4.1.2. General Procedure for Mitsunobu Reaction

Diisopropyl azodicarboxylate (DIAD) (1.0 mL, 5.1 mmol) was added dropwise to an ice-cooled stirred solution of alcohol 1 (880 mg, 4.8 mmol), phenol 2 (914 mg, 5.1 mmol), and PPh₃ (1.330 g, 5.1 mmol) in freshly distilled tetrahydrofuran (10 mL). After the addition of DIAD, the resulting solution was stirred for 48 h at room temperature. The solvent was distilled off under reduced pressure and the residue was purified by column chromatography using hexane–ethyl acetate–triethylamine (100:10:1) as the eluent.

Methyl 3-(4-(4-(dimethoxymethyl)benzyloxy)phenyl)propanoate (3a). White solid, yield 67%. ¹H NMR (500 MHz, CDCl₃): δ = 7.50–7.40 (m, 4H), 7.11 (d, J = 8.5 Hz, 2H), 6.90 (d, J = 8.5 Hz, 2H), 5.40 (s, 1H), 5.04 (s, 2H), 3.67 (s, 3H), 3.33 (s, 6H), 2.89 (t, J = 7.8 Hz, 2H), 2.60 (t, J = 7.8 Hz, 2H). ¹³C NMR (126 MHz, CDCl₃): δ = 173.4, 157.2, 137.7, 137.3, 132.9, 129.2, 127.2, 126.9, 114.8, 102.8, 69.7, 52.7, 51.6, 35.9, 30.0. HRMS for C₂₀H₂₄O₅⁺ calcd 344.1618, found 344.1613 [M]⁺.

Methyl 3-(4-(3-(dimethoxymethyl)benzyloxy)phenyl)propanoate (3b). Colorless oil, yield 76%. ¹H NMR (300 MHz, CDCl₃): δ = 7.52 (s, 1H), 7.45–7.35 (m, 3H), 7.11 (d, J = 8.5 Hz, 2H), 6.90 (d, J = 8.5 Hz, 2H), 5.41 (s, 1H), 5.05 (s, 2H), 3.67 (s, 3H), 3.34 (s, 6H), 2.94–2.85 (m, 2H), 2.65–2.56 (m, 2H). ¹³C NMR (101MHz, CDCl₃): δ = 173.4, 157.2, 138.4, 137.1, 132.9, 129.2, 128.5, 127.5, 126.3, 125.7, 114.9, 102.9, 69.9, 52.7, 51.5, 35.9, 30.1. HRMS for C₂₀H₂₄O₅⁺ calcd 344.1618, found 344.1613 [M]⁺.

Methyl 3-(3-(4-(dimethoxymethyl)benzyloxy)phenyl)propanoate (3c). Colorless oil, yield 75%. ¹H NMR (300 MHz, CDCl₃): δ = 7.51–7.40 (m, 4H), 7.24–7.16 (m, 1H), 6.85–6.78 (m, 3H), 5.41 (s, 1H), 5.05 (s, 2H), 3.67 (s, 3H), 3.34 (s, 6H), 2.93 (t, J = 7.6 Hz, 2H), 2.64 (t, J = 7.6 Hz, 2H). ¹³C NMR (101MHz, CDCl₃): δ = 173.3, 158.9, 142.1, 137.8, 137.2, 129.5, 127.3 (2C), 126.9 (2C), 120.9, 115.0, 112.4, 102.9, 69.6, 52.6 (2C), 51.6, 35.5, 30.9. HRMS for C₂₀H₂₄O₅⁺ calcd 344.1618, found 344.1619 [M]⁺.

Methyl 3-(3-(3-(dimethoxymethyl)benzyloxy)phenyl)propanoate (3d). Colorless oil, yield 72%. ¹H NMR (400 MHz, CDCl₃): δ = 7.53 (s, 1H), 7.44–7.37 (m, 3H), 7.23–7.18 (m, 1H), 6.85–6.79 (m, 3H), 5.42 (s, 1H), 5.06 (s, 2H), 3.67 (s, 3H), 3.34 (s, 6H), 2.93 (t, J = 7.9 Hz, 2H), 2.63 (t, J = 7.9 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃): δ = 173.3, 158.9, 142.1, 138.4, 137.0, 129.5, 128.5, 127.5, 126.3, 125.8, 120.9, 115.0, 112.5, 102.9, 69.8, 52.7 (2C), 51.6, 35.5, 30.9. HRMS for C₂₀H₂₄O₅⁺ calcd 344.1618, found 344.1621 [M]⁺.