氨基羰基羧基羟基保护基团及其稳定性
Amino Protecting Groups Stability
Protecting group is stable under these conditions Protecting group is moderately stable / might react Protecting group is labile
9-Fluorenylmethyl carbamate, FMOC amino, FMOC amine, FMOC
Fmoc-NR 2
amide
H 2O: Bases:
pH
pH = 1, RTpH = 4, RTpH = 9, RTNEt 3, Py RMgX RCHO H 2 / Rh OsO 4
t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
Others: Enolates Others: Na / NH3
pH = 12, RT DCC NH 3, RNH 2:CCl2LiAlH 4
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
Nucleophiles:RLi Electrophiles:RCOCl Reduction: Oxidation:
H 2 / Ni KMnO 4
RCOOOH I 2, Br2, Cl2MnO 2/CH2Cl 2
t -Butyl carbamate, BOC amine, BOC amino, BOC amide
H 2O: Bases: Nucleophiles:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO
4
Cbz-NR 2 / Z-NR2Benzyl carbamate
H 2O: Bases:
pH
100°C LDA
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4MnO 2 / CH 2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl Reduction:
Oxidation:
H 2 / Ni KMnO 4
Ac-NR 2Acetamide
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO 4
Trifluoroacetamide
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2O: Bases:
H 2 / Ni KMnO 4
Phthalimide
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO 4
Bn-NR 2Benzylamine
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO 4
Tr-NR 2Triphenylmethylamine (Tritylamine)
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°CSOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO 4
Benzylideneamine
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO
4
Ts-NR 2p -Toluenesulfonamide, Tosylamide
H 2O: Bases: Nucleophiles:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT pH > 12, 100°CDCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO 4
Carbonyl Protecting Groups Stability
Dimethyl acetal
H 2O: Bases:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO
4
H 2O: Bases:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO
4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi
Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO
4
H 2O: Bases:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT pH > 12, 100°C DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi
Electrophiles: RCOCl
H 2 / Ni Reduction: Oxidation:
KMnO 4
N,N -Dimethylhydrazone
H 2O: Bases: Nucleophiles:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Electrophiles: Reduction: Oxidation:
Methyl ester
H 2O: Bases:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi
Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO 4
t -Butyl ester
H 2O: Bases:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi
Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO 4
Benzyl ester
H 2O: Bases:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT pH > 12, 100°C DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO 4
S-t-Butyl ester
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°CSOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO 4
2-Alkyl-1,3-oxazoline
H 2O: Bases: Nucleophiles:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Electrophiles: Reduction: Oxidation:
MOM-OR
Methoxymethyl ether, MOM ether
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi
Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO 4
Tetrahydropyranyl ether, THP ether
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO 4
t -Butyl ether
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO 4
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi
Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO
4
Bn-OR Benzyl ether
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi
Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO 4
t -Butyldimethylsilyl ether, TBDMS ether
H 2O: Bases: Nucleophiles:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO 4
TBDPS-OR t -Butyldiphenylsilyl ether, TBDPS ether
H 2O: Bases:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT pH > 12, 100°C DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl Reduction:
Oxidation:
H 2 / Ni KMnO 4
Ac-OR Acetic acid ester, Acetate ester, Acetate
H 2O: Bases: Nucleophiles:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Electrophiles: RCOCl Reduction: Oxidation:
H 2 / Ni KMnO 4
Pv-OR Pivalic acid ester, Pivalate ester, Pivalate
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°CSOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO 4
Bz-OR Benzoic acid ester, Benzoate ester, Benzoate
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO 4
1,2- and 1,3-diols
Acetonide
H 2O: Bases:
pH
NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°CSOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO 4
Benzylidene acetal
H 2O: Bases:
pH
pH = 1, RT NEt 3, Py RMgX RCHO H 2 / Rh OsO 4
pH = 4, RT t-BuOK RCuLi CH 3I Zn / HCl CrO 3 / Py
pH = 9, RT Others: Enolates Others: Na / NH3RCOOOH
pH = 12, RT DCC NH 3, RNH2:CCl2LiAlH 4I 2, Br2, Cl2
pH > 12, 100°C SOCl 2NaOCH 3Bu 3SnH NaBH 4
MnO 2 / CH2Cl 2
Nucleophiles: RLi Electrophiles: RCOCl
Reduction: Oxidation:
H 2 / Ni KMnO 4
T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, New York, 1999, 207-215, 716-719.