Palladium on Charcoal Catalyzed 3,4-Hydroperoxidation of α-Substituted Enals with Triethylsilane and Water

Abstract

Aldehyde α-hydroperoxides can be accessed from α-substituted acroleins with triethylsilane and water under Pd/C catalysis and aerobic conditions. The reaction is composed of a Pd/C-catalyzed conjugate reduction step and a hydroperoxidation step. The hydroperoxidation takes place via autoxidation of sufficiently stable enols formed in situ by transfer hydrogenation. Upon reduction, 2,2-disubstituted 1,2-diols are obtained directly from aldehydes.

Key words

autoxidation - enols - palladium - oxygen - aldehydes - hydro­peroxides - hydrosilylation

• References and Notes


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• 5 See the Supporting Information for details.
• 6 Preparation of α-Hydroperoxide 4aEt₃SiH (38 mg, 53 μL, 0.33 mmol, 1.1 equiv) was added to a suspension of α-substituted acrolein (1a, 44 mg, 0.30 mmol, 1.0 equiv), water (20 μL) and Pd/C (5 wt%, 1 mg) in EtOAc (1 mL). After 4 min of stirring, gas formation was observed, and the reaction mixture was filtered through a small pad of neutral alumina column. The column was eluted with EtOAc (10 mL). The filtrate was left to oxidize overnight to allow the reaction to proceed to completion. Isolation of the product was unsuccessful. Product 4a decomposes/polymerizes when concentrated. Characterization was carried out from the crude filtrate containing EtOAc and Et₃SiOH (7). IR (film): 3379, 2955, 2877, 1734, 1455, 823, 728, 701, 681 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 9.71 (s, 1 H), 8.40 (br s, 1 H), 7.44–7.08 (m, 5 H), 3.19 (d, 1 H, J = 14.3 Hz), 2.88 (d, 1 H, J = 14.3 Hz), 1.22 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 203.0, 134.5, 130.7, 128.5, 127.2, 89.0, 38.5, 17.1. HRMS (ESI⁺): m/z [M + MeOH + Na] calcd for C₁₁H₁₆O₄Na: 235.0941; found: 235.0945, Δ = –0.4 mDa.
• 7 General Procedure for the Preparation of 2-Methyl-1,2-diolsEt₃SiH (1.65 mmol, 1.1 equiv) was added to the suspension of α-substituted acrolein (1.50 mmol, 1.0 equiv), water (100 μL) and Pd/C (5 wt%, 5 mg) in EtOAc (5 mL). After 10 min of stirring, the reaction mixture was filtered through a small pad of neutral alumina column. The column was eluted with EtOAc (15 mL). The filtrate was stirred overnight to allow the autoxidation to proceed to completion.To the filtrate was added MeOH (20 mL) and NaBH₄ (9.00 mmol, 6.0 equiv). After 3 h of stirring, 40 mL NH₄Cl (aq) was added to quench the reaction. The reaction mixture was extracted with EtOAc (3 × 20 mL). The organic phases were combined, dried with NaSO₄ and concentrated in vacuum. The residue was purified by flash chromatography (silica gel, n-hexane–EtOAc gradient from 80:20 to 50:50) to afford the products. For more details and characterization of the products, see Supporting Information.
• 8 The characterization of enol 6 was carried out from a solution which was partly exposed to the air during the concentration and contains compounds 3a and 4a. If air was completely excluded during the preparation of ¹H NMR sample, only traces of 3a and 4a were observed. The full characterization of 6 was not possible due to significant solvent content of the sample.Characteristic ¹H NMR Resonances of the Enol Intermediate 6.¹H NMR (300 MHz, CDCl₃): δ = 7.36–7.15 (m, 5 H), 6.34 (br dd, 1 H, J = 1.4, 5.9 Hz), 3.42 (s, 1 H), 1.51 (d, 3 H, J = 1.5 Hz). For more details, see Supporting Information.
• 9 Kamachi T, Shimizu K, Yoshihiro D, Igawa K, Tomooka K, Yoshizawa K. J. Phys. Chem. C 2013; 117: 22967
• 10 The exothermic background reaction warms the reaction mixture. The amount of the excess Et₃SiH increases from 0.03 mmol to 0.15 mmol in the scaled reaction.
• 11 No products were lost during the autoxidation, confirmed by internal standard in ¹H NMR analysis.
• 12 Collins KD, Glorius F. Nat. Chem. 2013; 5: 597
• 13 Transfer hydrogenation with Et₃SiD gives the β-deuterated product 3a in 12:88 H/D ratio in the presence of H₂SO₄. See ref 4a.
• 14 For a proposed mechanism, see Supporting Information.