Remarkable Solvent Effect on Pd(0)-Catalyzed Deprotection of Allyl Ethers Using Barbituric Acid Derivatives: Application to Selective and Successive Removal of Allyl, Methallyl, and Prenyl Ethers

Abstract

Pd(0)-catalyzed deprotection of allyl ethers using barbituric acid derivatives in protic polar solvent such as MeOH and aqueous 1,4-dioxane proceeds at room temperature without affecting a wide variety of functional groups. Control of the reaction temperature allows selective and successive cleavage of allyl, methallyl, and prenyl ethers. A study of ligand effects on the deprotection reveals that the improved reactivity in MeOH results from the accelerated oxidative addition to Pd(0).

Key words

barbituric acid - Pd(0)-catalyzed deprotection - allyl ethers - protic polar solvent - methallyl ethers - prenyl ethers

References and Notes

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6

Representative Procedure for Deprotection of Allyl Ether: To a test tube containing 2a (0.13 mmol), 1a (0.27 mmol), and Pd(PPh₃)₄ (7 µmol) was added MeOH (0.4 mL) under argon. The resulting mixture was sealed with a screw cap and agitated at r.t. for 1 h. The mixture was partitioned between EtOAc and sat. aq Na₂CO₃ and the aqueous layer was extracted with EtOAc (2 ×). The combined organic layers were washed with brine, dried over MgSO₄, and concentrated in vacuo. The residue was purified by silica gel chromatography to yield the deallylated product 3a.

10

Characterization data for compounds 9-14.
4-Methoxyphenyl 3-O-Allyl-4-O-benzyl-2-O-methallyl-6-O-prenyl-β-d-galactopyranoside (9): ¹H NMR (400 MHz, CDCl₃): δ = 7.25-7.40 (m, 5 H), 6.99 (d, J = 8.8 Hz, 2 H), 6.78 (d, J = 8.8 Hz, 2 H), 5.93 (ddt, J = 5.6, 10.4, 17.2 Hz, 1 H), 5.33 (d, J = 17.2 Hz, 1 H), 5.27 (t, J = 6.8 Hz, 1 H), 5.18 (d, J = 10.4 Hz, 1 H), 5.01 (s, 1 H), 4.96 (d, J = 11.6 Hz, 1 H), 4.87 (s, 1 H), 4.77 (d, J = 7.6 Hz, 1 H), 4.67 (d, J = 11.6 Hz, 1 H), 4.33 (d, J = 12.0 Hz, 1 H), 4.23 (d, J = 12.0 Hz, 1 H), 4.19 (d, J = 5.6 Hz, 2 H), 3.82-3.95 (m, 4 H), 3.75 (s, 3 H), 3.51-3.61 (m, 3 H), 3.44 (dd, J = 2.8, 9.6 Hz, 1 H), 1.78 (s, 3 H), 1.72 (s, 3 H), 1.62 (s, 3 H). ¹³C NMR (100 MHz, C₆D₆): δ = 155.8, 152.4, 143.3, 139.6, 136.2, 135.7, 128.5, 128.1, 127.6, 122.0, 119.2, 116.0, 114.9, 111.7, 103.9, 82.5, 79.3, 77.1, 75.2, 74.5, 74.0, 71.9, 68.5, 68.0, 55.2, 25.8, 19.9, 18.0. IR (neat): 2914, 2875, 1507, 1233, 1102, 1054, 1027, 822, 746 cm^-1. MS (FAB): m/z = 538 [M]⁺. HRMS (FAB): m/z [M]⁺ calcd for C₃₂H₄₂O₇: 538.2928; found: 538.2916.
4-Methoxyphenyl 4-O-Benzyl-2-O-methallyl-6-O-prenyl-β-d-galactopyranoside (10): ¹H NMR (600 MHz, CDCl₃): δ = 7.39 (d, J = 7.2 Hz, 2 H), 7.35 (dd, J = 7.2, 7.2 Hz, 2 H), 7.30 (t, J = 7.2 Hz, 1 H), 6.99 (d, J = 9.0 Hz, 2 H), 6.80 (d, J = 9.0 Hz, 2 H), 5.29 (t, J = 6.3 Hz, 1 H), 5.01 (s, 1 H), 4.89 (s, 1 H), 4.85 (d, J = 11.7 Hz, 1 H), 4.77 (d, J = 7.2 Hz, 1 H), 4.75 (d, J = 11.7 Hz, 1 H), 4.40 (d, J = 12.0 Hz, 1 H), 4.18 (d, J = 12.0 Hz, 1 H), 3.96 (dd, J = 7.2, 11.4 Hz, 1 H), 3.88-3.92 (m, 2 H), 3.76 (s, 3 H), 3.68-3.71 (m, 3 H), 3.56-3.63 (m, 2 H), 2.39-2.43 (br s, 1 H), 1.77 (s, 3 H), 1.72 (s, 3 H), 1.63 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 155.2, 151.5, 142.4, 138.5, 137.5, 128.4, 128.1, 127.8, 120.7, 118.3, 114.5, 112.5, 102.8, 79.6, 76.7, 75.5, 75.1, 74.1, 73.9, 68.2, 67.8, 55.6, 25.8, 19.7, 18.0. IR (neat): 3300-3600 (br), 2914, 2865, 1507, 1453, 1378, 1214, 1061, 826, 747 cm^-1. MS (EI): m/z (%) = 498 [M]⁺ (0.45), 430 (0.36), 374 (1.9), 307 (5.6), 262 (2.6), 214 (5.3), 192 (15), 145 (15), 124 (100), 91 (94). HRMS (EI): m/z [M]⁺ calcd for C₂₉H₃₈O₇: 498.2615; found: 498.2616.
4-Methoxyphenyl 3-O-Benzoyl-4-O-benzyl-2-O-methallyl-6-O-prenyl-β-d-galactopyranoside (11): ¹H NMR (400 MHz, CDCl₃): δ = 8.04 (dd, J = 1.2, 8.0 Hz, 2 H), 7.56 (tt, J = 1.2, 8.0 Hz, 1 H), 7.43 (dd, J = 8.0, 8.0 Hz, 2 H), 7.20-7.30 (m, 5 H), 7.03 (d, J = 9.2 Hz, 2 H), 6.81 (d, J = 9.2 Hz, 2 H), 5.24 (t, J = 6.8 Hz, 1 H), 5.24 (dd, J = 3.4, 10.2 Hz, 1 H), 4.92 (d, J = 7.6 Hz, 1 H), 4.89 (s, 1 H), 4.76 (s, 1 H), 4.72 (d, J = 11.8 Hz, 1 H), 4.58 (d, J = 11.8 Hz, 1 H), 4.31 (d, J = 11.6 Hz, 1 H), 4.13 (dd, J = <1.0, 3.4 Hz, 1 H), 4.12 (d, J = 11.6 Hz, 1 H), 4.08 (dd, J = 7.6, 10.2 Hz, 1 H), 3.95 (dd, J = 6.8, 11.4 Hz, 1 H), 3.88 (dd, J = 6.8, 11.4 Hz, 1 H), 3.82 (ddd, J = <1.0, 6.8, 6.8 Hz, 1 H), 3.76 (s, 3 H), 3.56-3.64 (m, 2 H), 1.72 (s, 3 H), 1.62 (s, 3 H), 1.58 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 165.6, 155.1, 151.4, 142.1, 137.9, 137.2, 133.1, 129.7, 129.7, 128.3, 128.1, 127.9, 127.5, 120.7, 118.4, 114.4, 112.6, 103.0, 77.0, 76.8, 75.7, 75.0, 74.3, 73.5, 67.9, 67.8, 55.6, 25.8, 19.6, 18.1. IR (neat): 2931, 2867, 1719, 1507, 1451, 1270, 1216, 1067, 903, 826, 749, 710 cm^-1. MS (EI): m/z (%) = 602 [M]⁺ (1.3), 479 (8.7), 411 (21), 393 (5.7), 339 (6.2), 303 (4.6), 249 (20), 214 (15), 192 (18), 149 (22), 91 (100). HRMS (EI): m/z [M]⁺ calcd for C₃₆H₄₂O₈: 602.2877; found: 602.2867.
4-Methoxyphenyl 3-O-Benzoyl-4-O-benzyl-6-O-prenyl-β-d-galactopyranoside (12): ¹H NMR (400 MHz, CDCl₃): δ = 8.05 (dd, J = 1.2, 8.0 Hz, 2 H), 7.56 (tt, J = 1.2, 8.0 Hz, 1 H), 7.42 (dd, J = 8.0, 8.0 Hz, 1 H), 7.20-7.30 (m, 5 H), 7.03 (d, J = 9.2 Hz, 2 H), 6.80 (d, J = 9.2 Hz, 2 H), 5.28 (t, J = 6.8 Hz, 1 H), 5.22 (dd, J = 3.2, 10.4 Hz, 1 H), 4.86 (d, J = 8.0 Hz, 1 H), 4.73 (d, J = 11.6 Hz, 1 H), 4.59 (d, J = 11.6 Hz, 1 H), 4.35 (dd, J = 8.0, 10.4 Hz, 1 H), 4.15 (dd, J = <1.0, 3.2 Hz, 1 H), 3.96 (dd, J = 7.2, 11.6 Hz, 1 H), 3.88 (dd, J = 7.2, 11.6 Hz, 1 H), 3.85 (ddd, J = <1.0, 7.2, 7.2 Hz, 1 H), 3.76 (s, 3 H), 3.56-3.65 (m, 2 H), 2.49-2.55 (br s, 1 H), 1.72 (s, 3 H), 1.62 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 166.0, 155.3, 151.1, 137.9, 137.3, 133.2, 129.8, 129.5, 128.4, 128.1, 127.8, 127.6, 120.6, 118.5, 114.4, 102.6, 75.8, 75.1, 74.2, 73.8, 69.7, 67.8, 67.8, 55.6, 25.8, 18.1. IR (neat): 3250-3600(br), 2912, 2836, 1717, 1507, 1451, 1273, 1216, 1065, 1027, 827, 748, 712 cm^-1. MS (EI): m/z (%) = 548 [M]⁺ (0.34), 425 (8.5), 357 (34), 249 (4.0), 214 (11), 192 (13), 124 (100), 91 (97). HRMS (EI): m/z [M]⁺ calcd for C₃₂H₃₆O₈: 548.2410; found: 548.2411.
4-Methoxyphenyl 2-O-Acetyl-3-O-benzoyl-4-O-benzyl-6-O-prenyl-β-d-galactopyranoside (13): ¹H NMR (400 MHz, CDCl₃): δ = 8.01 (d, J = 7.8 Hz, 2 H), 7.57 (t, J = 7.8 Hz, 1 H), 7.43 (dd, J = 7.8, 7.8 Hz, 2 H), 7.16-7.28 (m, 5 H), 6.98 (d, J = 9.0 Hz, 2 H), 6.80 (d, J = 9.0 Hz, 2 H), 5.79 (dd, J = 7.6, 10.4 Hz, 1 H), 5.29 (t, J = 6.8 Hz, 1 H), 5.21 (dd, J = 3.2, 10.4 Hz, 1 H), 4.98 (d, J = 7.6 Hz, 1 H), 4.71 (d, J = 11.6 Hz, 1 H), 4.56 (d, J = 11.6 Hz, 1 H), 4.20 (dd, J = <1.0, 3.2 Hz, 1 H), 3.96 (dd, J = 7.2, 11.6 Hz, 1 H), 3.89 (dd, J = 7.2, 11.6 Hz, 1 H), 3.87 (ddd, J = 1.0, 7.2, 7.2 Hz, 1 H), 3.76 (s, 3 H), 3.58-3.66 (m, 2 H), 1.98 (s, 3 H), 1.72 (s, 3 H), 1.63 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 169.3, 165.7, 155.3, 151.2, 137.7, 137.3, 133.4, 129.8, 129.0, 128.5, 128.1, 127.9, 127.5, 120.6, 118.5, 114.4, 100.8, 75.0, 74.5, 73.8, 73.8, 69.5, 67.8, 67.7, 55.6, 25.8, 20.8, 18.0. IR (neat): 2935, 2869, 1752, 1719, 1507, 1272, 1212, 1067, 1027, 828, 749, 714 cm^-1. MS (EI): m/z (%) = 590 [M]⁺ (0.26), 467 (3.7), 399 (54), 339 (5.0), 277 (30), 249 (27), 175 (8.5), 124 (30), 91 (100). HRMS (EI): m/z [M]⁺ calcd for C₃₄H₃₈O₉: 590.2516; found: 590.2518.
4-Methoxyphenyl 2-O-Acetyl-3-O-benzoyl-4-O-benzyl-β-d-galactopyranoside (14): ¹H NMR (400 MHz, CDCl₃): δ = 8.05 (dd, J = 1.2, 8.0 Hz, 2 H), 7.60 (tt, J = 1.2, 8.0 Hz, 1 H), 7.47 (dd, J = 8.0, 8.0 Hz, 2 H), 7.23-7.26 (m, 5 H), 6.96 (d, J = 9.2 Hz, 2 H), 6.81 (d, J = 9.2 Hz, 2 H), 5.81 (dd, J = 8.0, 10.4 Hz, 1 H), 5.22 (dd, J = 2.8, 10.4 Hz, 1 H), 5.01 (d, J = 8.0 Hz, 1 H), 4.76 (d, J = 11.6 Hz, 1 H), 4.48 (d, J = 11.6 Hz, 1 H), 4.13 (dd, J = <1.0, 2.8 Hz, 1 H), 3.84-3.90 (m, 1 H), 3.73-3.78 (m, 4 H), 3.55-3.62 (m, 1 H), 2.00 (s, 3 H), 1.58-1.65 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 169.4, 165.8, 155.3, 151.0, 137.1, 133.6, 129.8, 128.9, 128.6, 128.4, 128.3, 128.0, 118.3, 114.5, 100.5, 75.2, 72.7, 74.6, 73.1, 69.4, 61.6, 55.6, 20.8. IR (neat): 3350-3600 (br), 2935, 2883, 1752, 1719, 1507, 1272, 1212, 1069, 1027, 828, 749, 698 cm^-1. MS (EI): m/z (%) = 522 [M]⁺ (0.35), 399 (22), 339 (3.0), 277 (9.5), 249 (18), 217 (3.5), 175 (8.5), 124 (25), 91 (100). HRMS (EI): m/z [M]⁺ calcd for C₂₉H₃₀O₉: 522.189; found: 522.1868.

17

There are a few reports on carboxylic acids promoted Tsuji-Trost reaction.^14a,15g,h In our systems, barbituric acids play dual roles as acids and nucleophiles.

18

Less acidic acyclic 1,3-dicarbonyl compounds did not scavenge the allyl group of 2a in aqueous 1,4-dioxane at room temperature. This result is quite different from the aqueous biphasic Tsuji-Trost reaction developed by Shinokubo and Oshima.^14b Our system does not require biphasic systems, water-soluble TPPTS [trisodium salt of tri(m-sulfophenyl)phosphine] as a ligand, and additional base.