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PROTECTIVE GROUPS IN ORGANIC SYNTHESIS

PROTECTIVE GROUPS IN ORGANIC SYNTHESIS. MOM-OR. Methoxymethyl ether, MOM ether. H 2 O:. pH < 1, 100°C. pH = 1, RT. pH = 4, RT. pH = 9, RT. pH = 12, RT. pH > 12, 100°C. Bases:. LDA. NEt 3 , Py. t-BuOK. Others:. DCC. SOCl 2. Nucleophiles:. RLi. RMgX. RCuLi. Enolates.

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PROTECTIVE GROUPS IN ORGANIC SYNTHESIS

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  1. PROTECTIVE GROUPS IN ORGANIC SYNTHESIS

  2. 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 Hydroxyl Protecting Groups Stability T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, New York, 1999, 49-54, 708-711.

  3. 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 Hydroxyl Protecting Groups Stability T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, New York, 1999, 49-54, 708-711.

  4. Bn-OR Benzyl ether 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 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 Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 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 Hydroxyl Protecting Groups Stability T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, New York, 1999, 49-54, 708-711.

  5. 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, Pivlate 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 Hydroxyl Protecting Groups Stability T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, New York, 1999, 49-54, 708-711.

  6. 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 Hydroxyl Protecting Groups Stability 1,2- and 1,3-diols T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley-Interscience, New York, 1999, 49-54, 708-711.

  7. 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 Carboxyl Protecting Groups Stability

  8. Benzyl ester 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 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 Bases: LDA NEt3, Py t-BuOK Others: DCC SOCl2 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Nucleophiles: RLi RMgX RCuLi Enolates NH3, RNH2 NaOCH3 Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Electrophiles: RCOCl RCHO CH3I Others: :CCl2 Bu3SnH Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Reduction: H2 / Ni H2 / Rh Zn / HCl Na / NH3 LiAlH4 NaBH4 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Oxidation: KMnO4 OsO4 CrO3 / Py RCOOOH I2, Br2, Cl2 MnO2 / CH2Cl2 Carboxyl Protecting Groups Stability

  9. 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 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 Carbonyl Protecting Groups Stability 1,3-Dioxanes 1,3-Dioxolanes

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

  11. 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-NR2 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 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 Amino Protecting Groups Stability Fmoc-NR Cbz-NR2 / Z-NR2

  12. Acetamide H2O: H2O: pH < 1, 100°C pH < 1, 100°C pH = 1, RT pH = 1, RT pH = 4, RT pH = 4, RT pH = 9, RT pH = 9, RT pH = 12, RT pH = 12, RT pH > 12, 100°C pH > 12, 100°C Bases: Bases: LDA LDA NEt3, Py NEt3, Py t-BuOK t-BuOK Others: Others: DCC DCC SOCl2 SOCl2 Nucleophiles: Nucleophiles: RLi RLi RMgX RMgX RCuLi RCuLi Enolates Enolates NH3, RNH2 NH3, RNH2 NaOCH3 NaOCH3 Electrophiles: Electrophiles: RCOCl RCOCl RCHO RCHO CH3I CH3I Others: Others: :CCl2 :CCl2 Bu3SnH Bu3SnH Reduction: Reduction: H2 / Ni H2 / Ni H2 / Rh H2 / Rh Zn / HCl Zn / HCl Na / NH3 Na / NH3 LiAlH4 LiAlH4 NaBH4 NaBH4 Oxidation: Oxidation: KMnO4 KMnO4 OsO4 OsO4 CrO3 / Py CrO3 / Py RCOOOH RCOOOH I2, Br2, Cl2 I2, Br2, Cl2 MnO2 / CH2Cl2 MnO2 / CH2Cl2 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 Amino Protecting Groups Stability Ac-NR2 Trifluoroacetamide Phthalimide

  13. Benzylamine p-Toluenesulfonamide, Tosylamide H2O: H2O: pH < 1, 100°C pH < 1, 100°C pH = 1, RT pH = 1, RT pH = 4, RT pH = 4, RT pH = 9, RT pH = 9, RT pH = 12, RT pH = 12, RT pH > 12, 100°C pH > 12, 100°C Bases: Bases: LDA LDA NEt3, Py NEt3, Py t-BuOK t-BuOK Others: Others: DCC DCC SOCl2 SOCl2 Nucleophiles: Nucleophiles: RLi RLi RMgX RMgX RCuLi RCuLi Enolates Enolates NH3, RNH2 NH3, RNH2 NaOCH3 NaOCH3 Electrophiles: Electrophiles: RCOCl RCOCl RCHO RCHO CH3I CH3I Others: Others: :CCl2 :CCl2 Bu3SnH Bu3SnH Reduction: Reduction: H2 / Ni H2 / Ni H2 / Rh H2 / Rh Zn / HCl Zn / HCl Na / NH3 Na / NH3 LiAlH4 LiAlH4 NaBH4 NaBH4 Oxidation: Oxidation: KMnO4 KMnO4 OsO4 OsO4 CrO3 / Py CrO3 / Py RCOOOH RCOOOH I2, Br2, Cl2 I2, Br2, Cl2 MnO2 / CH2Cl2 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 Amino Protecting Groups Stability Bn-NR2 Ts-NR2

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