1: With sulfuric acid; water in acetone T=0 - 5°C; 0.166667 h; 2: With sodium hydrogencarbonate; acetic acid in water; acetone T=0 - 15°C; 0.283333 - 0.416667 h; 3: With sodium acetate in water; acetone T=20°C; pH=5 - 5.5; 60.1667 h; Aqueous sodium acetate buffer;

pyridine hydrogenfluoride in dichloromethane T=25°C;

pyridine hydrogenfluoride in tetrahydrofuran T=50°C;

pyridine; pyridine hydrogenfluoride in tetrahydrofuran Ambient temperature;

1: 31-(trimethylsilylether)rapamycin With 3,5-dimethyl pyridine in dichloromethane T=0 - 5°C; 1.08333 h; Inert atmosphere; 2: dimethylphosphoryl chloride in dichloromethane T=0 - 5°C; 1 h; Inert atmosphere;

1.1: 99 percent / LiBHEt3 / tetrahydrofuran / 0 °C 2.1: tert-butyllithium / tetrahydrofuran / -96 - -78 °C 3.1: 99 percent / 2,6-lutidine / CH2Cl2 / 0.67 h / -78 °C 4.1: 77 percent / tert-butyllithium; hexamethylphosphoramide / tetrahydrofuran / -78 - -40 °C 5.1: 84 percent / (bis(trifluoroacetoxy)iodo)benzene / tetrahydrofuran; H2O; methanol / 20 °C 6.1: 84 percent / 1,3-dicyclohexylcarbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 24 h / -5 °C 7.1: 93 percent / 2,3-dichloro-5,6-dicyano-1,4-benzoquinone / CH2Cl2 / 20 °C / pH 7 8.1: 99 percent / (COCl)2; dimethyl sulfoxide; triethylamine / CH2Cl2 9.1: 82 percent / CrCl2 / tetrahydrofuran / 0 - 20 °C 10.1: N-methylpyrrolidinone; [Pd{P(2-furyl)3}2Cl2]; hexamethyltin / 20 °C 10.2: [Pd{P(2-furyl)3}2Cl2]; N-methylpyrrolidinone / 20 °C 11.1: 81 percent / LiAlH(OtBu)3 / tetrahydrofuran / -10 °C 12.1: 81 percent / 4-pyrrolidinopyridine / CH2Cl2 13.1: 89 percent / lithium hydroxide / H2O; tetrahydrofuran / 0 °C 14.1: 88 percent / 2,6-lutidine / CH2Cl2 / -20 - 20 °C 15.1: 66 percent / 2,6-lutidine / CH2Cl2 / -20 °C 16.1: 88 percent / 1,3-dicyclohexylcarbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 0 - 20 °C 17.1: 81 percent / potassium carbonate / dimethylformamide / 20 °C 18.1: 78 percent / lithium bis(trimethylsilyl)amide / tetrahydrofuran / -78 - -20 °C 19.1: 80 percent / dimedone / [Pd(PPh3)4] / tetrahydrofuran / 20 °C 20.1: PhI(OAc)2 / acetonitrile; H2O / 0 °C 21.1: 2,9-dimethyl-1,10-phenanthroline; pyridine / CH2Cl2 / 20 °C 22.1: 61 percent / pyridine*HF / tetrahydrofuran / 50 °C View Scheme

1.1: tert-butyllithium / tetrahydrofuran / -96 - -78 °C 2.1: 99 percent / 2,6-lutidine / CH2Cl2 / 0.67 h / -78 °C 3.1: 77 percent / tert-butyllithium; hexamethylphosphoramide / tetrahydrofuran / -78 - -40 °C 4.1: 84 percent / (bis(trifluoroacetoxy)iodo)benzene / tetrahydrofuran; H2O; methanol / 20 °C 5.1: 84 percent / 1,3-dicyclohexylcarbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 24 h / -5 °C 6.1: 93 percent / 2,3-dichloro-5,6-dicyano-1,4-benzoquinone / CH2Cl2 / 20 °C / pH 7 7.1: 99 percent / (COCl)2; dimethyl sulfoxide; triethylamine / CH2Cl2 8.1: 82 percent / CrCl2 / tetrahydrofuran / 0 - 20 °C 9.1: N-methylpyrrolidinone; [Pd{P(2-furyl)3}2Cl2]; hexamethyltin / 20 °C 9.2: [Pd{P(2-furyl)3}2Cl2]; N-methylpyrrolidinone / 20 °C 10.1: 81 percent / LiAlH(OtBu)3 / tetrahydrofuran / -10 °C 11.1: 81 percent / 4-pyrrolidinopyridine / CH2Cl2 12.1: 89 percent / lithium hydroxide / H2O; tetrahydrofuran / 0 °C 13.1: 88 percent / 2,6-lutidine / CH2Cl2 / -20 - 20 °C 14.1: 66 percent / 2,6-lutidine / CH2Cl2 / -20 °C 15.1: 88 percent / 1,3-dicyclohexylcarbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 0 - 20 °C 16.1: 81 percent / potassium carbonate / dimethylformamide / 20 °C 17.1: 78 percent / lithium bis(trimethylsilyl)amide / tetrahydrofuran / -78 - -20 °C 18.1: 80 percent / dimedone / [Pd(PPh3)4] / tetrahydrofuran / 20 °C 19.1: PhI(OAc)2 / acetonitrile; H2O / 0 °C 20.1: 2,9-dimethyl-1,10-phenanthroline; pyridine / CH2Cl2 / 20 °C 21.1: 61 percent / pyridine*HF / tetrahydrofuran / 50 °C View Scheme

1.1: 99 percent / diisobutylaluminum hydride / CH2Cl2 / -45 °C 2.1: 70 percent / methanesulfonyl chloride; triethylamine; 4-(dimethylamino)pyridine / lithium bromide / CH2Cl2; dimethylformamide 3.1: 99 percent / LiBHEt3 / tetrahydrofuran / 0 °C 4.1: tert-butyllithium / tetrahydrofuran / -96 - -78 °C 5.1: 99 percent / 2,6-lutidine / CH2Cl2 / 0.67 h / -78 °C 6.1: 77 percent / tert-butyllithium; hexamethylphosphoramide / tetrahydrofuran / -78 - -40 °C 7.1: 84 percent / (bis(trifluoroacetoxy)iodo)benzene / tetrahydrofuran; H2O; methanol / 20 °C 8.1: 84 percent / 1,3-dicyclohexylcarbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 24 h / -5 °C 9.1: 93 percent / 2,3-dichloro-5,6-dicyano-1,4-benzoquinone / CH2Cl2 / 20 °C / pH 7 10.1: 99 percent / (COCl)2; dimethyl sulfoxide; triethylamine / CH2Cl2 11.1: 82 percent / CrCl2 / tetrahydrofuran / 0 - 20 °C 12.1: N-methylpyrrolidinone; [Pd{P(2-furyl)3}2Cl2]; hexamethyltin / 20 °C 12.2: [Pd{P(2-furyl)3}2Cl2]; N-methylpyrrolidinone / 20 °C 13.1: 81 percent / LiAlH(OtBu)3 / tetrahydrofuran / -10 °C 14.1: 81 percent / 4-pyrrolidinopyridine / CH2Cl2 15.1: 89 percent / lithium hydroxide / H2O; tetrahydrofuran / 0 °C 16.1: 88 percent / 2,6-lutidine / CH2Cl2 / -20 - 20 °C 17.1: 66 percent / 2,6-lutidine / CH2Cl2 / -20 °C 18.1: 88 percent / 1,3-dicyclohexylcarbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 0 - 20 °C 19.1: 81 percent / potassium carbonate / dimethylformamide / 20 °C 20.1: 78 percent / lithium bis(trimethylsilyl)amide / tetrahydrofuran / -78 - -20 °C 21.1: 80 percent / dimedone / [Pd(PPh3)4] / tetrahydrofuran / 20 °C 22.1: PhI(OAc)2 / acetonitrile; H2O / 0 °C 23.1: 2,9-dimethyl-1,10-phenanthroline; pyridine / CH2Cl2 / 20 °C 24.1: 61 percent / pyridine*HF / tetrahydrofuran / 50 °C View Scheme

1.1: 70 percent / methanesulfonyl chloride; triethylamine; 4-(dimethylamino)pyridine / lithium bromide / CH2Cl2; dimethylformamide 2.1: 99 percent / LiBHEt3 / tetrahydrofuran / 0 °C 3.1: tert-butyllithium / tetrahydrofuran / -96 - -78 °C 4.1: 99 percent / 2,6-lutidine / CH2Cl2 / 0.67 h / -78 °C 5.1: 77 percent / tert-butyllithium; hexamethylphosphoramide / tetrahydrofuran / -78 - -40 °C 6.1: 84 percent / (bis(trifluoroacetoxy)iodo)benzene / tetrahydrofuran; H2O; methanol / 20 °C 7.1: 84 percent / 1,3-dicyclohexylcarbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 24 h / -5 °C 8.1: 93 percent / 2,3-dichloro-5,6-dicyano-1,4-benzoquinone / CH2Cl2 / 20 °C / pH 7 9.1: 99 percent / (COCl)2; dimethyl sulfoxide; triethylamine / CH2Cl2 10.1: 82 percent / CrCl2 / tetrahydrofuran / 0 - 20 °C 11.1: N-methylpyrrolidinone; [Pd{P(2-furyl)3}2Cl2]; hexamethyltin / 20 °C 11.2: [Pd{P(2-furyl)3}2Cl2]; N-methylpyrrolidinone / 20 °C 12.1: 81 percent / LiAlH(OtBu)3 / tetrahydrofuran / -10 °C 13.1: 81 percent / 4-pyrrolidinopyridine / CH2Cl2 14.1: 89 percent / lithium hydroxide / H2O; tetrahydrofuran / 0 °C 15.1: 88 percent / 2,6-lutidine / CH2Cl2 / -20 - 20 °C 16.1: 66 percent / 2,6-lutidine / CH2Cl2 / -20 °C 17.1: 88 percent / 1,3-dicyclohexylcarbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 0 - 20 °C 18.1: 81 percent / potassium carbonate / dimethylformamide / 20 °C 19.1: 78 percent / lithium bis(trimethylsilyl)amide / tetrahydrofuran / -78 - -20 °C 20.1: 80 percent / dimedone / [Pd(PPh3)4] / tetrahydrofuran / 20 °C 21.1: PhI(OAc)2 / acetonitrile; H2O / 0 °C 22.1: 2,9-dimethyl-1,10-phenanthroline; pyridine / CH2Cl2 / 20 °C 23.1: 61 percent / pyridine*HF / tetrahydrofuran / 50 °C View Scheme

1.1: 75 percent / lipase PS-30 / 1,2-dimethoxy-ethane / 14 h / 20 °C 2.1: 99 percent / SO3*pyridine; ethyldiisopropylamine / CH2Cl2; dimethylsulfoxide / 0 °C 3.1: sBuLi; (-)-(MeO)B(isopinocampheyl)2; BF3*OEt2 / tetrahydrofuran / 14 h / -78 °C 3.2: NaOH; H2O2 / H2O / -78 - 20 °C 4.1: sodium carbonate / methanol / 20 °C 5.1: 99 percent / sodium hydride; tetrabutylammonium iodide / dimethylformamide / 20 °C 6.1: N-methylmorpholine N-oxide; OsO4 / acetone; H2O / 20 °C 6.2: Pb(OAc)4 / benzene 7.1: tert-butyllithium / tetrahydrofuran / -96 - -78 °C 8.1: 99 percent / 2,6-lutidine / CH2Cl2 / 0.67 h / -78 °C 9.1: 77 percent / tert-butyllithium; hexamethylphosphoramide / tetrahydrofuran / -78 - -40 °C 10.1: 84 percent / (bis(trifluoroacetoxy)iodo)benzene / tetrahydrofuran; H2O; methanol / 20 °C 11.1: 84 percent / 1,3-dicyclohexylcarbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 24 h / -5 °C 12.1: 93 percent / 2,3-dichloro-5,6-dicyano-1,4-benzoquinone / CH2Cl2 / 20 °C / pH 7 13.1: 99 percent / (COCl)2; dimethyl sulfoxide; triethylamine / CH2Cl2 14.1: 82 percent / CrCl2 / tetrahydrofuran / 0 - 20 °C 15.1: N-methylpyrrolidinone; [Pd{P(2-furyl)3}2Cl2]; hexamethyltin / 20 °C 15.2: [Pd{P(2-furyl)3}2Cl2]; N-methylpyrrolidinone / 20 °C 16.1: 81 percent / LiAlH(OtBu)3 / tetrahydrofuran / -10 °C 17.1: 81 percent / 4-pyrrolidinopyridine / CH2Cl2 18.1: 89 percent / lithium hydroxide / H2O; tetrahydrofuran / 0 °C 19.1: 88 percent / 2,6-lutidine / CH2Cl2 / -20 - 20 °C 20.1: 66 percent / 2,6-lutidine / CH2Cl2 / -20 °C 21.1: 88 percent / 1,3-dicyclohexylcarbodiimide; 4-(dimethylamino)pyridine / CH2Cl2 / 0 - 20 °C 22.1: 81 percent / potassium carbonate / dimethylformamide / 20 °C 23.1: 78 percent / lithium bis(trimethylsilyl)amide / tetrahydrofuran / -78 - -20 °C 24.1: 80 percent / dimedone / [Pd(PPh3)4] / tetrahydrofuran / 20 °C 25.1: PhI(OAc)2 / acetonitrile; H2O / 0 °C 26.1: 2,9-dimethyl-1,10-phenanthroline; pyridine / CH2Cl2 / 20 °C 27.1: 61 percent / pyridine*HF / tetrahydrofuran / 50 °C View Scheme