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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: Bases: pH < 1, 100C LDA pH = 1, RT pH = 4, RT pH = 9, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

I2, Br2, Cl2 MnO2/CH2Cl2

BOC-NR2

t-Butyl carbamate, BOC amine, BOC amino, BOC amide

H2O: Bases: Nucleophiles: Electrophiles: Reduction: Oxidation: pH < 1, 100C pH = 1, RT LDA RLi RCOCl H2 / Ni KMnO4 NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Cbz-NR2 / Z-NR2

Benzyl carbamate
H2O: Bases: pH < 1, 100C LDA pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Ac-NR2

Acetamide
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

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Trifluoroacetamide
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Phthalimide
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Bn-NR2

Benzylamine
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Tr-NR2

Triphenylmethylamine (Tritylamine)
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Benzylideneamine
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Ts-NR2

p-Toluenesulfonamide, Tosylamide
H2O: Bases: Nucleophiles: Electrophiles: Reduction: Oxidation: pH < 1, 100C LDA RLi RCOCl H2 / Ni KMnO4 pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT pH > 12, 100C DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

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Carbonyl Protecting Groups Stability

Dimethyl acetal
H2O: Bases: pH < 1, 100C LDA pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

1,3Dioxanes

1,3-Dioxolanes
H2O: Bases: pH < 1, 100C LDA pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

1,3-Dithianes

1,3Dithiolanes
H2O: Bases: pH < 1, 100C LDA pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

N,NDimethylhydrazone
H2O: Bases: Nucleophiles: Electrophiles: Reduction: Oxidation: pH < 1, 100C LDA RLi RCOCl H2 / Ni KMnO4 pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

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Carboxyl Protecting Groups Stability

Methyl ester
H2O: Bases: pH < 1, 100C LDA pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

t-Butyl ester
H2O: Bases: pH < 1, 100C LDA pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Benzyl ester
H2O: Bases: pH < 1, 100C LDA pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

S-t-Butyl ester
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

2-Alkyl-1,3-oxazoline
H2O: Bases: Nucleophiles: Electrophiles: Reduction: Oxidation: pH < 1, 100C LDA RLi RCOCl H2 / Ni KMnO4 pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

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Hydroxyl Protecting Groups Stability

MOM-OR Methoxymethyl ether, MOM ether
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

THP-OR

Tetrahydropyranyl ether, THP ether

H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

t-Butyl ether
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Allyl ether
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Bn-OR

Benzyl ether
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

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TBDMS-OR t-Butyldimethylsilyl ether, TBDMS ether
H2O: Bases: Nucleophiles: Electrophiles: Reduction: Oxidation: pH < 1, 100C LDA RLi RCOCl H2 / Ni KMnO4 pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

TBDPS-OR

t-Butyldiphenylsilyl ether, TBDPS ether

H2O: Bases: pH < 1, 100C LDA pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT pH > 12, 100C DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Ac-OR

Acetic acid ester, Acetate ester, Acetate

H2O: Bases: Nucleophiles: Electrophiles: Reduction: Oxidation: pH < 1, 100C LDA RLi RCOCl H2 / Ni KMnO4 pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Pv-OR

Pivalic acid ester, Pivalate ester, Pivalate

H2O: Bases: Nucleophiles: pH < 1, 100C pH = 1, RT LDA RLi NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Bz-OR

Benzoic acid ester, Benzoate ester, Benzoate

H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

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1,2- and 1,3-diols

Acetonide
H2O: Bases: pH < 1, 100C pH = 1, RT LDA NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

Benzylidene acetal
H2O: Bases: pH < 1, 100C LDA pH = 1, RT NEt3, Py RMgX RCHO H2 / Rh OsO4 pH = 4, RT t-BuOK RCuLi CH3I Zn / HCl CrO3 / Py pH = 9, RT Others: Enolates Others: Na / NH3 RCOOOH pH = 12, RT DCC NH3, RNH2 :CCl2 LiAlH4 I2, Br2, Cl2 pH > 12, 100C SOCl2 NaOCH3 Bu3SnH NaBH4 MnO2 / CH2Cl2

Nucleophiles: RLi Electrophiles: RCOCl Reduction: Oxidation: H2 / Ni KMnO4

T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, New York, 1999, 207-215, 716-719.