)
White solid; mp 107-109 ˚C. IR (KBr): 3278, 3031, 1694, 1521, 1451 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 7.55-7.24 (10 H, m), 5.80 (1 H, br d, J = 8.7 Hz), 5.37 (1 H, br d, J = 8.7 Hz), 5.12 (2H, s). ^¹³C NMR (50 MHz, CDCl₃): δ = 155.2, 135.7, 133.3, 129.9, 129.6, 128.9, 128.7, 128.5, 127.1, 117.6, 68.2, 46.8. MS-FAB: m/z = 267 [M + H]⁺. ESI-HRMS: m/z calcd for C₁₆H₁₄N₂O₂Na [M + Na]⁺: 289.0952; found: 289.0951.
2-(Benzyloxycarbonylamino)-2-(4-methoxyphenyl)-acetonitrile (3g)
White solid; mp 113-115 ˚C. IR (KBr): 3296, 1688, 1612, 1519, 1253 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 7.43 (2 H, d, J = 8.0 Hz), 7.40-7.31 (5 H, m), 6.92 (2 H, d, J = 8.0 Hz), 5.76 (1 H, d, J = 8.0 Hz), 5.22 (1 H, d, J = 8.0 Hz), 5.18 (2 H, s), 3.82 (3 H, s). ^¹³C NMR (50 MHz, CDCl₃): δ = 160.7, 155.2, 135.7, 128.8, 128.7, 128.6, 128.5, 125.2, 117.8, 114.9, 68.1, 55.6, 46.3. ESI-MS: m/z = 297 [M + H]⁺, 319 [M+Na]⁺. ESI-HRMS: m/z calcd for C₁₇H₁₆N₂O₃Na [M + Na]⁺: 319.1058; found: 319.1069.
2-(Benzyloxycarbonylamino)-2-(3-nitrophenyl)aceto-nitrile (3j) White solid; mp 112-114 ˚C. IR (KBr): 3280, 3057, 1692, 1532 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 8.37 (1 H, t, J = 7.0 Hz), 8.33 (1 H, dd, J = 8.0, 2.0 Hz), 7.83 (1 H, dd, J = 8.0, 2.0 Hz), 7.62 (1 H, t, J = 8.0 Hz), 7.35 (5 H, br s), 5.95 (1 H, br d, J = 8.0 Hz), 5.52 (1 H, d, J = 8.0 Hz), 5.17 (2 H, s). ^¹³C NMR (50 MHz, CDCl₃): δ = 155.2, 148.9, 135.6, 135.3, 133.0, 130.7, 128.7, 128.5, 124.7, 122.2, 116.6, 68.5, 46.0. MS-FAB: m/z = 311 [M]⁺. ESI-HRMS: m/z calcd for C₁₆H₁₃N₃O₄Na [M + Na]⁺: 334.0803; found: 334.0820.
2-(Benzyloxycarbonylamino)-2-(2-naphthyl)aceto-nitrile (3l)
White solid; mp 133-135 ˚C. IR(neat): 3283, 1690, 1517, 1289 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 7.98 (1 H, d, J = 2.0 Hz), 7.90-7.79 (3 H, m), 7.58-7.45 (3 H, m), 7.38-7.27 (5 H, m), 5.99 (1 H, d, J = 8.0 Hz), 5.39 (1 H, d, J = 8.0 Hz), 5.18 (2 H, s). ^¹³C NMR (50 MHz, CDCl₃): δ = 155.1, 135.5, 133.5, 133.0, 130.2, 129.6, 128.7, 128.6, 128.3, 128.2, 127.8, 127.3, 127.1, 126.5, 123.9, 117.5, 68.0, 46.8. ESI-MS: m/z = 317 [M + H]⁺. ESI-HRMS: m/z calcd for C₂₀H₁₆N₂O₂Na [M + Na]⁺: 339.1109; found: 339.1125.
2-(Benzyloxycarbonylamino)-2-(2-furyl)acetonitrile (3m)
Pale grey solid; mp 104-106 ˚C. IR(neat): 3270, 1694, 1532, 1255 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 7.42 (1 H, d, J = 1.5 Hz), 7.39-7.22 (5 H, m), 6.52 (1 H, d, J = 3.0 Hz), 6.38 (1 H, dd, J = 3.0, 1.5 Hz), 5.89 (1 H, d, J = 8.0 Hz), 5.45 (1 H, d, J = 8.0 Hz), 5.14 (2 H, s). ^¹³C NMR (50 MHz, CDCl₃): δ = 154.8, 145.0, 144.1, 135.3, 128.6, 128.5, 128.2, 115.6, 110.9, 109.8, 68.0, 40.5. ESI-MS: m/z = 257 [M + H]⁺. ESI-HRMS: m/z calcd for C₁₄H₁₂N₂O₃Na [M + Na]⁺: 279.0745; found: 279.0742.
2-(Benzyloxycarbonylamino)-3-methylbutyronitrile (3r)
Colorless oil. IR(neat): 3324, 3035, 1706, 1527, 1266, 1237 cm^-¹. ^¹H NMR (200 MHz, CDCl₃): δ = 7.35-7.26 (5 H, br s), 5.16 (1 H, br d, J = 8.0 Hz), 5.12 (2 H, s), 4.50 (1 H, t, J = 8.0 Hz), 2.03 (1 H, m), 1.11 (3 H, d, J = 7.0 Hz), 1.07 (3 H, d, J = 7.0 Hz). ^¹³C NMR (50 MHz, CDCl₃): δ = 155.5, 135.8, 128.8, 128.7, 127.0, 117.9, 67.8, 49.0, 31.8, 18.9, 18.2. MS-FAB: m/z 233 [M + H]⁺. ESI-HRMS: m/z calcd for C₁₃H₁₆N₂O₂Na [M + Na]⁺: 255.1109; found: 255.1102.