(1R,2'S)-1-(5-Methoxy-2,7-dimethylchroman-2-yl)-ethan-1,2-diol (anti-242) and (1S,2'S)-1-(5-methoxy-2,7-dimethylchroman-2-yl)-ethan-1,2-diol (syn-242)
A solution of vinyl chromane (S)-101 (2.93 g, 13.4 mmol, 1.00 eq.) in tBuOH/H2O (60 mL/60 mL) was treated with AD-mix α (28.2 g) and MeSO2NH2 (1.29 g, 13.4 mmol, 1.00 eq.) at RT. After being stirred for 5 d the reaction was quenched by addition of sat. aq.
NaHSO3 solution (100 mL) at 0 °C and stirring continued at 0 °C for 30 min. The aq. layer was extracted with EtOAc (4 × 100 mL), the combined organic layers were dried over Na2SO4 and concentrated in vacuo. After column chromatography on silica gel (petroleum ether/EtOAc = 6:4) and preparative HPLC (Daicel Chiralcel IB®: 10 × 250 mm, 5 µm, n-hexane/iPrOH = 97:3, 5 mL/min, λ = 210 nm) the diols anti-242 (2.48 g, 9.81 mmol) and syn-242 (654 mg, 2.59 mmol) were obtained as colorless oils (3.13 g, 12.4 mmol, 93%, d.r. = 3.8:1).
160 Experimental Section
Analytical HPLC (Daicel Chiralpak IB®, 4.6 × 250 mm, 5 m, n-hexane/2-PrOH = 97:3, 0.8 mL/min): tR = 25.6 min.
Preparative HPLC (Daicel Chiralpak IB®, 20 × 250 mm, 7 m, n-hexane/2-PrOH = 97:3, 5 mL/min, 210 nm): tR = 26.1 min.
MS (ESI): m/z (%) = 527.3 (100) [2M+Na]+, 275.1 (15) [M+Na]+, 253.2 (2) [M+H]+.
C14H20O4 (252.31) calc.: 275.1254
found: 275.1256 [M+Na]+ (ESI-HRMS).
Analytical data of diol syn-242:
Optical Rotation: [α]D = +20.6 (c = 0.50, CHCl3, 26.7 °C).
1H-NMR (300 MHz, CDCl3): (ppm) = 1.21 (s, 3 H, 2'-CH3), 1.74 (ddd, J = 13.7, 6.5, 4.1 Hz, 1 H, 3'-Ha), 1.82–2.01 (m, 1 H, 3'-Hb), 2.25 (s, 3 H, 7'-CH3), 2.50 (ddd, J = 17.3, 10.3, 6.6 Hz, 1 H, 4'-Ha), 2.71 (dt, J = 17.2, 5.9 Hz, 1 H, 4'-Hb), 2.79 (sbr, 1 H, OH), 3.69–3.77 (m, 3 H, 1-H, 2-H2), 3.78 (s, 3 H, 5'-OCH3), 6.23, 6.28 (2 × s, 2 H, 6'-H, 8'-H).
13C-NMR (150 MHz, CDCl3): (ppm) = 15.8 (C-4'), 18.6 (2'-CH3), 21.6 (7'-CH3), 27.5 (C-3'), 55.3 (5'-OCH3), 62.5 (C-2), 76.4 (C-1), 77.5 (C-2'), 103.1, 110.2 (C-6', C-8'), 107.0 (C-4a'), 137.2 (C-7'), 153.0, 157.5 (C-5', C-8a').
IR: 𝜈 ̃(cm-1) = 3383, 2933, 1617, 1584, 1455, 1414, 1351, 1227, 1159, 1139, 1104, 1079, 1024, 875, 812, 581.
UV (CH3CN): max (nm) (lg ) = 208 (4.610), 272 (2.961), 280 (2.942).
Analytical HPLC (Daicel Chiralpak IB®, 4.6 × 250 mm, 5 m, n-hexane/2-PrOH = 97:3, 0.8 mL/min): tR = 36.0 min.
Preparative HPLC (Daicel Chiralpak IB®, 20 × 250 mm, 7 m, n-hexane/2-PrOH = 97:3, 5 mL/min, 210 nm): tR = 36.3 min.
MS (ESI): m/z (%) = 527.3 (100) [2M+Na]+, 275.1 (9) [M+Na]+.
C14H20O4 (252.31) calc.: 275.1254
found: 275.1254 [M+Na]+ (ESI-HRMS).
Enantioselective Total Synthesis of (–)-Diversonol 161
3.4.2 (1R,2'S)-1,2-Bis-(tert-butyldimethylsilyloxy)-2-(5-methoxy-2,7-dimethylchroman-2-yl)-ethane (anti-243)
A solution of diol anti-242 (1.34 g, 5.31 mmol, 1.00 eq.) in CH2Cl2 (50 mL) was treated with 2,6-lutidine (2.47 mL, 21.2 mmol, 4.00 eq.) and TBSOTf (4.27 mL, 18.6 mmol, 3.50 eq.) at 0 °C. After stirring at RT for 2.5 h, the reaction was quenched by careful addition of sat. aq.
NaHCO3 solution (50 mL) at 0 °C. The aq. layer was extracted with CH2Cl2 (3 × 25 mL), the combined organic extracts dried over MgSO4 and the solvent removed in vacuo. After column chromatography on silica gel (petroleum ether/MTBE = 40:1) alcohol anti-243 was obtained as a colorless oil (2.52 g, 5.24 mmol, 99%).
Optical Rotation: []D = +17.9 (c = 0.51, CHCl3, 24.7 °C).
1H-NMR (600 MHz, CDCl3): (ppm) = 0.00, 0.02, 0.04, 0.11 (4 × s, 12 H, 1-Si(CH3)2, 2-Si(CH3)2), 0.87 (s, 18 H, 1-SiC(CH3)3, 2-SiC(CH3)3), 1.15 (s, 3 H, 2'-CH3), 1.70 (dt, J = 13.6, 6.2 Hz, 1 H, 3'-Ha), 1.95 (ddd, J = 13.6, 8.5, 6.3 Hz, 1 H, 3'-Hb), 2.24 (s, 3 H, 7'-CH3), 2.47–2.52 (m, 1 H, 4'-Ha), 2.58 (dt, J = 17.3, 6.2 Hz, 1 H, 4'-Hb), 3.58 (dd, J = 10.6, 6.7 Hz, 1 H, 1-Ha), 3.67 (dd, J = 6.7, 2.2 Hz, 1 H, 2-H), 3.78 (s, 3 H, 5'-OCH3), 3.98 (dd, J = 10.6, 2.2 Hz, 1 H, 1-Hb), 6.19, 6.22 (2 × s, 2 H, 6'-H, 8'-H).
13C-NMR (150 MHz, CDCl3): (ppm) = –5.4, –5.3, –4.9, –3.9 (1-Si(CH3)2, 2-Si(CH3)2), 15.8 (C-4'), 18.3, 18.5 (1-SiC, 2-SiC), 19.6 (2'-CH3), 21.6 (7'-CH3), 26.0, 26.1 (1-SiC(CH3)3, 2-SiC(CH3)3), 27.6 (C-3'), 55.3 (5'-OCH3), 65.2 (C-1), 77.4 (C-2'), 78.0 (C-2), 102.5, 110.3 (C-6', C-8'), 107.2 (C-4a'), 136.7 (C-7'), 153.9, 157.4 (C-5', C-8a').
IR: 𝜈 ̃(cm-1) = 2953, 2928, 2855, 1619, 1586, 1462, 1352, 1276, 1256, 1110, 1091, 1067, 1005, 965, 829, 811, 770, 747, 664.
UV (CH3CN): max (nm) (lg ) = 208 (4.645), 272 (3.242), 280 (3.225).
MS (ESI): m/z (%) = 503.3 (100) [M+Na]+, 481.3 (38) [M+H]+. C26H48O4Si2 (480.83) calc.: 503.2983
found: 503.2983 [M+Na]+ (ESI-HRMS).
162 Experimental Section
3.4.3 (1S,2'S)-1,2-(Bis-tert-butyldimethylsilyloxy)-2-(5-methoxy-2,7-dimethylchroman-2-yl)-ethane (syn-243)
A solution of diol syn-242 (638 mg, 2.53 mmol, 1.00 eq.) in CH2Cl2 (25 mL) was treated with 2,6-lutidine (1.18 mL, 10.1 mmol, 4.00 eq.) and TBSOTf (2.03 mL, 8.85 mmol, 3.50 eq.) at 0 °C. After stirring at RT for 2.5 h, the reaction mixture was quenched by careful addition of sat. aq. NaHCO3 solution (30 mL) at 0 °C. The aq. layer was extracted with EtOAc (3 × 20 mL), the combined organic extracts were dried over MgSO4 and the solvent removed in vacuo. After column chromatography on silica gel (petroleum ether/MTBE = 40:1), syn-243 was obtained as a colorless oil (1.22 g, 2.53 mmol, quant.).
Optical Rotation: []D = +0.4 (c = 0.50, CHCl3, 24.6 °C).
1H-NMR (600 MHz, CDCl3): (ppm) = 0.04, 0.05, 0.09, 0.10 (4 × s, 12 H, 1-Si(CH3)2, 2-Si(CH3)2), 0.89, 0.91 (2 × s, 18 H, 1-SiC(CH3)3, 2-SiC(CH3)3) 1.21 (s, 3 H, 2'-CH3), 1.62 (ddd, J = 13.4, 11.1, 6.0 Hz, 1 H, 3'-Ha), 1.84 (ddd, J = 13.6, 6.1, 3.5 Hz, 1 H, 3'-Hb), 2.26 (s, 3 H, 7'-CH3), 2.44 (ddd, J = 17.3, 11.2, 6.2 Hz, 1 H, 4'-Ha), 2.67 (ddd, J = 17.0, 5.6, 3.7 Hz, 1 H, 4'-Hb), 3.54 (dd, J = 10.6, 6.0 Hz, 1 H, 1-Ha), 3.71 (dd, J = 5.9, 3.3 Hz, 1 H, 2-H), 3.78 (s, 3 H, 5'-OCH3), 3.82 (dd, J = 10.5, 3.3 Hz, 1 H, 1-Hb), 6.20, 6.26 (2 × s, 2 H, 6'-H, 8'-H).
13C-NMR (150 MHz, CDCl3): (ppm) = –5.3, –5.3, –4.7, –4.1 (1-Si(CH3)2, 2-Si(CH3)2), 16.1 (C-4'), 18.4, 18.5 (SiC), 19.6 (2'-CH3), 21.7 (7'-CH3), 26.1 (1-SiC(CH3)3, 2-SiC(CH3)3), 26.6 (C-3'), 55.4 (5'-OCH3), 65.3 (C-1), 78.0 (C-2'), 79.5 (C-2), 102.4, 110.3 (C-6', C-8'), 107.3 (C-4a'), 136.9 (C-7'), 153.8, 157.5 (C-5', C-8a').
IR: 𝜈 ̃(cm-1) = 2953, 2928, 2855, 1618, 1586, 1462, 1352, 1252, 1137, 1109, 1059, 1003, 830, 811, 774, 663.
UV (CH3CN): max (nm) (lg ) = 208 (4.621), 273 (2.907), 280 (2.887).
MS (ESI): m/z (%) = 503.3 (100) [M+Na]+, 481.3 (16) [M+H]+. C26H48O4Si2 (480.8279) calc.: 503.2983
found: 503.2982 [M+Na]+ (ESI-HRMS).
Enantioselective Total Synthesis of (–)-Diversonol 163
3.4.4 (2R,2'S)-2-(tert-Butyldimethylsilyloxy)-2-(5-methoxy-2,7-dimethylchroman-2-yl)ethanol (anti-244)
A solution of anti-243 (1.61 g, 3.35 mmol, 1.00 eq.) in THF (140 mL) and pyridine (17 mL) was treated with HF∙pyridine (3.36 mL, 70% HF, 134 mmol, 40.0 eq.) at 0 °C and the resulting mixture stirred at RT. After 24 and 48 h additional HF∙pyridine (1.68 mL, 70% HF, 67.0 mmol, 20.0 eq.) in THF/pyridine (70 mL/17 mL) was added at 0 °C. The reaction was quenched carefully with sat. aq. NaHCO3 solution (250 mL) at 0 °C after 60 h. The aq. layer was extracted with EtOAc (3 × 100 mL), the combined organic extracts were washed with brine (100 mL), dried over Na2SO4 and the solvent was removed in vacuo. Column chromatography on silica gel (petroleum ether/MTBE = 100:0 → 50:50) yielded alcohol anti-244 as a colorless oil (858 mg, 2.31 mmol, 70%, 93% brsm).
Optical Rotation: []D = +6.8 (c = 0.50, CHCl3, 25.0 °C).
164 Experimental Section quenched carefully with sat. aq. NaHCO3 solution (250 mL) at 0 °C after 52 h. The aq. layer was extracted with EtOAc (3 × 100 mL), the combined organic extracts were dried over Na2SO4 and the solvent was removed in vacuo. Column chromatography on silica gel (petroleum ether/EtOAc = 100:0 → 50:50) yielded alcohol syn-244 as a colorless oil (753 mg, 2.05 mmol, 73%, 98% brsm).
Enantioselective Total Synthesis of (–)-Diversonol 165
3.4.6 (2S,2'S)-2-(tert-Butyldimethylsilyloxy)-2-(5-methoxy-2,7-dimethylchroman-2-yl)-acetaldehyde (anti-245)
A solution of alcohol anti-244 (1.15 g, 3.14 mmol, 1.00 eq.) in CH2Cl2 (30 mL) was treated with DMP (2.33 g, 5.49 mmol, 1.75 eq.) at 0 °C and the reaction mixture stirred at RT for 2 h.
The reaction was quenched by addition of sat. aq. NaHCO3 solution (20 mL) and H2O (50 mL) at 0 °C. The aq. layer was extracted with CH2Cl2 (3 × 25 mL) and the combined organic phases were dried over Na2SO4. After evaporation of the organic solvents and column chromatography on silica gel (petroleum ether/EtOAc = 20:1) aldehyde anti-245 was obtained as a colorless oil (1.08 g, 2.97 mmol, 95%).
Optical Rotation: []D = +57.7 (c = 0.51, CHCl3, 26.3 °C).
1H-NMR (600 MHz, CDCl3): (ppm) = 0.02 (s, 3 H, Si(CH3)a), 0.09 (s, 3 H, Si(CH3)b), 0.91 (s, 9 H, SiC(CH3)3), 1.26 (s, 3 H, 2'-CH3), 1.72 (dt, J = 13.5, 6.6 Hz, 1 H, 3'-Ha), 2.04 (dt, J = 13.8, 7.0 Hz, 1 H, 3'-Hb), 2.26 (s, 3 H, 7'-CH3), 2.59 (t, J = 6.8 Hz, 2 H, 4'-H2), 3.79 (s, 3 H, 5'-OCH3), 4.11 (d, J = 1.0 Hz, 1 H, 2-H), 6.24, 6.29 (2 × s, 2 H, 6'-H, 8'-H), 9.84 (d, J = 1.1 Hz, 1 H, CHO).
13C-NMR (125 MHz, CDCl3): (ppm) = –5.1 (Si(CH3)a), –4.4 (Si(CH3)b), 15.8 (C-4'), 18.3 (SiC), 20.4 (2'-CH3), 21.6 (7'-CH3), 25.8 (SiC(CH3)3), 28.2 (C-3'), 55.4 (5'-OCH3), 77.9 (C-2'), 80.2 (C-2), 103.1, 110.2 (C-6', C-8'), 106.9 (C-4a'), 137.4 (C-7'), 153.3, 157.6 (C-5', C-8a'), 202.4 (CHO).
IR: 𝜈 ̃(cm-1) = 2953, 2929, 2855, 1736, 1619, 1586, 1482, 1415, 1377, 1352, 1252, 1223, 1148, 1107, 885, 835, 813, 777.
UV (CH3CN): max (nm) (lg ) = 207 (4.218), 272 (2.529), 280 (2.504).
MS (ESI): m/z (%) = 387.2 (11) [M+Na]+, 365.2 (6) [M+H]+. C20H32O4Si (364.55) calc.: 387.1962
found: 387.1965 [M+Na]+ (ESI-HRMS).
166 Experimental Section
3.4.7 (2R,2'S)-2-(tert-Butyldimethylsilyloxy)-2-(5-methoxy-2,7-dimethylchroman-2-yl)-acetaldehyde (syn-245)
A solution of alcohol syn-244 (855 mg, 2.33 mmol, 1.00 eq.) in CH2Cl2 (20 mL) was treated with DMP (2.47 g, 5.83 mmol, 2.50 eq.) at 0 °C and the reaction mixture stirred at RT for 2.5 h. The reaction was quenched by addition of sat. aq. NaHCO3 solution (80 mL) at 0 °C.
The aq. layer was extracted with EtOAc (3 × 30 mL) and the combined organic phases were dried over Na2SO4. After evaporation of the organic solvents and column chromatography on silica gel (petroleum ether/EtOAc = 65:1) aldehyde syn-245 was obtained as a colorless oil (755 mg, 2.07 mmol, 89%).
Optical Rotation: []D = –23.6 (c = 0.55, CHCl3, 23.3 °C).
1H-NMR (600 MHz, CDCl3): (ppm) = 0.04 (s, 3 H, Si(CH3)a), 0.06 (s, 3 H, Si(CH3)b), 0.92 (s, 9 H, SiC(CH3)3), 1.76 (ddd, J = 13.7, 10.1, 6.1 Hz, 1 H, 3'-Ha), 1.84 (ddd, J = 13.7, 6.4, 4.4 Hz, 1 H, 3'-Hb), 2.26 (s, 3 H, 7’-CH3), 2.48 (ddd, J = 16.9, 10.1, 6.5 Hz, 1 H, 4'-Ha), 2.71 (ddd, J = 17.3, 6.2, 4.5 Hz, 1 H, 4'-Hb), 3.78 (s, 3 H, 5'-OCH3), 4.04 (s, 1 H, 2-H), 6.23, 6.29 (2 × s, 2 H, 6'-H, 8'-H), 9.72 (s, 1 H, CHO).
13C-NMR (125 MHz, CDCl3): (ppm) = –4.9 (Si(CH3)a), –4.6 (Si(CH3)b), 16.0 (C-4'), 18.4 (SiC), 20.7 (2'-CH3), 21.7 (7'-CH3), 25.8 (SiC(CH3)3), 26.9 (C-3'), 55.4 (5'-OCH3), 77.8 (C-2'), 81.9 (C-2), 103.0, 110.3 (C-6', C-8'), 107.1 (C-4a'), 137.1 (C-7'), 153.1, 157.4 (C-5', C-8a'), 202.4 (C-1).
IR: 𝜈 ̃(cm-1) = 2951, 2929, 2856, 1735, 1619, 1586, 1463, 1352, 1253, 1142, 1108, 1006, 837, 814, 780.
UV (CH3CN): max (nm) (lg ) = 207 (3.948), 272 (2.377), 279 (2.353).
MS (ESI): m/z (%) = 751.4 (5) [2M+Na]+, 387.2 (20) [M+Na]+, 365.2 (25) [M+H]+. C20H32O4Si (364.55) calc.: 365.2143
found: 365.2134, [M+H]+ (ESI-HRMS).
Enantioselective Total Synthesis of (–)-Diversonol 167
3.4.8 Methyl-(2'S,4R)-4-(tert-butyldimethylsilyloxy)-4-(5-methoxy-2,7-dimethylchroman-2-yl)-butanoate (anti-246)
A solution of trimethyl phosphonoacetate (0.71 mL, 4.32 mmol, 1.50 eq.) in THF (22 mL) was treated with sodium hydride (150 mg, 60% (w/w) in mineral oil, 3.75 mmol, 1.30 eq.) at 0 °C. The resulting mixture was stirred at 0 °C for 30 min before a solution of aldehyde anti-245 (1.05 g, 2.88 mmol, 1.00 eq.) in THF (8.5 mL) was added dropwise at 0 °C. After complete addition the mixture was stirred at RT for further 1.5 h before being quenched with sat. aq. NH4Cl solution (50 mL) at 0 °C. The aq. layer was extracted with EtOAc (3 × 20 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. Palladium on charcoal (307 mg, 10% Pd, 288 mol, 10 mol%) was added to a solution of the unsaturated crude product (1.48 g, E/Z = 5:1) in EtOAc (25 mL) in a Parr-flask.
Hydrogen was passed through the resulting mixture for 30 min before being shaken under a H2 atmosphere (4 bar) in a Parr apparatus at RT for further 15 h. The catalyst was removed by filtration through a pad of silica gel (eluting with CH2Cl2). After evaporation of the solvent in vacuo and column chromatography on silica gel (petroleum ether/EtOAc = 30:1 → 5:1), the saturated ester anti-246 was obtained as a colorless oil (1.15 g, 2.72 mmol, 95%).
Optical Rotation: []D = +15.9 (c = 0.50, CHCl3, 27.0 °C).
168 Experimental Section was treated with sodium hydride (108 mg, 60% (w/w) in mineral oil, 2.70 mmol, 1.30 eq.) at 0 °C. The resulting mixture was stirred at 0 °C for 30 min before a solution of aldehyde syn-245 (755 mg, 2.07 mmol, 1.00 eq.) in THF (8.0 mL) was added dropwise at 0 °C. After complete addition the mixture was stirred at RT for further 1.5 h before being quenched with sat. aq. NH4Cl solution (30 mL) at 0 °C. The aq. layers were extracted with EtOAc (3 × 10 mL). The combined organic layer was dried over Na2SO4 and concentrated in vacuo.
Palladium on charcoal (220 mg, 10% Pd, 207 mol, 10 mol%) was added to a solution of the unsaturated crude product in EtOAc (20 mL) in a Parr-flask. Hydrogen was passed through the resulting mixture for 30 min before being shaken under a H2 atmosphere (4 bar) in a Parr apparatus at RT for further 15 h. The catalyst was removed by filtration through a pad of silica gel (eluting with CH2Cl2). After evaporation of the solvent in vacuo and column chromatography on silica gel (petroleum ether/EtOAc = 30:1 → 20:1) the saturated ester syn-246 was obtained as a colorless oil (851 mg, 2.02 mmol, 98%).
Optical Rotation: []D = +0.4 (c = 0.50, CHCl3, 24.1 °C).
Enantioselective Total Synthesis of (–)-Diversonol 169
13C-NMR (125 MHz, CDCl3): (ppm) = –4.5 (Si(CH3)a), –3.6 (Si(CH3)b), 16.1 (C-4'), 17.8 (2'-CH3), 18.6 (SiC), 21.8 (7'-CH3), 26.3 (SiC(CH3)3), 27.6 (C-3), 27.9 (C-3'), 31.2 (C-2), 51.5 (1-OCH3), 55.4 (5'-OCH3), 77.1 (C-4), 79.0 (C-2'), 102.4, 110.2 (C-6', C-8'), 107.1 (C-4a'), 136.9 (C-7'), 153.6, 157.4 (C-5', C-8a'), 174.0 (C-1).
IR: 𝜈 ̃(cm-1) = 2951, 2929, 2855, 1739, 1617, 1585, 1462, 1352, 1248, 1160, 1141, 1102, 1002, 984, 833, 810, 775, 579.
UV (CH3CN): max (nm) (lg ) = 208 (4.238), 273 (2.540), 280 (2.524).
MS (ESI): m/z (%) = 445.3 (100) [M+Na]+, 423.3 (14) [M+H]+. C23H38O5Si (422.63) calc.: 423.2561
found: 423.2551 [M+H]+ (ESI-HRMS).
3.4.10 Methyl-(2'S,4R)-4-(tert-butyldimethylsilyloxy)-4-(5-methoxy-2,7-dimethyl-4-oxochroman-2-yl)-butanoate (anti-247) and Methyl-(2'S,4R)-4-(tert-butyldimethylsilyloxy)-4-(5-methoxy-2,7-dimethyl-2H-chromen-2-yl)-butanoate (anti-248)
Method A: A solution of chromane anti-246 (1.32 g, 3.12 mmol, 1.00 eq.) and tert-butyl hydroperoxide (2.95 mL, 5.5 M in decane, 16.2 mmol, 5.20 eq.) in EtOAc (20 mL) was treated with powdered molecular sieve 3 Å (1.2 g) and the resulting mixture was stirred at RT for 30 min. Thereafter Mn(OAc)3∙2 H2O (86 mg, 312 mol, 10 mol%) was added and the mixture stirred at RT for 4 d. Additional Mn(OAc)3∙2 H2O (86 mg, 312 mol, 10 mol%) and tert-butyl hydroperoxide (0.57 mL, 3.12 mol, 1.00 eq.) were added after 24, 48 and 72 h. The mixture was then filtered through a pad of silica gel (eluting with EtOAc). Evaporation of the solvent in vacuo and column chromatography on silica gel (petroleum ether/EtOAc 30:1 → 1:1) furnished chromanone anti-247 as a yellow oil (701 mg, 1.60 mmol, 51%).
170 Experimental Section
Method B: A mixture of anti-246 (107 mg, 253 mol, 1.00 eq.) and DDQ (115 mg, 507 mol, 2.00 eq.) in benzene (10 mL) was heated at 80 °C for 2 h. After cooling to RT and filtration through a pad of silica gel (eluting with EtOAc) the solvent was removed in vacuo.
Column chromatography of the residue on silica gel (petroleum ether/EtOAc = 30:1 → 10:1) furnished the corresponding chromene anti-248 as a colorless oil (101 mg, 240 mol, 95%).
A solution of the chromene anti-248 (103 mg, 245 mol, 1.00 eq.) in CH2Cl2 (6.1 mL) was refluxed for 4 d (not at night). Additional MnO2 (48 mg, 490 mol, 2.00 eq.) was added every 3 h (4 additions per day, total amount of MnO2: 1.92 g, 19.6 mmol, 80.0 eq.). After filtration through a pad of silica gel (eluting with EtOAc), evaporation of the solvent in vacuo and column chromatography on silica gel (n-hexane/EtOAc = 9:1 → 1:1) the chromanone anti-247 was obtained as a colorless oil (combined yield: 94.7 mg, 217 mol, 88%).
Analytical data of chromene anti-248: 1251, 1223, 1168, 1107, 1005, 991, 834, 814, 773, 713, 667.
UV (CH3CN): max (nm) (lg ) = 230 (4.343), 281 (3.979).
Enantioselective Total Synthesis of (–)-Diversonol 171 powdered molecular sieve 3 Å (83 mg) and the resulting mixture was stirred at RT for 30 min.
172 Experimental Section
Mn(OAc)3∙2 H2O (6.5 mg, 24 µmol, 10 mol%) was added and the resulting reaction mixture was stirred at RT for 4 d; additional Mn(OAc)3∙2 H2O (6.5 mg, 24 µmol, 10 mol%) and tert-butyl hydroperoxide (0.22 mL, 1.23 mmol, 5.20 eq.) were added after 24, 48 and 72 h. The mixture was filtered through a pad of silica gel (eluting with EtOAc). Evaporation of the solvent in vacuo and column chromatography on silica gel (petroleum ether/EtOAc 30:1 → 1:1) furnished chromanone syn-247 as a yellow oil (43 mg, 98.5 µmol, 42%).
Optical Rotation: []D = –42.6 (c = 0.50, CHCl3, 22.6 °C).
1H-NMR (600 MHz, CDCl3): (ppm) = 0.08 (s, 3 H, Si(CH3)a), 0.15 (s, 3 H, Si(CH3)b), 0.90 (s, 9 H, SiC(CH3)3), 1.28 (s, 3 H, 2'-CH3), 1.64 (dtd, J = 14.3, 9.0, 5.5 Hz, 1 H, 3-Ha), 1.88 (mc, 1 H, 3-Hb), 2.28 (s, 3 H, 7'-CH3), 2.39 (ddd, J = 16.2, 9.1, 6.7 Hz, 1 H, 2-Ha), 2.46 (d, J = 15.6 Hz, 1 H, 3'-Ha), 2.54 (ddd, J = 16.4, 9.2, 5.5 Hz, 1 H, 2-Hb), 2.74 (d, J = 15.7 Hz, 1 H, 3'-Hb), 3.65 (s, 3 H, 1-OCH3), 3.82 (dd, J = 8.8, 3.3 Hz, 1 H, 4-H), 3.86 (s, 3 H, 5'-OCH3), 6.26, 6.32 (2 × s, 2 H, 6'-H, 8'-H).
13C-NMR (125 MHz, CDCl3): (ppm) = –4.3 (Si(CH3)a), –3.7 (Si(CH3)b), 17.6 (2'-CH3), 18.5 (SiC), 22.5 (7'-CH3), 26.1 (SiC(CH3)3), 27.6 (C-3), 30.7 (C-2), 46.0 (C-3'), 51.6 (1-OCH3), 56.1 (5'-OCH3), 76.6 (C-4), 83.4 (C-2'), 104.3, 110.5 (C-6', C-8'), 108.4 (C-4a'), 147.4 (C-7'), 160.0 (C-5'), 160.7 (C-8a'), 173.6 (C-1), 190.1 (C-4').
IR: 𝜈 ̃(cm-1) = 2930, 2851, 1739, 1676, 1610, 1569, 1461, 1441, 1418, 1383, 1356, 1303, 1264, 1254, 1215, 1194, 1158, 1118, 1090, 985, 964, 834, 780.
UV (CH3CN): max (nm) (lg ) = 195 (4.407), 222 (4.300), 270 (4.047), 326 (3.632).
Analytical HPLC (Daicel Chiralpak IA®, 4.6 × 250 mm, 5 m, n-hexane/2-PrOH 95:5, 0.8 mL/min): tR = 19.5 min.
MS (ESI): m/z (%) = 895.5 (100) [2M+Na]+, 459.3 (24) [M+Na]+, 437.2 (21) [M+H]+. C23H36O6Si (436.61) calc.: 437.2354
found: 437.2349 [M+H]+ (ESI-HRMS).
Enantioselective Total Synthesis of (–)-Diversonol 173 chromatography on silica gel (n-hexane/EtOAc = 9:1 → 5:1) yielded tetrahydroxanthenone anti-255 as a pale-yellow solid (373 mg, 920 mol, 84%).
Optical Rotation: []D = –78.8 (c = 0.50, CHCl3, 25.1 °C).
174 Experimental Section of Ti(OiPr)Cl3 was transfered slowly through a transfer cannula into the solution of syn-247.
The resulting reaction mixture was stirred at 0 °C for further 2.5 h (TLC monitoring) before being quenched with sat. aq. NaHCO3 solution (25 mL) and H2O (100 mL). The aq. layer was extracted with EtOAc (6 × 50 mL). The combined organic phases were dried over Na2SO4
and the solvent was removed in vacuo. Column chromatography on silica gel (petroleum ether/EtOAc = 10:1 → 5:1) yielded tetrahydroxanthenone syn-255 as a pale-yellow solid (137 mg, 340 mol, 69%).
Enantioselective Total Synthesis of (–)-Diversonol 175 IR: 𝜈 ̃(cm-1) = 2948, 2855, 1605, 1460, 1416, 1378, 1363, 1248, 1225, 1113, 911, 892, 877, 836, 824, 775, 691, 673.
UV (CH3CN): max (nm) (lg ) = 199 (4.528), 283 (3.799), 325 (4.297).
MS (ESI): m/z (%) = 1235.7 (13) [3M+Na]+, 831.5 (88) [2M+Na]+, 427.2 (100) [M+Na]+. C22H32O5Si (404.57) calc.: 427.1911
found: 427.1902 [M+Na]+ (ESI-HRMS).