methoxybenzene; trifluoroacetic acid in dichloromethane T=-20 - -10°C; Substitution; 0.416667 h;

hydrogen fluoride in tetrahydrofuran 18 h; Ambient temperature;

1: LiEt3BH / tetrahydrofuran / 1.17 h / Heating 2: (COCl)2, DMSO 3: potassium tert-butoxide / tetrahydrofuran / -78 deg C -> r.t. 4: 1.) Cp2ZrCl2, 2.) I2 / 1.) dichloroethane, 23,5 h, 2.)THF, -25 deg C to -10 deg C, 140 min 5: 84 percent / Ag2CO3, triethylamine / Pd(OAc)2 / CH2Cl2; ethanol / 1.25 h 6: 1.) 2,2,6,6-tetramethyl-1-oxopiperidinium chloride, 2.) NaClO2, NaH2PO4*H2O / 1.) CH2Cl2, -20 deg C, 10 min, then -15 deg C, 2 h, 2.) 2-methylbutene, H2O 7: 70 percent / benzenesulfonyl chloride, pyridine / 18.5 h / 0 - 10 °C 8: 78 percent / aq. HF / tetrahydrofuran / 8.5 h View Scheme

2: 1.) O3, 2.) NaBH4 / 1.) CH2Cl2, MeOH, -78 deg C, 2.) -> r.t., overnight 3: pyridine, 4-(N,N-dimethylamino)pyridine / 2 h / 0 °C 4: diisopropylethylamine / CH2Cl2 / 0.5 h / 0 °C 5: LiEt3BH / tetrahydrofuran / 1.17 h / Heating 6: (COCl)2, DMSO 7: potassium tert-butoxide / tetrahydrofuran / -78 deg C -> r.t. 8: 1.) Cp2ZrCl2, 2.) I2 / 1.) dichloroethane, 23,5 h, 2.)THF, -25 deg C to -10 deg C, 140 min 9: 84 percent / Ag2CO3, triethylamine / Pd(OAc)2 / CH2Cl2; ethanol / 1.25 h 10: 1.) 2,2,6,6-tetramethyl-1-oxopiperidinium chloride, 2.) NaClO2, NaH2PO4*H2O / 1.) CH2Cl2, -20 deg C, 10 min, then -15 deg C, 2 h, 2.) 2-methylbutene, H2O 11: 70 percent / benzenesulfonyl chloride, pyridine / 18.5 h / 0 - 10 °C 12: 78 percent / aq. HF / tetrahydrofuran / 8.5 h View Scheme

1: 77 percent / Ph3P, pyridine, diethyl azodicarboxylate / tetrahydrofuran / 5 h / -45 deg C to 0 deg C 2: 91 percent / K2CO3 / methanol / 2.5 h 4: 1.) O3, 2.) NaBH4 / 1.) CH2Cl2, MeOH, -78 deg C, 2.) -> r.t., overnight 5: pyridine, 4-(N,N-dimethylamino)pyridine / 2 h / 0 °C 6: diisopropylethylamine / CH2Cl2 / 0.5 h / 0 °C 7: LiEt3BH / tetrahydrofuran / 1.17 h / Heating 8: (COCl)2, DMSO 9: potassium tert-butoxide / tetrahydrofuran / -78 deg C -> r.t. 10: 1.) Cp2ZrCl2, 2.) I2 / 1.) dichloroethane, 23,5 h, 2.)THF, -25 deg C to -10 deg C, 140 min 11: 84 percent / Ag2CO3, triethylamine / Pd(OAc)2 / CH2Cl2; ethanol / 1.25 h 12: 1.) 2,2,6,6-tetramethyl-1-oxopiperidinium chloride, 2.) NaClO2, NaH2PO4*H2O / 1.) CH2Cl2, -20 deg C, 10 min, then -15 deg C, 2 h, 2.) 2-methylbutene, H2O 13: 70 percent / benzenesulfonyl chloride, pyridine / 18.5 h / 0 - 10 °C 14: 78 percent / aq. HF / tetrahydrofuran / 8.5 h View Scheme

1: 1.) O3, 2.) NaBH4 / 1.) CH2Cl2, MeOH, -78 deg C, 2.) -> r.t., overnight 2: pyridine, 4-(N,N-dimethylamino)pyridine / 2 h / 0 °C 3: diisopropylethylamine / CH2Cl2 / 0.5 h / 0 °C 4: LiEt3BH / tetrahydrofuran / 1.17 h / Heating 5: (COCl)2, DMSO 6: potassium tert-butoxide / tetrahydrofuran / -78 deg C -> r.t. 7: 1.) Cp2ZrCl2, 2.) I2 / 1.) dichloroethane, 23,5 h, 2.)THF, -25 deg C to -10 deg C, 140 min 8: 84 percent / Ag2CO3, triethylamine / Pd(OAc)2 / CH2Cl2; ethanol / 1.25 h 9: 1.) 2,2,6,6-tetramethyl-1-oxopiperidinium chloride, 2.) NaClO2, NaH2PO4*H2O / 1.) CH2Cl2, -20 deg C, 10 min, then -15 deg C, 2 h, 2.) 2-methylbutene, H2O 10: 70 percent / benzenesulfonyl chloride, pyridine / 18.5 h / 0 - 10 °C 11: 78 percent / aq. HF / tetrahydrofuran / 8.5 h View Scheme

1: 84 percent / Ag2CO3, triethylamine / Pd(OAc)2 / CH2Cl2; ethanol / 1.25 h 2: 1.) 2,2,6,6-tetramethyl-1-oxopiperidinium chloride, 2.) NaClO2, NaH2PO4*H2O / 1.) CH2Cl2, -20 deg C, 10 min, then -15 deg C, 2 h, 2.) 2-methylbutene, H2O 3: 70 percent / benzenesulfonyl chloride, pyridine / 18.5 h / 0 - 10 °C 4: 78 percent / aq. HF / tetrahydrofuran / 8.5 h View Scheme

1: 86 percent / Me2AlCl / CH2Cl2; hexane / 2 h / -20 - -15 °C 2: 84 percent / Ag2CO3, triethylamine / Pd(OAc)2 / CH2Cl2; ethanol / 1.25 h 3: 1.) 2,2,6,6-tetramethyl-1-oxopiperidinium chloride, 2.) NaClO2, NaH2PO4*H2O / 1.) CH2Cl2, -20 deg C, 10 min, then -15 deg C, 2 h, 2.) 2-methylbutene, H2O 4: 70 percent / benzenesulfonyl chloride, pyridine / 18.5 h / 0 - 10 °C 5: 78 percent / aq. HF / tetrahydrofuran / 8.5 h View Scheme

1: 93 percent / CrO3-pyridine / CH2Cl2 / 15 h / Ambient temperature 2: 38 percent / p-toluenesulfonic acid monohydrate / benzene / 4 h / Heating 3: 1.) ozone, 2.) dimethyl sulfide / 1a.) CH2Cl2, -78 deg C, 1 h, 1b.) RT, 0.5 h, 2.) RT, 1 h 4: 1.) sodium hydride / 1.) THF, 15 min, 2.) RT, 4 h 5: 98 percent / H2 / 10percent Pd/C / ethyl acetate / 0.5 h / 2068.6 Torr / Ambient temperature 6: 90 percent / DIBAH / toluene / 0.5 h / -78 °C 9: 79 percent / N,N-diisopropylethylamine / CH2Cl2 / 19 h / Ambient temperature 10: 1.) ozone, 2.) Me2S / 1a.) CH2Cl2, -78 deg C, 0.5 h, 1b.) RT, O.5 h, 2.) RT, 1 h 11: pyridinium dichromate / dimethylformamide / 17 h / Ambient temperature 12: dimethylformamide; H2O; diethyl ether / 1 h / Ambient temperature 13: 72 percent / ZnBr2 / CH2Cl2 / 3 h / Ambient temperature 14: 96 percent / aq. NaOH / propan-2-ol / 0.5 h / 60 °C 15: 48 percent / benzenesulfonyl chloride, pyridine 16: 44 percent / Zn, dibromoethane / tetrahydrofuran / 1.12 h / Heating 17: 30 percent / SOCl2, pyridine / CH2Cl2 / 0.08 h / Heating 18: 76 percent / 50percent aq. HF / tetrahydrofuran / 18 h / Ambient temperature View Scheme

1: 84 percent 2: 93 percent / CrO3-pyridine / CH2Cl2 / 15 h / Ambient temperature 3: 38 percent / p-toluenesulfonic acid monohydrate / benzene / 4 h / Heating 4: 1.) ozone, 2.) dimethyl sulfide / 1a.) CH2Cl2, -78 deg C, 1 h, 1b.) RT, 0.5 h, 2.) RT, 1 h 5: 1.) sodium hydride / 1.) THF, 15 min, 2.) RT, 4 h 6: 98 percent / H2 / 10percent Pd/C / ethyl acetate / 0.5 h / 2068.6 Torr / Ambient temperature 7: 90 percent / DIBAH / toluene / 0.5 h / -78 °C 10: 79 percent / N,N-diisopropylethylamine / CH2Cl2 / 19 h / Ambient temperature 11: 1.) ozone, 2.) Me2S / 1a.) CH2Cl2, -78 deg C, 0.5 h, 1b.) RT, O.5 h, 2.) RT, 1 h 12: pyridinium dichromate / dimethylformamide / 17 h / Ambient temperature 13: dimethylformamide; H2O; diethyl ether / 1 h / Ambient temperature 14: 72 percent / ZnBr2 / CH2Cl2 / 3 h / Ambient temperature 15: 96 percent / aq. NaOH / propan-2-ol / 0.5 h / 60 °C 16: 48 percent / benzenesulfonyl chloride, pyridine 17: 44 percent / Zn, dibromoethane / tetrahydrofuran / 1.12 h / Heating 18: 30 percent / SOCl2, pyridine / CH2Cl2 / 0.08 h / Heating 19: 76 percent / 50percent aq. HF / tetrahydrofuran / 18 h / Ambient temperature View Scheme