A Modified U-4CR Reaction with 2-Nitrobenzylamine as an Ammonia Equivalent

Kuangsen Sung; Fu-Lin Chen; Pei-Chun Huang

doi:10.1055/s-2006-951485

LETTER

A Modified U-4CR Reaction with 2-Nitrobenzylamine as an Ammonia Equivalent

Kuangsen Sung*, Fu-Lin Chen, Pei-Chun Huang
Department of Chemistry, National Cheng Kung University, Tainan, Taiwan
Fax: +886(6)2740552; e-Mail: kssung@mail.ncku.edu.tw;

Abstract

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Abstract

A modified U-4CR reaction has been done by using commercially available 2-nitrobenzylamine as an ammonia equivalent and it involves a multi-component reaction, followed by photochemical cleavage of the 2-nitrobenzyl group, which can be done in one pot with good yields.

Key words

multicomponent reaction - photochemistry - peptides - isocyanide - ammonia equivalent

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References

References and Notes

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The general procedure of this method is shown as follows: An aldehyde component (1 mmol), 2-nitrobenzylamine (1 mmol), and MeOH (5 mL) were mixed in a 10-mL quartz flask until the mixture became a clear solution. An isocyanide component (1 mmol) and a carboxylic acid component (1 mmol) were added into the solution and the mixture was stirred at r.t. for 2 d. Then the mixture was irradiated in a quartz flask inside a Rayonet photochemical reactor with four 254-nm lamps at r.t. The reaction was monitored by ¹H NMR spectroscopy, and the reaction was complete in 6-13 h. After the reaction was completed, MeOH was removed by a rotary evaporator, and the residue was purified by column chromatography to get the dipeptides 1a-1e.1a: Light brown solid; mp 119 °C; yield: 93%. ¹H NMR (CD₃OD): δ = 0.94 (d, J = 7.6 Hz, CH₃, 3 H), 0.96 (d, J = 7.6 Hz, CH₃, 3 H), 2.14-2.15 (m, 1 H, CH), 2.20 (s, 3 H, CH₃), 4.37 (d, J = 8.4 Hz, CH, 1 H), 7.06 (d, J = 8.2 Hz, PhH, 2 H), 7.44-7.47 (m, 5 H, PhH), 7.84 (d, J = 8.2 Hz, PhH, 2 H). ¹³C NMR (CDCl₃): δ = 19.46, 19.74, 20.83, 31.19, 60.81, 120.39, 128.23, 129.00, 129.81, 132.12, 133.55, 134.95, 136.82, 167.98, 171.04. IR (thin film): 1654, 1642 (C=O) cm^-1.1b: Brown oil; yield: 84%. ¹H NMR (CDCl₃): δ = 0.89 (d, J = 7.2 Hz, CH₃, 3 H), 1.22 (m, 2 H, CH₂), 1.27-1.29 (m, 4 H, CH₂), 1.55-1.57 (m, 2 H, CH₂), 1.67-1.69 (m, 4 H, CH₂), 2.18 (t, J = 7.4 Hz, CH₂, 2 H), 3.56-3.58 (m, 1 H, CH), 5.37 (s, 1 H, CH), 7.22-7.26 (m, 1 H, PhH), 7.34-7.36 (m, 1 H, PhH), 7.41-7.43 (m, 1 H, PhH), 7.57 (s, 1 H, PhH). ¹³C NMR (CDCl₃): δ = 16.45, 22.75, 28.51, 28.56, 29.07, 35.95, 36.08, 41.00, 60.39, 125.96, 129.70, 133.84, 134.65, 135.41, 144.43, 173.31, 178.13. IR (thin film): 1649, 1634 (C=O) cm^-1.1c: Red brown oil; yield: 89%. ¹H NMR (CDCl₃): δ = 1.22-1.27 (m, 4 H, CH₂), 1.27-1.29 (m, 2 H, CH₂), 1.66-1.70 (m, 4 H, CH₂), 3.67-3.69 (m, 1 H, CH), 5.63 (s, 1 H, CH), 7.36-7.39 (m, 3 H, PhH), 7.49 (d, 2 H, PhH), 7.63-7.66 (m, 2 H, PhH), 7.75-7.79 (m, 1 H, PhH), 8.10-8.14 (m, 2 H, PhH). ¹³C NMR (CDCl₃): δ = 26.06, 26.12, 26.63, 33.50, 33.66, 50.15, 59.25, 125.49, 128.76, 129.32, 129.76, 130.41, 131.88, 133.69, 135.05, 138.63, 147.81, 168.95, 171.14. IR (thin film): 1650, 1629 (C=O) cm^-1.1d: Light yellow oil; yield: 68%. ¹H NMR (CD₃OD): δ = 0.92 (d, J = 6.9 Hz, CH₃, 3 H), 0.95 (d, J = 6.9 Hz, CH₃, 3 H), 1.44 (s, 9 H, CH₃), 1.64-1.66 (m, 2 H, CH₂), 1.73-1.75 (m, 2 H, CH₂), 1.85-1.87 (m, 1 H, CH), 2.10-2.12 (m, 4 H, CH₂), 3.77-3.79 (m, 2 H, CH₂), 4.22 (dd, J = 7.8, 8.1 Hz, 1 H, CH), 5.29 (t, J = 5.4 Hz, 1 H, CH). ¹³C NMR (CDCl₃): δ = 19.24, 25.41, 26.99, 28.25, 29.68, 32.72, 41.96, 44.60, 57.93, 80.59, 97.23, 124.10, 156.32, 169.91, 173.55. IR (thin film): 1701, 1672, 1648 (C=O) cm^-1.1e: Red brown oil; yield: 89%. ¹H NMR (CDCl₃): δ = 0.90 (t, J = 7.3 Hz, CH₃, 3 H), 1.39-1.41 (m, 2 H, CH₂), 1.68-1.70 (m, 1 H, CH₂), 1.88-1.90 (m, 1 H, CH₂), 2.02 (s, 3 H, CH₃), 2.29 (s, 3 H, CH₃), 4.59 (q, J = 6.9 Hz, 1 H, CH), 7.09 (d, J = 8.4 Hz, 2 H, PhH), 7.41 (d, J = 8.4 Hz, 2 H, PhH). ¹³C NMR (CDCl₃): δ = 13.78, 18.89, 20.85, 23.18, 34.30, 53.84, 120.01, 129.41, 134.06, 135.16, 170.01, 170.69. IR (thin film): 1679, 1651 (C=O) cm^-1.