4.3. General Procedure for Gold(I) Catalyzed Cascade Reactions: Preparation of 4a–n
Substrate 1 (1 eq.) and dihydrofuran (10 eq.) were placed in a 0.5–2 mL microwave reactor and dissolved in anhydrous 1,4-dioxane. Catalyst A (0.05 eq.) was added into the reactor. Once all the reagents were dissolved, the reactor was placed into the microwave for 20 min at 60 °C. The reaction mixture was filtered through a pad of Celite with CH2Cl2 as eluent. After solvent evaporation under reduced pressure, purification of the crude by flash column chromatography provided the furopyran adduct 4.
4.3.1. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-phenylpropa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4a
Compound 4a was prepared following the general procedure using compound 1a (20 mg, 0.072 mmol, 1 eq.), dihydrofuran (51 mg, 0.72 mmol, 10 eq.) and catalyst A (3 mg, 0.004 mmol, 0.05 eq.) in 1,4-dioxane (0.4 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4a (64%, 16 mg, 0.046 mmol) as an amorphous white solid. 1H NMR (400 MHz, CDCl3) δ 7.28–7.24 (m, 1H), 7.23–7.11 (m, 5H), 7.11–7.05 (m, 1H), 6.89 (td, J = 7.5, 1.2 Hz, 1H), 6.62 (dd, J = 8.1, 1.2 Hz, 1H), 5.31 (d, J = 5.6 Hz, 1H), 4.81 (dd, J = 11.7, 1.3 Hz, 1H), 4.42 (d, J = 11.7 Hz, 1H), 4.33 (td, J = 8.4, 3.8 Hz, 1H), 4.10 (td, J = 8.4, 7.3 Hz, 1H), 3.87–3.73 (m, 2H), 3.48–3.37 (m, 1H), 2.75 (td, J = 9.4, 5.6 Hz, 1H), 2.48 (dtd, J = 12.8, 7.3, 3.8 Hz, 1H), 2.30 (dq, J = 12.7, 8.5 Hz, 1H), 2.13–1.99 (m, 1H), 1.70 (dtd, J = 12.9, 9.6, 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.3, 153.0, 137.0, 129.0, 128.4, 127.5, 126.8, 126.5, 125.2, 120.8, 116.0, 105.1, 101.6, 85.0, 78.3, 67.8, 67.0, 49.7, 49.6, 33.3, 27.0. HRMS ESI: Calculated for C23H23O3 [M + H]+ 347.1647, found 347.1642 (Diff.: 0.31 ppm).
4.3.2. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(p-tolyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4b
Compound 4b was prepared following the general procedure using compound 1b (50 mg, 0.172 mmol, 1 eq.), dihydrofuran (120 mg, 1.72 mmol, 10 eq.) and catalyst A (7 mg, 0.009 mmol, 0.05 eq.) in 1,4-dioxane (0.4 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4b (80%, 50 mg, 0.138 mmol) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 7.24 (dd, J = 7.7, 1.6 Hz, 1H), 7.10 (td, J = 7.7, 1.7 Hz, 1H), 7.05 (d, J = 8.4 Hz, 2H), 7.01 (d, J = 8.4 Hz, 2H), 6.90 (dd, J = 7.5, 1.2 Hz, 1H), 6.64 (dd, J = 8.1, 1.2 Hz, 1H), 5.25 (d, J = 5.7 Hz, 1H), 4.76 (d, J = 11.5 Hz, 1H), 4.32 (td, J = 8.8, 3.6 Hz, 2H), 4.09 (td, J = 8.7, 7.2 Hz, 1H), 3.88–3.70 (m, 2H), 3.38 (dd, J = 8.9, 7.1 Hz, 1H), 2.72 (td, J = 9.5, 5.6 Hz, 1H), 2.44 (dtd, J = 12.7, 7.1, 3.5 Hz, 1H), 2.38–2.22 (m, 4H), 2.15–1.99 (m, 1H), 1.70 (dq, J = 12.8, 8.9 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.1, 153.0, 136.5, 134.1, 129.1, 129.0, 127.6, 126.3, 125.2, 120.7, 116.0, 104.6, 101.5, 85.0, 78.1, 67.7, 67.0, 49.9, 49.8, 33.3, 27.0, 21.1. HRMS ESI: Calculated for C24H25O3 [M + H]+ 361.1804, found 361.1793 (Diff.: 1.59 ppm).
4.3.3. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(3-methoxyphenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4c
Compound 4c was prepared following the general procedure using compound 1c (51 mg, 0.167 mmol, 1 eq.), dihydrofuran (117 mg, 1.67 mmol, 10 eq.) and catalyst A (6 mg, 0.008 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4c (61%, 39 mg, 0.102 mmol) as an amorphous yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.29–7.20 (m, 1H), 7.16–7.05 (m, 2H), 6.88 (td, J = 7.5, 1.2 Hz, 1H), 6.78 (dt, J = 7.9, 1.2 Hz, 1H), 6.70–6.59 (m, 3H), 5.35 (d, J = 5.7 Hz, 1H), 4.81 (dd, J = 11.7, 1.4 Hz, 1H), 4.52–4.37 (m, 1H), 4.31 (td, J = 8.4, 3.9 Hz, 1H), 4.08 (td, J = 8.4, 7.4 Hz, 1H), 3.94–3.65 (m, 5H), 3.47–3.26 (m, 1H), 2.75 (td, J = 9.5, 5.7 Hz, 1H), 2.46 (dtd, J = 12.7, 7.3, 3.9 Hz, 1H), 2.28 (dq, J = 12.6, 8.4 Hz, 1H), 2.05 (dddd, J = 12.9, 9.2, 7.2, 4.8 Hz, 1H), 1.69 (ddt, J = 12.9, 9.9, 8.7 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.2, 159.6, 153.0, 138.5, 129.2, 129.0, 127.5, 125.1, 120.7, 118.8, 116.0, 112.4, 112.3, 105.2, 101.6, 84.9, 78.3, 67.8, 66.9, 55.2, 49.6, 49.6, 33.3, 27.0. HRMS ESI: Calculated for C24H25O4 [M + H]+ 377.1753, found 377.1750 (Diff.: −0.74 ppm).
4.3.4. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(4-methoxyphenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4d
Compound 4d was prepared following the general procedure using compound 1d (49 mg, 0.160 mmol, 1 eq.), dihydrofuran (112 mg, 1.60 mmol, 10 eq.) and catalyst A (7 mg, 0.009 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4d (60%, 37 mg, 0.098 mmol) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.24 (dd, J = 7.6, 1.7 Hz, 1H), 7.12–7.03 (m, 3H), 6.88 (td, J = 7.5, 1.2 Hz, 1H), 6.79–6.70 (m, 2H), 6.63 (dd, J = 8.0, 1.2 Hz, 1H), 5.30 (d, J = 5.7 Hz, 1H), 4.78 (dd, J = 11.4, 1.3 Hz, 1H), 4.38 (dd, J = 11.4, 1.0 Hz, 1H), 4.32 (td, J = 8.4, 3.8 Hz, 1H), 4.08 (td, J = 8.5, 7.3 Hz, 1H), 3.85–3.72 (m, 6H), 3.40–3.32 (m, 1H), 2.74 (td, J = 9.5, 5.7 Hz, 1H), 2.46 (dtd, J = 12.8, 7.2, 3.7 Hz, 1H), 2.28 (dq, J = 12.8, 8.5 Hz, 1H), 2.06 (dddd, J = 12.9, 9.3, 7.3, 4.7 Hz, 1H), 1.85–1.66 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 208.9, 158.5, 152.9, 129.1, 128.9, 127.4, 127.4, 125.1, 120.6, 115.8, 113.7, 104.5, 101.4, 84.9, 78.0, 67.6, 66.8, 55.2, 49.8, 49.6, 33.1, 26.9. HRMS ESI: Calculated for C24H24NaO4 [M + Na]+ 399.1572, found 399.1551 (Diff.: 4.13 ppm).
4.3.5. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(3-fluorophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4e
Compound 4e was prepared following the general procedure using compound 1e (50 mg, 0.170 mmol, 1 eq.), dihydrofuran (119 mg, 1.70 mmol, 10 eq.) and catalyst A (7 mg, 0.009 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4e (65%, 41 mg, 0.11 mmol) as orange oil. 1H NMR (400 MHz, CDCl3) δ 7.28–7.22 (m, 1H), 7.18–7.05 (m, 2H), 6.96–6.86 (m, 2H), 6.85–6.75 (m, 2H), 6.60 (dd, J = 8.1, 1.2 Hz, 1H), 5.40 (d, J = 5.8 Hz, 1H), 4.87 (dd, J = 12.0, 1.3 Hz, 1H), 4.52 (d, J = 11.9 Hz, 1H), 4.31 (td, J = 8.4, 4.3 Hz, 1H), 4.09 (q, J = 8.1 Hz, 1H), 3.89–3.75 (m, 2H), 3.39 (dd, J = 8.1, 6.8 Hz, 1H), 2.79 (td, J = 9.4, 5.8 Hz, 1H), 2.50 (dtd, J = 12.8, 7.5, 4.2 Hz, 1H), 2.38–2.24 (m, 1H), 2.06 (dddd, J = 12.9, 9.3, 6.6, 5.5 Hz, 1H), 1.83–1.64 (m, 1H).13C NMR (101 MHz, CDCl3) δ 209.2, 162.8 (d, J = 244.9 Hz), 152.9, 139.4 (d, J = 7.6 Hz), 129.6 (d, J = 8.4 Hz), 129.1, 127.4, 125.2, 121.8 (d, J = 2.7 Hz), 120.9, 116.1, 113.6 (d, J = 21.2 Hz), 113.5 (d, J = 23.2 Hz), 104.9, 101.6, 84.9, 78.8, 67.8, 66.8, 49.5, 49.1, 33.1, 27.0. 19F NMR (376 MHz, CDCl3) δ −113.54–−113.72 (m). HRMS ESI: Calculated for C23H22FO3 [M + H]+ 365.1553, found 365.1546 (Diff.: 0.51 ppm).
4.3.6. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(3-bromophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4f
Compound 4f was prepared following the general procedure using compound 1f (53 mg, 0.149 mmol, 1 eq.), dihydrofuran (104 mg, 1.49 mmol, 10 eq.) and catalyst A (7 mg, 0.009 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4f (70%, 45 mg, 0.104 mmol) as an amorphous yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.24 (dd, J = 7.6, 1.7 Hz, 1H), 7.22–7.18 (m, 1H), 7.12 (q, J = 1.4 Hz, 1H), 7.10–7.00 (m, 3H), 6.89 (td, J = 7.5, 1.2 Hz, 1H), 6.57 (dd, J = 8.1, 1.2 Hz, 1H), 5.43 (d, J = 5.8 Hz, 1H), 4.89 (dd, J = 11.9, 1.5 Hz, 1H), 4.58 (dd, J = 12.0, 1.1 Hz, 1H), 4.29 (td, J = 8.4, 4.6 Hz, 1H), 3.78 (dd, J = 8.4, 6.1 Hz, 2H), 3.37 (tt, J = 7.2, 1.4 Hz, 1H), 2.79 (td, J = 9.4, 5.8 Hz, 1H), 2.55–2.42 (m, 1H), 2.27 (dtd, J = 12.8, 8.2, 7.0 Hz, 1H), 2.12–1.98 (m, 1H), 1.69 (ddt, J = 12.9, 9.7, 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.1, 152.9, 139.1, 129.6 (3C), 129.1, 127.2, 125.1, 124.8, 122.4, 121.0, 116.1, 105.0, 101.6, 84.9, 78.9, 67.8, 66.7, 49.4, 48.9, 32.9, 26.9. HRMS ESI: Calculated for C23H21BrNaO3 [M + Na]+ 447.0572, found 447.0567 (Diff.: −0.49 ppm).
4.3.7. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(3-chloro-4-fluorophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4g
Compound 4g was prepared following the general procedure using compound 1g (52 mg, 0.16 mmol, 1 eq.), dihydrofuran (112 mg, 1.6 mmol, 10 eq.) and catalyst A (8 mg, 0.010 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4g (44%, 28 mg, 0.070 mmol) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.27–7.21 (m, 1H), 7.05 (ddd, J = 8.1, 7.3, 1.7 Hz, 1H), 7.00–6.85 (m, 4H), 6.55 (dd, J = 8.0, 1.2 Hz, 1H), 5.48 (d, J = 5.9 Hz, 1H), 4.92 (dt, J = 11.9, 1.2 Hz, 1H), 4.66 (dt, J = 11.8, 1.2 Hz, 1H), 4.28 (td, J = 8.4, 5.1 Hz, 1H), 4.07 (td, J = 8.2, 7.1 Hz, 1H), 3.82–3.75 (m, 2H), 3.35 (ddt, J = 7.7, 6.2, 1.5 Hz, 1H), 2.82 (td, J = 9.4, 5.9 Hz, 1H), 2.52 (dtd, J = 12.8, 7.8, 5.1 Hz, 1H), 2.28 (dddd, J = 13.2, 8.4, 7.2, 6.1 Hz, 1H), 2.11–1.98 (m, 1H), 1.68 (ddt, J = 12.9, 9.5, 8.3 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 208.9, 156.9 (d, J = 256.6 Hz), 152.8, 134.0 (d, J = 3.3 Hz), 129.1, 128.7, 127.1, 125.9 (d, J = 7.1 Hz), 125.3, 121.1, 120.6 (d, J = 17.8 Hz), 116.1, 116.0 (d, J = 21.1 Hz), 104.8, 101.7, 84.8, 79.1, 67.9, 66.5, 49.2, 48.9, 32.8, 26.9. HRMS ESI: Calculated for C23H21ClFO3 [M + H]+ 399.1163, found 399.1165 (Diff.: −0.61 ppm).
4.3.8. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(4-bromo-3-fluorophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4h
Compound 4h was prepared following the general procedure using compound 1h (50 mg, 0.152 mmol, 1 eq.), dihydrofuran (106 mg, 1.52 mmol, 10 eq.) and catalyst A (6 mg, 0.008 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4h (46%, 24 mg, 0.070 mmol) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.32 (dd, J = 8.6, 7.3 Hz, 1H), 7.24 (dd, J = 7.5, 1.8 Hz, 1H), 7.07 (ddd, J = 8.1, 7.3, 1.7 Hz, 1H), 6.88 (td, J = 7.5, 1.2 Hz, 1H), 6.84–6.75 (m, 2H), 6.58 (dd, J = 8.1, 1.2 Hz, 1H), 5.45 (d, J = 5.9 Hz, 1H), 4.91 (dd, J = 12.1, 1.4 Hz, 1H), 4.59 (dd, J = 12.2, 1.0 Hz, 1H), 4.30 (td, J = 8.4, 4.7 Hz, 1H), 4.08 (q, J = 7.9 Hz, 1H), 3.78 (dd, J = 8.4, 6.1 Hz, 2H), 3.35 (t, J = 7.1 Hz, 1H), 2.81 (td, J = 9.3, 5.9 Hz, 1H), 2.51 (dtd, J = 12.5, 7.7, 4.7 Hz, 1H), 2.27 (dq, J = 12.9, 7.6 Hz, 1H), 2.05 (ddt, J = 12.7, 9.4, 6.1 Hz, 1H), 1.69 (dq, J = 13.0, 8.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.1, 158.8 (d, J = 246.4 Hz), 152.9, 138.6 (d, J = 6.9 Hz), 132.9 (d, J = 1.0 Hz), 129.2, 127.3, 125.4, 122.9 (d, J = 3.2 Hz), 121.1, 116.2, 114.5 (d, J = 23.5 Hz), 106.8 (d, J = 21.2 Hz), 104.86 (d, J = 2.2 Hz), 101.7, 84.9, 79.3, 67.9, 66.6, 49.4, 48.7, 32.9, 27.0. HRMS ESI: Calculated for C23H20BrFNaO3 [M + Na]+ 465.0478, found 465.0464 (Diff.: 0.65 ppm).
4.3.9. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(4-chlorophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4i
Compound 4i was prepared following the general procedure using compound 1i (50 mg, 0.161 mmol, 1 eq.), dihydrofuran (113 mg, 1.61 mmol, 10 eq.) and catalyst A (8 mg, 0.010 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4i (28%, 17 mg, 0.045 mmol) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.25 (dd, J = 7.6, 1.7 Hz, 1H), 7.16–7.11 (m, 2H), 7.09–7.01 (m, 3H), 6.88 (td, J = 7.5, 1.2 Hz, 1H), 6.59 (dd, J = 8.1, 1.2 Hz, 1H), 5.38 (d, J = 5.8 Hz, 1H), 4.86 (dd, J = 11.9, 1.4 Hz, 1H), 4.51 (dd, J = 11.9, 1.1 Hz, 1H), 4.31 (td, J = 8.4, 4.3 Hz, 1H), 4.08 (q, J = 8.0 Hz, 1H), 3.84–3.73 (m, 2H), 3.37 (tt, J = 7.3, 1.3 Hz, 1H), 2.78 (td, J = 9.4, 5.8 Hz, 1H), 2.50 (dtd, J = 12.7, 7.5, 4.3 Hz, 1H), 2.28 (dtd, J = 12.8, 8.3, 7.4 Hz, 1H), 2.05 (dddd, J = 12.9, 9.3, 6.7, 5.4 Hz, 1H), 1.79–1.60 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 209.1, 152.9, 135.4, 132.4, 129.1, 128.4, 127.7, 127.4, 125.3, 121.0, 116.2, 104.9, 101.6, 84.9, 78.7, 67.9, 66.8, 49.5, 49.1, 33.1, 27.0. HRMS ESI: Calculated for C23H22ClO3 [M + H]+ 381.1257, found 381.1255 (Diff.: −0.64 ppm).
4.3.10. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(4-(trifluoromethyl)phenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4j
Compound 4j was prepared following the general procedure using compound 1j (50 mg, 0.145 mmol, 1 eq.), dihydrofuran (102 mg, 1.45 mmol, 10 eq.) and catalyst A (6 mg, 0.007 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4j (44%, 26 mg, 0.064 mmol) as an amorphous yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.42–7.36 (m, 2H), 7.30–7.23 (m, 1H), 7.19 (d, J = 8.1 Hz, 2H), 7.03 (ddd, J = 8.0, 7.3, 1.7 Hz, 1H), 6.87 (td, J = 7.5, 1.2 Hz, 1H), 6.53 (dd, J = 8.1, 1.2 Hz, 1H), 5.43 (d, J = 6.0 Hz, 1H), 5.02–4.82 (m, 1H), 4.62 (d, J = 12.1 Hz, 1H), 4.31 (td, J = 8.4, 4.7 Hz, 1H), 4.10 (q, J = 8.0 Hz, 1H), 3.91–3.68 (m, 2H), 3.57–3.35 (m, 1H), 2.82 (td, J = 9.4, 5.9 Hz, 1H), 2.54 (dtd, J = 12.6, 7.7, 4.7 Hz, 1H), 2.44–2.23 (m, 1H), 2.13–1.97 (m, 1H), 1.69 (ddt, J = 12.9, 9.5, 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.6, 152.9, 140.7, 129.2, 128.7 (q, J = 32.4 Hz), 127.3, 126.6, 125.4, 125.1 (q, J = 3.8 Hz), 124.4 (q, J = 273.7 Hz), 121.1, 116.3, 105.3, 101.7, 85.0, 79.0, 67.9, 66.7, 49.4, 48.7, 33.0, 27.0. 19F NMR (376 MHz, CDCl3) δ–62.48 (s). HRMS ESI: Calculated for C24H21F3NaO3 [M + Na]+ 437.1340, found 437.1336 (Diff.: −0.31 ppm).
4.3.11. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(4-nitrophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4k
Compound 4k was prepared following the general procedure using compound 1k (50 mg, 0.205 mmol, 1 eq.), dihydrofuran (167 mg, 2.05 mmol, 10 eq.) and catalyst A (9 mg, 0.012 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4k (60%, 48 mg, 0.12 mmol) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 9.0 Hz, 2H), 7.26 (dd, J = 7.5, 1.7 Hz, 1H), 7.20 (d, J = 8.9 Hz, 2H), 7.06–6.97 (m, 1H), 6.86 (td, J = 7.5, 1.2 Hz, 1H), 6.49 (dd, J = 8.0, 1.2 Hz, 1H), 5.52 (d, J = 6.1 Hz, 1H), 5.04 (dd, J = 12.7, 1.6 Hz, 1H), 4.79 (dd, J = 12.7, 1.2 Hz, 1H), 4.31 (td, J = 8.5, 5.3 Hz, 1H), 4.09 (td, J = 8.4, 6.9 Hz, 1H), 3.77 (ddd, J = 8.5, 6.2, 3.4 Hz, 2H), 3.63–3.45 (m, 1H), 2.88 (td, J = 9.3, 6.1 Hz, 1H), 2.59 (dtd, J = 13.1, 8.0, 5.3 Hz, 1H), 2.40–2.28 (m, 1H), 2.04 (dddd, J = 12.6, 9.4, 7.2, 5.2 Hz, 1H), 1.69 (dq, J = 13.1, 8.6 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 210.0, 152.7, 146.2, 143.7, 129.2, 127.2, 126.9, 125.6, 123.3, 121.3, 116.3, 105.8, 101.8, 84.8, 79.6, 67.9, 66.4, 49.1, 47.9, 32.7, 26.9. HRMS ESI: Calculated for C23H21NNaO5 [M + Na]+ 414.1317, found 414.1309 (Diff.: 0.35 ppm).
4.3.12. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(3-nitrophenyl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4l
Compound 4l was prepared following the general procedure using compound 1l (51 mg, 0.159 mmol, 1 eq.), dihydrofuran (111 mg, 1.59 mmol, 10 eq.) and catalyst A (8 mg, 0.010 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4l (34%, 21 mg, 0.054 mmol) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 7.90 (ddd, J = 8.0, 2.3, 1.2 Hz, 1H), 7.81 (t, J = 2.0 Hz, 1H), 7.34 (dt, J = 7.8, 1.5 Hz, 1H), 7.31–7.23 (m, 2H), 7.04–6.92 (m, 1H), 6.87 (td, J = 7.4, 1.3 Hz, 1H), 6.42 (dd, J = 8.0, 1.3 Hz, 1H), 5.53 (d, J = 6.0 Hz, 1H), 5.03 (dd, J = 12.2, 1.7 Hz, 1H), 4.83 (dd, J = 12.3, 1.4 Hz, 1H), 4.30 (td, J = 8.4, 5.5 Hz, 1H), 4.10 (td, J = 8.4, 6.8 Hz, 1H), 3.84–3.70 (m, 2H), 3.51 (ddt, J = 7.2, 5.4, 1.6 Hz, 1H), 2.88 (td, J = 9.3, 6.0 Hz, 1H), 2.68–2.50 (m, 1H), 2.43–2.28 (m, 1H), 2.04 (dddd, J = 12.7, 9.4, 7.3, 5.0 Hz, 1H), 1.76–1.60 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 209.2, 152.8, 148.1, 138.7, 132.3, 129.1, 128.8, 127.1, 125.6, 125.5, 121.4, 121.3, 116.2, 105.5, 101.8, 84.9, 79.7, 68.0, 66.5, 49.1, 48.3, 32.6, 26.9. HRMS ESI: Calculated for C23H21NNaO5 [M + Na]+ 414.1317, found 414.1296 (Diff.: 4.40 ppm).
4.3.13. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(thiophen-2-yl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4m
Compound 4m was prepared following the general procedure using compound 1m (50 mg, 0.177 mmol, 1 eq.), dihydrofuran (124 mg, 1.77 mmol, 10 eq.) and catalyst A (7 mg, 0.09 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4m (65%, 41 mg, 0.117 mmol) as an amorphous yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.24 (dd, J = 7.6, 1.7 Hz, 1H), 7.15–7.05 (m, 2H), 6.93–6.79 (m, 3H), 6.66 (dd, J = 8.1, 1.2 Hz, 1H), 5.54 (d, J = 5.7 Hz, 1H), 4.89 (d, J = 12.3 Hz, 1H), 4.48 (dd, J = 12.3, 0.9 Hz, 1H), 4.30 (td, J = 8.5, 3.9 Hz, 1H), 4.14–4.00 (m, 1H), 3.92–3.75 (m, 2H), 3.42–3.25 (m, 1H), 2.83 (td, J = 9.5, 5.7 Hz, 1H), 2.47 (dtd, J = 12.8, 7.4, 3.9 Hz, 1H), 2.25 (dq, J = 12.8, 8.4 Hz, 1H), 2.08 (dddd, J = 12.8, 9.2, 7.2, 4.9 Hz, 1H), 1.72 (ddt, J = 12.9, 9.8, 8.5 Hz, 1H).13C NMR (101 MHz, CDCl3) δ 208.4, 153.0, 141.3, 129.1, 127.5, 127.3, 124.9, 124.5, 123.0, 120.8, 116.1, 101.7, 100.8, 84.9, 79.5, 67.8, 66.8, 51.1, 49.6, 32.9, 27.1. HRMS ESI: Calculated for C21H21SO3 [M + H]+ 353.1211, found 353.1196 (Diff.: 2.77 ppm).
4.3.14. Synthesis of (2S,3R,3a′R,9a′S)-3-(1-(benzo[b]thiophen-2-yl)propa-1,2-dien-1-yl)-2′,3′,3a′,4,5,9a′-hexahydro-3H-spiro[furan-2,4′-furo[2,3-b]chromene] 4n
Compound 4i was prepared following the general procedure using compound 1i (50 mg, 0.150 mmol, 1 eq.), dihydrofuran (105 mg, 1.50 mmol, 10 eq.) and catalyst A (6 mg, 0.008 mmol, 0.05 eq.) in 1,4-dioxane (1 mL). Purification by chromatography on silica gel (8/2 pentane/Et2O) afforded compound 4i (68%, 41 mg, 0.102 mmol) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 7.7–7.6 (m, 2H), 7.3–7.2 (m, 3H), 7.2–7.0 (m, 2H), 6.9 (td, J = 7.5, 1.2 Hz, 1H), 6.7 (dd, J = 8.0, 1.2 Hz, 1H), 5.6 (d, J = 5.8 Hz, 1H), 5.0 (dt, J = 12.8, 1.1 Hz, 1H), 4.5 (dt, J = 12.8, 1.0 Hz, 1H), 4.3 (td, J = 8.5, 3.6 Hz, 1H), 4.1 (td, J = 8.6, 7.5 Hz, 1H), 4.0–3.7 (m, 2H), 3.4 (dd, J = 8.4, 7.1 Hz, 1H), 2.9 (td, J = 9.4, 5.8 Hz, 1H), 2.5 (dtd, J = 12.8, 7.3, 3.6 Hz, 1H), 2.4–2.2 (m, 1H), 2.2–2.0 (m, 1H), 1.7 (ddt, J = 12.9, 9.7, 8.4 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 209.3, 153.0, 141.9, 140.4, 139.4, 129.2, 127.5, 125.2, 124.3, 124.2, 123.3, 122.0, 121.0, 119.2, 116.3, 101.9, 101.4, 85.0, 80.0, 67.8, 66.8, 50.1, 49.7, 33.0, 27.2. HRMS ESI: Calculated for C25H23SO3 [M + H]+ 403.1368, found 403.1354 (Diff.: 1.64 ppm).
Procedures for the synthesis of the substrates and the products and full characterization of final products can be found in the
Supplementary Materials.