Novel Route for the Construction of Chroman Ring System Using Cross-Coupling between Benzylic and Aliphatic Alcohols in the Presence of NaHSO₄/SiO₂

Abstract

Novel route for the construction of chromans from benzylic and aliphatic alcohols in the presence of NaHSO₄/SiO₂ has been developed. In this reaction, substituted olefins are formed from benzylic and aliphatic alcohols and then converted to chromans through intramolecular cyclization. Twenty novel chromans were synthesized by this simple procedure.

Key words

chroman - tandem reaction - heterogeneous reaction - coupling reaction - solid acid

• References and Notes

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• 19 Melting points were determined on Büchi Melting Point B-540 apparatus. NMR spectra were recorded on a JEOL ECX 400 spectrometer. Tetramethylsilane (δ = 0 ppm) was used as an internal standard for ¹H NMR and CDCl₃ (δ = 77.0 ppm) for ¹³C NMR measurements. Mass analyses were performed on an Agilent G1969 LC/MDS TOF instrument. IR spectra were recorded on a JASCO FT/IR-6100 equipment. Elemental analyses were performed on a J Science Lab. microcorder JM-10 instrument. Preparation of NaHSO₄/SiO₂ : SiO₂ [Wakogel C-200 (Wako Pure Chemical Ind. Ltd.), 10 g] was added to a solution of ­NaHSO₄·H₂O (30 mmol, 4.14 g) in distilled H₂O, and the mixture was stirred at r.t. for 0.5 h. The H₂O was removed by rotary evaporator under reduced pressure, and the resulting reagent was dried in vacuo (10 mmHg) at 120 °C for 5 h. Typical Procedure: A mixture of 1 (2 mmol), 2 (4 or 15 mmol) and NaHSO₄/SiO₂ (2.1 mmol/g, 1.0 or 2.0 g) in DCE (10 mL) was stirred at 80 °C for 2 h, and then the used supported reagent was removed by filtration. The filtrate was evaporated to leave crude product, which was purified by column chromatography (hexane–CHCl₃) to obtain substituted chromans 3. 6-Methyl-2,2,4-triphenylchroman (3bb): yield: 0.7315 g (97%); white solid; mp 173–175 °C (MeOH). ¹H NMR (400 MHz, CDCl₃): δ = 2.08 (s, 3 H), 2.60 (dd, J = 13.9, 12.6 Hz, 1 H), 3.06 (dd, J = 13.9, 5.4 Hz, 1 H), 3.86 (dd, J = 12.6, 5.4 Hz, 1 H), 6.42 (s, 1 H), 6.95 (dd, J = 8.2, 2.3 Hz, 1 H), 7.03 (d, J = 8.2 Hz, 1 H), 7.18–7.34 (m, 11 H), 7.47–7.52 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 20.5, 40.1, 42.2, 81.6, 117.0, 124.8, 125.6, 126.3, 126.7, 127.0, 127.3, 128.2, 128.5, 128.6 (overlap), 128.8, 129.5, 129.7, 143.5, 144.5, 145.8, 152.0. IR (neat): 3057, 2920, 1591, 1487, 1445, 1283, 1231, 1110, 1061, 1007, 920, 846, 805, 784, 748, 732, 695, 628, 585, 539 cm^–1. HRMS (TOF–CI): m/z [M + H]⁺ calcd for C₂₈H₂₅O: 377.1905; found: 377.1896. Anal. Calcd for C₂₈H₂₄O: C, 89.33; H, 6.43. Found: C, 89.58; H, 6.15. 6-Methoxy-2,2,4-triphenylchroman (3cb): yield: 0.7534 g (96%); white solid; mp 106–108 °C (MeOH). ¹H NMR (400 MHz, CDCl₃): δ = 2.59 (dd, J = 13.9, 12.6 Hz, 1 H), 3.08 (dd, J = 13.9, 5.4 Hz, 1 H), 3.52 (s, 3 H), 3.87 (dd, J = 12.6, 5.4 Hz, 1 H), 6.15 (d, J = 3.0 Hz, 1 H), 6.73 (dd, J = 8.9, 3.0 Hz, 1 H), 7.07 (d, J = 8.9 Hz, 1 H), 7.17–7.33 (m, 11 H), 7.47–7.52 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 40.4, 42.0, 55.4, 81.5, 113.8, 114.1, 117.8, 125.6, 125.8, 126.3, 126.8, 127.0, 127.2, 128.2, 128.6, 128.6, 128.8, 143.4, 144.2, 145.8, 148.2, 153.2. IR (neat): 3055, 2827, 1604, 1489, 1451, 1417, 1252, 1211, 1155, 1100, 1036, 950, 912, 859, 809, 755, 698, 588, 512 cm^–1. HRMS (TOF–CI): m/z [M⁺] calcd for C₂₈H₂₄O₂: 392.1776; found: 392.1777. Anal. Calcd for C₂₈H₂₄O₂: C, 85.68; H, 6.16. Found: C, 85.77; H, 6.16. 6-Bromo-2,2,4-triphenylchroman (3db): yield: 0.8474 g (96%); white solid; mp 158–160 °C (MeOH). ¹H NMR (400 MHz, CDCl₃): δ = 2.59 (dd, J = 14.0, 12.7 Hz, 1 H), 3.08 (dd, J = 14.0, 5.5 Hz, 1 H), 3.85 (dd, J = 12.7, 5.5 Hz, 1 H), 6.74 (d, J = 2.3 Hz, 1 H), 7.02 (d, J = 8.7 Hz, 1 H), 7.15–7.35 (m, 12 H), 7.45–7.48 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 40.1, 41.6, 82.2, 112.7, 119.1, 125.6, 126.1, 127.1, 127.3, 127.5, 127.6, 128.3, 128.7, 128.7, 128.8, 130.8, 132.1, 143.0, 143.4, 145.2, 153.3. IR (neat): 3056, 1592, 1469, 1396, 1240, 1203, 1110, 1062, 1007, 915, 877, 842, 811, 777, 754, 694, 585, 542 cm^–1. HRMS (TOF–CI): m/z [M⁺] calcd for C₂₇H₂₁BrO: 440.0775; found: 440.0776. Anal. Calcd for C₂₇H₂₁BrO: C, 73.48; H, 4.80. Found: C, 73.68; H, 4.71. 7-Methoxy-2,2,4-triphenylchroman (3eb): yield: 0.6579 g (83%); white solid; mp 148–149 °C (MeOH). ¹H NMR (400 MHz, CDCl₃): δ = 2.59 (dd, J = 13.8, 12.6 Hz, 1 H), 3.07 (dd, J = 13.8, 5.4 Hz, 1 H), 3.78 (s, 3 H), 3.88 (dd, J = 12.6, 5.4 Hz, 1 H), 6.33 (dd, J = 8.6, 2.6 Hz, 1 H), 6.51 (d, J = 8.6 Hz, 1 H), 6.70 (d, J = 2.6 Hz, 1 H), 7.16–7.35 (m, 11 H) 7.47–7.52 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 39.5, 42.2, 55.3, 82.1, 101.7, 107.4, 117.6, 125.7, 126.3, 126.7, 127.1, 127.3, 128.2, 128.6 (overlap), 128.7, 130.2, 143.4, 144.6, 145.6, 155.0, 159.3. IR (neat): 2969, 1611, 1580, 1495, 1444, 1410, 1318, 1258, 1195, 1158, 1101, 1058, 1033, 1018, 966, 910, 835, 772, 734, 696, 627, 594, 556, 518 cm^–1. HRMS (TOF–CI): m/z [M + H]⁺ calcd for C₂₈H₂₅O₂: 393.1854; found: 393.1851. Anal. Calcd for C₂₈H₂₄O₂: C, 85.68; H, 6.16. Found: C, 85.88; H, 6.02. 6,8-Dibromo-2,2,4-triphenylchroman (3gb): yield: 1.0283 g (98%); white solid; mp 166–167 °C (EtOH). ¹H NMR (400 MHz, CDCl₃): δ = 2.55 (dd, J = 14.1, 12.6 Hz, 1 H), 3.21 (dd, J = 14.1, 5.5 Hz, 1 H), 3.93 (dd, J = 14.1, 12.6 Hz, 1 H), 6.69 (d, J = 2.4 Hz, 1 H), 7.13–7.35 (m, 11 H), 7.48–7.60 (m, 5 H). ¹³C NMR (100 MHz, CDCl₃): δ = 40.3, 41.2, 83.4, 112.5, 112.6, 125.0, 125.6, 127.3, 127.4, 127.5, 128.4, 128.6, 128.9, 129.0 (overlap), 131.4, 133.6, 142.7, 142.9, 144.9, 149.8. IR (neat): 3074, 3032, 1490, 1440, 1248, 1153, 1114, 1058, 1015, 941, 862, 771, 741, 695, 582 cm^–1. HRMS (TOF–CI): m/z [M⁺] calcd for C₂₇H₂₀Br₂O: 517.9880; found: 517.9872. Anal. Calcd for C₂₇H₂₀Br₂O: C, 62.33; H, 3.87. Found: C, 62.45; H, 3.77. 6-Bromo-4-methyl-2,2-diphenylchroman (3jb): yield: 0.7257 g (95%); white solid; mp 146–147 °C. ¹H NMR (400 MHz, CDCl₃): δ = 1.32 (d, J = 6.8 Hz, 3 H), 2.15 (dd, J = 13.7, 12.2 Hz, 1 H), 2.67–2.77 (m, 1 H), 2.87 (dd, J = 13.7, 5.3 Hz, 1 H), 6.93–6.96 (m, 1 H), 7.18–7.33 (m, 8 H), 7.39–7.45 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 19.8, 26.7, 41.0, 82.0, 112.7, 119.0, 125.7, 126.3, 127.1, 127.4, 128.2, 128.5, 129.1, 129.8, 130.3, 143.2, 145.6, 152.7. IR (neat): 3058, 2871, 1572, 1473, 1397, 1321, 1218, 1180, 1122, 1094, 1056, 982, 899, 824, 761, 727, 696, 670, 603, 512 cm^–1. HRMS (TOF–CI): m/z [M⁺] calcd for C₂₂H₁₉BrO: 378.0619; found: 378.0620. Anal. Calcd for C₂₂H₁₉BrO: C, 69.67; H, 5.05. Found: C, 69.65; H, 5.07.