Compound 5a

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Compound data: CIF

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

General procedure for the β-alkylation of enals: To a 15 mL Schlenk tube containing the amine catalyst 1 (0.02 mmol, 20 mol%), the α-heteroatom-substituted silane derivative (0.1 mmol, 1 equiv.), and the enal 2 (0.3 mmol, 3 equiv.), were added the solvent (CH₃CN or CH₃CN/water 3:1, 200 µL) and TFA (0.04 mmol, 3.1 μL). The Schlenk tube was placed under an atmosphere of argon, cooled to – 78 °C, and degassed via vacuum evacuation (5 min), backfilled with argon, and warmed to room temperature. The freeze-pump-thaw cycle was repeated three times, and then the Schlenk tube was sealed with Parafilm and placed into a 3D-printed plastic support mounted on an aluminium block fitted with a 420 nm high-power single LED (λ = 420 nm, irradiance = 41 mW/cm², as controlled by an external power supply; the setup is detailed in Supplementary Figure 4). This setup secured a reliable irradiation while keeping a distance of 1 cm between the reaction vessel and the light source. The reaction was stirred at ambient temperature for the indicated time (generally 24 hours). The solvent was removed in vacuo and the crude mixture was purified by column chromatography on silica gel to give the product 5 in the stated yield and enantiomeric purity. If not otherwise stated, full consumption of the limiting silane substrate (3) was observed at the end of the reaction.

Prepared according to the general procedure outlined above using trimethyl-((phenylthio)-methyl)-silane (0.1 mmol, 19.6 mg), cinnamaldehyde (0.3 mmol, 39.6 mg), aminocatalyst 1b (0.02 mmol, 13.4 mg), trifluoroacetic acid (0.04 mmol, 3.1 µL), acetonitrile (150 µL) and water (50 µL). Time of irradiation: 24 hours. The crude mixture (95% conversion of the silane) was purified by flash column chromatography (hexane/toluene, gradient from 100:0 to 0:100, 3 consecutive purifications) to give the product as a yellow oil (18.6 mg, 73% yield, 90% ee, average of two runs). The enantiomeric excess was determined by HPLC analysis on a Daicel Chiralpak IC-3 column, 95:15 hexane/iPrOH, flow rate 0,8 mL/min, λ = 215 nm: τ_Major = 15.6 min, τ_Minor = 18.7 min, (90% ee); [α]_D²⁶= -32.6 (c = 0.54, CHCl₃, 90% ee). Absolute configuration determined by X-ray analysis on a derivative of compound 5a (see below for details). ¹H NMR (500 MHz, CDCl₃): δ 9.67 (t, J= 1.8Hz, 1H), 7.35-7.27 (m, 6H), 7.26-7.18 (m, 4H), 3.46 (tt J=8.4, 6.1 Hz, 1H), 3,26(dd, J=13.3, 6.3 Hz, 1H), 3.13 (dd, J=13.3, 8.4 Hz, 1H), 3.08 (ddd, J=17.1, 5.9, 1.6 Hz, 1H), 2.82 (ddd, J= 17.1, 8.4, 2 Hz, 1H). ¹³C NMR (126 MHz, CDCl₃): δ 200.9, 142.4, 135.8, 129.7, 129.2, 129.0, 127.6, 127.4, 126.5, 48.8, 40.6, 39.6. HRMS: calculated for C₁₆H₁₆NaOS (M+Na⁺): 279.0814, found: 279.0807.