1: 1) Sn(OTf)2, N-ethylpiperidine / 1) THF, -78 deg C, 90 min, 2) 2 h 2: 90 percent / MeMgBr / diethyl ether; CH2Cl2 / 0.05 h / 0 °C 3: 90 percent / DMAP / CH2Cl2 / 0.17 h 4: 30percent H2O2, HCO2H / CH2Cl2 / 0.5 h / 0 °C 5: 2) 2M Na2CO3 / 1) Pd(PPh3)4 / 1) THF, 1 h, reflux, 2) 24 h, reflux 6: 80 percent / Cs2CO3 / methanol / 2 h / Ambient temperature 7: 95 percent / tetramethylguanidine / tetrahydrofuran / 1) -70 to -30 deg C, 5 h, 2) -30 deg C, 2 d, 3) RT, 15 h 8: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 9: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 10: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 11: 71 percent / HOAc / H2O / 4 h / 50 °C 12: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 13: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 14: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 15: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 16: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 17: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme

2: 90 percent / LiOH*H2O / dioxane; H2O / 1) RT, 5 h, ultrasound, 2) 50 deg C, 15 h 3: 1-chloro-1-(N,N-dimethylamino)-2-methyl-1-propene / CH2Cl2 / 0.25 h / 0 °C 4: 1) n-BuLi / 1) THF, hexane, -70 deg C, 20 min, 2a) -70 deg C to RT, 2b) RT, 15 h 5: H2 / <(R)-(RuCl(p-cymene)BINAP>Cl / methanol; CH2Cl2 / 72 h / 50 °C / 37503 Torr 6: 97 percent / aq. HOAc / 3 h / 50 °C 7: 95 percent / tetramethylguanidine / tetrahydrofuran / 1) -70 to -30 deg C, 5 h, 2) -30 deg C, 2 d, 3) RT, 15 h 8: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 9: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 10: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 11: 71 percent / HOAc / H2O / 4 h / 50 °C 12: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 13: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 14: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 15: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 16: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 17: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme

1: 90 percent / DMAP / CH2Cl2 / 0.17 h 2: 30percent H2O2, HCO2H / CH2Cl2 / 0.5 h / 0 °C 3: 2) 2M Na2CO3 / 1) Pd(PPh3)4 / 1) THF, 1 h, reflux, 2) 24 h, reflux 4: 80 percent / Cs2CO3 / methanol / 2 h / Ambient temperature 5: 95 percent / tetramethylguanidine / tetrahydrofuran / 1) -70 to -30 deg C, 5 h, 2) -30 deg C, 2 d, 3) RT, 15 h 6: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 7: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 8: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 9: 71 percent / HOAc / H2O / 4 h / 50 °C 10: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 11: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 12: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 13: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 14: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 15: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme

1: 2) 2M Na2CO3 / 1) Pd(PPh3)4 / 1) THF, 1 h, reflux, 2) 24 h, reflux 2: 80 percent / Cs2CO3 / methanol / 2 h / Ambient temperature 3: 95 percent / tetramethylguanidine / tetrahydrofuran / 1) -70 to -30 deg C, 5 h, 2) -30 deg C, 2 d, 3) RT, 15 h 4: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 5: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 6: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 7: 71 percent / HOAc / H2O / 4 h / 50 °C 8: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 9: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 10: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 11: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 12: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 13: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme

1: 30percent H2O2, HCO2H / CH2Cl2 / 0.5 h / 0 °C 2: 2) 2M Na2CO3 / 1) Pd(PPh3)4 / 1) THF, 1 h, reflux, 2) 24 h, reflux 3: 80 percent / Cs2CO3 / methanol / 2 h / Ambient temperature 4: 95 percent / tetramethylguanidine / tetrahydrofuran / 1) -70 to -30 deg C, 5 h, 2) -30 deg C, 2 d, 3) RT, 15 h 5: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 6: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 7: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 8: 71 percent / HOAc / H2O / 4 h / 50 °C 9: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 10: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 11: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 12: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 13: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 14: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme

1: 95 percent / tetramethylguanidine / tetrahydrofuran / 1) -70 to -30 deg C, 5 h, 2) -30 deg C, 2 d, 3) RT, 15 h 2: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 3: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 4: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 5: 71 percent / HOAc / H2O / 4 h / 50 °C 6: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 7: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 8: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 9: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 10: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 11: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme

1: 80 percent / Cs2CO3 / methanol / 2 h / Ambient temperature 2: 95 percent / tetramethylguanidine / tetrahydrofuran / 1) -70 to -30 deg C, 5 h, 2) -30 deg C, 2 d, 3) RT, 15 h 3: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 4: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 5: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 6: 71 percent / HOAc / H2O / 4 h / 50 °C 7: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 8: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 9: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 10: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 11: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 12: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme

1: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 2: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 3: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 4: 71 percent / HOAc / H2O / 4 h / 50 °C 5: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 6: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 7: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 8: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 9: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 10: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme

1: 98 percent / methanol; diethyl ether 3: 90 percent / LiOH*H2O / dioxane; H2O / 1) RT, 5 h, ultrasound, 2) 50 deg C, 15 h 4: 1-chloro-1-(N,N-dimethylamino)-2-methyl-1-propene / CH2Cl2 / 0.25 h / 0 °C 5: 1) n-BuLi / 1) THF, hexane, -70 deg C, 20 min, 2a) -70 deg C to RT, 2b) RT, 15 h 6: H2 / <(R)-(RuCl(p-cymene)BINAP>Cl / methanol; CH2Cl2 / 72 h / 50 °C / 37503 Torr 7: 97 percent / aq. HOAc / 3 h / 50 °C 8: 95 percent / tetramethylguanidine / tetrahydrofuran / 1) -70 to -30 deg C, 5 h, 2) -30 deg C, 2 d, 3) RT, 15 h 9: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 10: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 11: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 12: 71 percent / HOAc / H2O / 4 h / 50 °C 13: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 14: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 15: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 16: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 17: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 18: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme

2: 90 percent / LiOH*H2O / dioxane; H2O / 1) RT, 5 h, ultrasound, 2) 50 deg C, 15 h 3: 1-chloro-1-(N,N-dimethylamino)-2-methyl-1-propene / CH2Cl2 / 0.25 h / 0 °C 4: 1) n-BuLi / 1) THF, hexane, -70 deg C, 20 min, 2a) -70 deg C to RT, 2b) RT, 15 h 5: H2 / <(R)-(RuCl(p-cymene)BINAP>Cl / methanol; CH2Cl2 / 72 h / 50 °C / 37503 Torr 6: 97 percent / aq. HOAc / 3 h / 50 °C 7: 95 percent / tetramethylguanidine / tetrahydrofuran / 1) -70 to -30 deg C, 5 h, 2) -30 deg C, 2 d, 3) RT, 15 h 8: 85 percent / H2 / (R,R)-<Rh(1,5-COD)(DIPAMP)>BF4 / methanol; CH2Cl2 / 48 h / 2250.2 Torr / Ambient temperature 9: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 10: hydroxybenzotriazole, N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide*HCl / CH2Cl2 / 15 h / -10 deg C to RT 11: 71 percent / HOAc / H2O / 4 h / 50 °C 12: 96 percent / Bu4NF*3H2O / dimethylformamide / 2 h / Ambient temperature 13: EDCI / CH2Cl2 / 15 h / -10 deg C to RT 14: 6M HCl / dioxane; CH2Cl2 / 0.5 h / Ambient temperature 15: aq. KHCO3 / CHCl3 / 1) RT, 2 h, 2) 50 deg C, 30 min 16: 95 percent / 1M LiOH / H2O; dioxane / 2 h / 10 °C 17: thioanisole, BrSiMe3, CF3COOH / 1 h / 0 °C View Scheme