Synthesis of 3-Sila Derivatives of l-Ascorbic Acid via Mitsunobu Reaction

Abstract

Various 3-sila derivatives of l-ascorbic acid were synthesized in satisfactory yields. The ether link was formed by an unusual aspect of the Mitsunobu reaction, without the need of protecting the remaining hydroxy groups.

Mitsunobu reaction - ethers - silicon compounds - ascorbic acid - bioorganic chemistry

References

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11

All NMR experiments were conducted in CDCl₃. For convenience, proton and carbon chemical shifts for the l-ascorbic acid moiety are detailed for compound 6 only. For all other molecules (7-13) a single list is provided and attributions for l-ascorbic acid (Asc. Ac.) can be derived from the reference compound 6.
General Procedure for Mitsunobu Reaction:
In a typical experiment, a mixture of ascorbic acid (12 mmol) and triphenylphosphine (12 mmol) was suspended in anhyd THF (15 mL) and kept at -10 °C under nitrogen in a Schlenck tube. Then, chloroalkylhydroxysilane (9.6 mmol) and DEAD (12 mmol) in THF (5 mL) were added dropwise over 1 h. The reaction mixture was kept at -10 °C for 24 h before being filtered, concentrated and purified by chromatography.
Compound 6: ¹H NMR: δ = 0.10 [s, 6 H, (CH₃)₂Si], 0.62-0.70 [m, 4 H, (CH₂Si)₂], 1.26-1.38 (m, 2 H, SiCH₂CH ₂), 1.52-1.58 (m, 2 H, CH ₂CH₂O), 1.70 (q, 2 H, J = 7.0 Hz, CH ₂CH₂Cl), 3.51 (t, 2 H, J = 6.3 Hz, CH₂Cl), 3.75-3.80 (m, 2 H, OCH₂), 3.90-3.95 (m, 1 H, H₅), 4.40-4.45 (m, 2 H, H₆), 4.64 (d, 1 H, H₄). ¹³C NMR: δ = -4.70 [(CH₃)₂Si], 9.11 (SiCH₂), 14.2 (SiCH₂), 23.85 (SiCH₂ CH₂), 25.5 (SiCH₂ CH₂), 37.5 (CH₂CH₂Cl), 44.6 (CH₂Cl), 63.48 (CH₂O), 70.04 (C₅), 74.24 (C₆), 76.36 (C₄), 118.20 (C₂), 151.20 (C₃), 172.02 (C₁).
Compound 7: ¹H NMR: δ = 0.10 [s, 6 H, (CH₃)₂Si], 0.62-0.70 [m, 4 H, (CH₂Si)₂], 1.26-1.38 [m, 4 H, (SiCH₂CH ₂)₂], 1.53-1.58 (m, 2 H, CH ₂CH₂O), 1.70 (q, 2 H, J = 7.0 Hz, CH ₂CH₂Cl), 3.5 (t, 2 H, J = 6.3 Hz, CH₂Cl), 3.75-3.80 (m, 2 H, OCH₂), [4.0, 4.45, 4.64 for Asc. Ac.]. ¹³C NMR: δ = -4.70 [(CH₃)₂Si], 9.11 (SiCH₂), 14.2 (SiCH₂), 23.85 (SiCH₂ CH₂), 25.5 (SiCH₂ CH₂), 35.3 [Si(CH₂)₂ CH₂], 37.5 (CH₂CH₂Cl), 44.6 (CH₂Cl), 63.48 (CH₂O), [70.1, 74.2, 76.45, 118.3, 151.12, 172.14 for Asc. Ac.].
Compound 8: ¹H NMR: δ = 0.10 [s, 6 H, (CH₃)₂Si], 0.63-0.70 [m, 4 H, (CH₂Si)₂], 1.28-1.40 {m, 6 H, [SiCH₂(CH₂)₂CH₂]}, 1.51-1.56 (m, 2 H, CH₂CH₂O), 1.72 (q, 2 H, J = 7.1 Hz, CH₂CH₂Cl), 3.5 (t, 2 H, J = 6.3 Hz CH₂Cl), 3.78-3.83 (m, 2 H, OCH₂), [3.92, 4.45, 4.64 for Asc. Ac.]. ¹³C NMR: δ = -4.70 [(CH₃)₂Si], 9.11 (SiCH₂), 14.2 (SiCH₂), 23.85 (SiCH₂CH₂), 25.5 (SiCH₂CH₂), 32.5 [Si(CH₂)₃CH₂], 35.3 {[Si(CH₂)₂CH₂]}, 37.5 (CH₂CH₂Cl), 44.6 (CH₂Cl), 63.48 (CH₂O), [70.12, 74.25, 76.25, 118.5, 151.4, 171.8 for Asc. Ac.].
Compound 9: ¹H NMR: δ = 0.10 [s, 6 H, (CH₃)₂Si], 0.63-0.70 [m, 4 H, (CH₂Si)₂], 1.26-1.38 [m, 8 H, (SiCH₂CH ₂CH ₂)₂], 1.53-1.59 (m, 2 H, CH ₂CH₂O), 1.71 (q, 2 H, J = 7.0 Hz CH ₂CH₂Cl), 3.5 (t, 2 H, J = 6.3 Hz, CH₂Cl), 3.79-3.84 (m, 2 H, OCH₂), [4.01, 4.45, 4.6 for Asc. Ac.]. ¹³C NMR: δ = -4.70 [(CH₃)₂Si], 9.11 (SiCH₂), 14.2 (SiCH₂), 23.85 (SiCH₂ CH₂), 25.5 (SiCH₂ CH₂), 29.1 [Si(CH₂)₄ CH₂], 32.5 [Si(CH₂)₃ CH₂], 35.3 {[Si(CH₂)₂ CH₂]}, 37.5 (CH₂CH₂Cl), 44.6 (CH₂Cl), 63.5 (CH₂O), [70.2, 74.0, 76.4, 118.2, 151.3, 172.1 for Asc. Ac.].
Compound 10: ¹H NMR: δ = 0.22 [s, 6 H, (CH₃)₂Si], 0.53-0.58 [m, 2 H, (CH₂Si], 1.31-1.35 (m, 2 H, SiCH₂CH₂), 1.70 (q, 2 H, J = 7.1 Hz, CH₂CH₂Cl), 2.83 (s, 2 H, CH₂Cl), 3.83-3.89 (m, 2 H, -O-CH₂CH=CH), [3.7, 3.9, 4.67 for Asc. Ac.], 5.85-5.95 (d, 1 H, J = 24.2 Hz, =CH-Si), 6.25-6.31 (td, 1 H, J = 24.2 Hz, =CH-CH₂). ¹³C NMR: δ = -4.82 [(CH₃)₂Si], 9.11 (SiCH₂), 21.0 (SiCH₂CH₂), 29.7 (CH₂Cl), 37.1 (CH₂CH₂Cl), 63.2 (OCH₂C=CH₂), 124.4 (=CH-CH₂), 147.7 (=CH-Si), [69.9, 74.9, 76.5, 119.5, 150.2, 172.0 for Asc. Ac.].
Compound 11: ¹H NMR: δ = 0.22 [s, 6 H, (CH₃)₂Si], 0.52-0.60 [m, 2 H, (CH₂Si], 1.30-1.35 (m, 2 H, SiCH₂CH ₂), 1.70 (q, 2 H, J = 7.1 Hz, CH ₂CH₂Cl), 2.83 (s, 2 H, CH₂Cl), [3.72, 3.93, 4.67 for Asc. Ac.], 5.07-5.11 (m, 2 H, CH ₂C=CH₂), 5.72 (dd, 2 H, ² J = 7.5 Hz, ⁴ J = 2.3 Hz, C=CH₂). ¹³C NMR: δ = -4.82 [(CH₃)₂Si], 9.11 (SiCH₂), 21.0 (SiCH₂ CH₂), 30.5 (CH₂Cl), 37.1 (CH₂CH₂Cl), 63.20 (OCH₂C=CH₂), 128.50 (CH₂ C=CH₂), 143 (CH₂C=CH₂₎, [69.9, 74.9, 76.4, 119.5, 150.2, 172.5 for Asc. Ac.].
Compound 12: ¹H NMR: δ = 0.22 [s, 6 H, (CH₃)₂Si], 2.83 (s, 2 H, CH₂Cl), 3.69-3.75 (m, 2 H, H₆), [3.93, 4.3, 4.7 for Asc. Ac.], 5.85-5.95 (d, 1 H, J = 24.1 Hz;, =CH-Si), 6.25-6.31 (td, 1 H, J = 24.1 Hz, =CH-CH₂). ¹³C NMR. δ = -4.82 [(CH₃)₂Si], 29.70 (CH₂Cl), 63.20 (OCH₂C=CH₂), 124.46 (=CH-CH₂), 147.67 (=CH-Si), [69.90, 74.9, 76.45, 119.45, 150.2, 172.1 for Asc. Ac.].
Compound 13: ¹H NMR: δ = 0.22 [s, 6 H, (CH₃)₂Si], 2.83 (s, 2 H, CH₂Cl), 3.70-3.75 (m, 2 H, H₆), [3.93, 4.3, 4.7 for Asc. Ac.], 5.08-5.14 (m, 2 H, CH ₂C=CH₂), 5.71 (dd, 2 H, ² J = 7.5 Hz, ⁴ J = 2.3 Hz, C=CH ₂). ¹³C NMR: δ = -4.82 [(CH₃)₂Si], 30.5 (CH₂Cl), 63.20 (OCH₂C=CH₂), 128.50 (CH₂ C=CH₂), 143 (CH₂C=CH₂₎, [69.90, 74.90, 76.45, 119.45, 150.20, 172.05 for Asc. Ac.].