Facile Removal Strategy for Allyl and Allyloxycarbonyl Protecting Groups Using Solid-Supported Barbituric Acid under Palladium Catalysis

Abstract

Solid-supported barbituric acid can be used for the palladium(0)-catalyzed deprotection of allyl amines, carbamates, carbonates, esters and ethers. This solid-supported reagent facilitates isolation and purification of the deprotected compounds, especially acids and amines.

allyl and allyloxycarbonyl groups - palladium(0)-catalyzed deprotection - solid-supported barbituric acid - facile isolation - highly polar compounds

References

1 Greene TW. Wuts PGM. Protecting Groups in Organic Synthesis   3rd ed.:  Wiley; New York: 1999. 

Recent reviews on solid-supported reagents, see:

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2b Ley SV. Baxendle IR. Bream RN. Jackson PS. Leach AG. Longbottom DA. Nesi M. Scott JS. Storer RI. Taylor SJ. J. Chem. Soc., Perkin Trans. 1  2000,  3815 

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3 Tsukamoto H. Kondo Y. Synlett  2003,  1061 

4a Garro-Helion F. Merzouk A. Guibé F. J. Org. Chem.  1993,  58:  6109 

4b Kunz H. März J. Angew. Chem., Int. Ed. Engl.  1988,  27:  1375 

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5

A mixture of 4a (5.01 g, 7.21 mmol), dry CH₂Cl₂ (30 mL) and propyl isocyanate (2.7 mL, 28.8 mmol) was agitated at 30 °C for 24 h on an orbit shaker. The resin was filtered and washed with DMF (4 × 40 mL), CHCl₃ (4 × 40 mL), MeOH (4 × 40 mL) and Et₂O (1 × 40 mL) to give 5a. A solution of DCC (8.91 g, 43.2 mmol) in dry THF (12 mL) was added dropwise to a stirred mixture of 5a, malonic acid (2.25 g, 21.6 mmol) and dry THF (36 mL) at 0 °C under Ar. When addition was complete, the mixture was stirred for additional 3 h at r.t. Then, the mixture was diluted with MeOH (100 mL) and heated at 60 °C to dissolve by-products. The resin was collected by filtration and washed with hot DMF (4 × 40 mL), CHCl₃ (4 × 40 mL), MeOH (4 × 40 mL) and Et₂O (1 × 40 mL) to give 1a (6.24 g, quant.).

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8 The synthesis of 1a according to the following report on solution-phase synthesis of barbituric acids was also unsuccessful: Yogo M. Hirota K. Senda S. Chem. Pharm. Bull.  1982,  30:  1333 

9

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12 Carbonate 9 was prepared according to the following report: Lehmann J. Lloyd-Jones GC. Tetrahedron  1995,  51:  8863 

13

Spectra data of 7: ¹H NMR (300 MHz, CDCl₃): δ = 5.70 (br s, 2 H), 4.57 (s, 2 H), 3.84 (t, 2 H, J = 7.7 Hz), 3.75 (s, 2 H), 1.63 (tq, 2 H, J = 7.7, 7.4 Hz), 0.94 (t, 3 H, J = 7.4 Hz). ¹³C NMR (75.4 MHz, CDCl₃): δ = 168.2, 164.8, 164.5, 151.5, 43.7, 43.2, 39.4, 21.1, 11.0. IR(neat): ν_max = 3348, 3199, 2966, 2935, 1659, 1410, 1362, 1289, 1204, 1177, 1140, 1086, 936, 758 cm^-1. MS (EI): m/z (relative intensity) = 227 (5.6) [M]⁺ , 210 (6.5), 184 (96), 169 (37), 143 (77), 98 (81), 56 (100). HRMS (EI) calcd for C₉H₁₃N₃O₄ [M]⁺ 227.0906. Found: 227.0910. Spectra data of 8: ¹H NMR (300 MHz, CDCl₃): δ = 7.27-7.23 (m, 8 H), 6.41 (d, 2 H, J = 15.7 Hz), 6.11 (dt, 2 H, J = 15.7, 7.7 Hz), 5.93-5.61 (m, 2 H), 4.55 (s, 2 H), 3.75 (t, 2 H, J = 7.7 Hz), 3.00-2.87 (m, 4 H), 1.41 (tq, 2 H, J = 7.7, 7.4 Hz), 0.73 (t, 3 H, J = 7.4 Hz). ¹³C NMR (75.4 MHz, CDCl₃): δ = 171.0, 170.5, 168.3, 150.4, 135.1, 134.3, 133.5, 128.8, 127.7, 122.7, 57.2, 43.6, 43.4, 42.5, 21.1, 10.9. IR (neat): ν_max = 3466, 3363, 2966, 2935, 1675, 1490, 1424, 1405, 1283, 1092, 971, 756 cm^-1. MS (EI): m/z (relative intensity) = 527 (32) [M]⁺, 510 (42), 385 (42), 376 (36), 359 (87), 331 (52), 287 (26), 246 (72), 240 (72), 223 (53), 151 (100), 116 (53), 115 (52). HRMS (EI) calcd for C₂₇H₂₇Cl₂N₃O₄ [M]⁺ 527.1379. Found: 527.1401.

14 Högber T. Rämsby S. Ström P. Acta Chem. Scand.  1989,  43:  660