Selective Deprotection Of tert-Butyldimethylsilyl Ether With Lithium Bromide And 18-Crown-6

Abstract

Lithium bromide, in the presence of a crown ether, has been found to selectively remove primary tert-butyldimethylsilyl ethers under controlled conditions. This selectivity has been utilized to synthesize 3′-TBDMS-2′-deoxyuridine in one step from the diprotected compound.

Notes

The synthesis of 1 will be reported separately.

The compounds 11 (50%), 10 (30%) and the 2′-deoxyuridine (20%) were obtained.

The analytical data for the compounds 1–12 are as follows: TBDMS Ether 1(mixture of diastereomers). 300MHz ¹H NMR (CDCl₃) δ 7.9 (m, 2H), 7.55 (m. 3H), 5.1 (m. 1H), 4.14–3.10 (m, 5H), 3.08, 2.65 (s, 3H), 2.4–2.0 (m, 2H), 0.9 (s, 9H), 0.1 (s, 6H); 75 MHz ¹³C NMR (CDCl₃) δ 137.2, 136.3, 133.1, 132.9, 129.3, 129.0, 127.8, 127.3, 81.9, 79.6, 67.4, 64.3, 63.2, 61.5, 46.9, 46.6, 38.3, 38.1, 31.8, 31.0, 26.0, 25.8, 18.2, 18.1, -5.4, -5.5; FABMS [(M+H)⁺]=450 m/e. HRMS calc. for C₁₈H₃₂NO₆SiS₂: 450.1440; found: 450.1440. Alcohol 2 (mixture of diastereomers). 400MHz ¹H NMR (CDCl₃) δ 7.9 (m, 2H), 7.6 (m. 3H), 5.1 (m, 1H), 4.15–3.20 (m, 5H), 3.1, 2.7 (s, 3H), 2.53 (m, 1H), 2.4–2.0 (m, 2H); 100 MHz ¹³C NMR (CDCl₃) δ 136.3, 135.7, 133.4, 133.2, 129.5, 129.2, 127.9, 127.5, 81.8, 79.5, 67.6, 63.8, 63.6, 61.5, 47.2, 47.0, 38.4, 38.1, 31.6, 31.1; FABMS [(M+H)⁺]=336 m/e. HRMS calc. for C₁₂H₁₈NO₆S₂: 336.0576; found: 336.0578. 1,10-bis-TBDMS-decanediol (3). 200MHz ¹H NMR (CDCl₃) δ 3.6 (t, J, = 8 Hz, 4H), 1.65–1.15 (m, 16H), 0.9 (s, 18H), 0.05 (s, 12H). 1,10-Decanediol (4). 200MHz ¹H NMR (CDCl₃) δ 3.65 (t, J, = 8 Hz, 4H), 1.8–1.1 (m, 18H). Cycloheptanol-TBDMS Ether (5). 200MHz ¹H NMR (CDCl₃) δ 3.85 (m, 1H), 1.95–1.2 (m, 12H), 0.9 (s, 9H), 0.05 (s, 6H). Cycloheptanol (6). 200MHz ¹H NMR (CDCl₃) δ 3.85 (m, 1H), 2.1–1.1 (m, 13H). 1,5-bis-TBDMS-hexanediol (7). 200MHz ¹H NMR (CDCl₃) δ 3.75 (m, 1H), 3.6 (t, J, = 6.3 Hz, 2H), 1.6–1.2 (m, 6H), 1.06 (d, J, = 6.1 Hz, 3H), 0.89, 0.88 (2xs, 18H), 0.05 (s, 12H). 5-TBDMS-hexane-1,5-diol (8). 200MHz ¹H NMR (CDCl₃) δ 3.79 (m, 1H), 3.65 (t, J, = 6.4 Hz, 2H), 1.7–1.3 (m, 7H), 1.12 (d, J, = 6.1 Hz, 3H), 0.88 (s, 9H), 0.05 (s, 6H); FABMS [(M+H)⁺]=233 m/e. 1-TBDMS-hexane-1,5-diol (9). 200MHz ¹H NMR (CDCl₃) δ 3.83 (m, 1H), 3.6 (t, J, = 6.4 Hz, 2H), 1.7–1.3 (m, 7H), 1.2 (d, J, = 8.0 Hz, 3H), 0.9 (s, 9H), 0.05 (s, 6H). 3′,5′-bis-TBDMS-2′-deoxyuridine (10). 200MHz ¹H NMR (CDCl₃) δ 8.15 (bs, 1H), 7.9 (d, J, = 8.4 Hz,1H), 6.28 (t, J, = 6.4 Hz. 1H), 5.67 (d, J, = 8.4 Hz, 1H), 4.42 (m, 1H), 4.0–3.7 (m, 3H), 2.45–1.95 (m, 2H), 0.95, 0.90 (2xs, 18H), 0.15, 0.10 (2xs, 12H); FABMS [(M+H)⁺]=457 m/e. HRMS calc. for C₂₁H₄₁N₂O₅Si₂: 457.2554; found: 457.2553. 3′-TBDMS-2′-deoxyuridine (11). 400MHz ¹H NMR (CDCl₃) δ 8.73 (bs, 1H), 7.64 (d, J, = 8.24 Hz,1H), 6.17 (t, J, = 6.4 Hz, 1H), 5.73 (d, J, = 8.24 Hz, 1H), 4.45 (m, 1H), 4.0–3.6 (m, 3H), 2.57–2.4 (m, 1H), 2.38–2.15 (m, 2H), 0.89 (s, 9H), 0.08 (s, 6H); FABMS [(M+H)⁺]=343 m/e. HRMS calc. for C₁₅H₂₇N₂O₅Si: 343.1689; found: 343.1695. 3′,5′-bis-TBDMS-2′-deoxythymidine (11). 200MHz ¹H NMR (CDCl₃) δ 7.9 (bs, 1H), 7.45 (s, 1H), 6.32 (t, J, = 7.0 Hz., 1H), 4.4 (m, 1H), 4.0–3.65 (m, 3H), 2.35–1.95 (m, 2H), 1.9 (s, 3H), 0.95, 0.90 (2xs, 18H), 0.13, 0.10 (2xs, 12H); FABMS [(M+H)⁺]=471 m/e. 3′-TBDMS-2′-deoxythymidine (12). 400MHz ¹H NMR (CDCl₃) δ 8.95 (bs, 1H), 7.38 (s, 1H), 6.15 (t, J, = 7.0 Hz, 1H), 4.50 (m, 1H), 4.0–3.7 (m, 3H), 2.77 (bs, 1H), 2.4–2.2 (m, 2H), 1.9 (s, 3H), 0.90 (s, 9H), 0.10 (s, 6H); FABMS [(M+H)⁺]=357 m/e. HRMS calc. for C₁₆H₂₉N₂O₅Si: 357.1846; found: 357.1846.