氨基羰基羧基羟基保护基团及其稳定性

http://www.organic-chemistry.org/ Amino Protecting Groups Stability Protecting group is stable under these conditions Protecting group is moderately stable / might react Protecting group is labile Fmoc-NR2 9-Fluorenylmethyl carbamate, FMOC amino, FMOC amine, FMOC amide H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2/CH2Cl2 BOC-NR 2 t-Butyl carbamate, BOC amine, BOC amino, BOC amide H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Cbz-NR2 / Z-NR2 Benzyl carbamate H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Ac-NR2 Acetamide H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 http://www.organic-chemistry.org/ Trifluoroacetamide H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Phthalimide H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Bn-NR2 Benzylamine H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Tr-NR2 Triphenylmethylamine (Tritylamine) H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Benzylideneamine H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Ts-NR2 p-Toluenesulfonamide, Tosylamide H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 http://www.organic-chemistry.org/ Carbonyl Protecting Groups Stability Dimethyl acetal H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 1,3- Dioxanes 1,3-Dioxolanes H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 1,3-Dithianes 1,3-Dithiolanes H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 N,N- Dimethylhydrazone H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 http://www.organic-chemistry.org/ Carboxyl Protecting Groups Stability Methyl ester H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 t-Butyl ester H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Benzyl ester H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 S-t-Butyl ester H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 2-Alkyl-1,3-oxazoline H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 http://www.organic-chemistry.org/ Hydroxyl Protecting Groups Stability MOM-OR Methoxymethyl ether, MOM ether H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 THP-OR Tetrahydropyranyl ether, THP ether H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 t-Butyl ether H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Allyl ether H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Bn-OR Benzyl ether H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 http://www.organic-chemistry.org/ TBDMS-OR t-Butyldimethylsilyl ether, TBDMS ether H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 TBDPS-OR t-Butyldiphenylsilyl ether, TBDPS ether H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Ac-OR Acetic acid ester, Acetate ester, Acetate H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Pv-OR Pivalic acid ester, Pivalate ester, Pivalate H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Bz-OR Benzoic acid ester, Benzoate ester, Benzoate H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 http://www.organic-chemistry.org/ 1,2- and 1,3-diols Acetonide H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Benzylidene acetal H2O: pH < 1, 100°C pH = 1, RT pH = 4, RT pH = 9, RT pH = 12, RT pH > 12, 100°C Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, New York, 1999, 207-215, 716-719. Amino Protecting Groups Stability Carbonyl Protecting Groups Stability Carboxyl Protecting Groups Stability Hydroxyl Protecting Groups Stability 1,2- and 1,3-diols