1. RETROSYNTHETIC APPROCH TO ORGANIC SYNTHESIS PROTECTING GROUPS Dr. Shaikh S. Nizami Department of Chemistry University of Karachi

2. PROTECTING GROUPS

4. Definition NaBH 4 LiAlH 4 The ester cannot be directly reduced leaving the ketone unaffected

7. Protection of a ketone during reduction of an ester overall HOCH 2 CH 2 OH/H + LiAlH 4 H 3 O +

11. Acetals as protecting groups for alcohols (THP) + Tetrahydropyran (THP) H + or RCH 2 OTHP is stable to oxidation, reduction & base H 2 O/H + Deprotection Protection

12. Acetals as protecting groups for alcohols (MEM) + or Methoxethoxymethyl (MEM) RCH 2 OMEM is stable to oxidation, reduction & base H + Protection Deprotection

14. Benzyl ethers as protecting groups for alcohols + pyridine H 2 /Pd Benzyl ether is stable to base, mild acid, oxidation & reduction Protection Deprotection

15. t- Butyl ethers as protecting groups for alcohols + or H + Protection H 3 O + Deprotection t-Butyl ether is stable to base, mild acid, oxidation & reduction

16. PROTECTION OF ALCOHOLS 3. Use of silyl ethers + pyridine Protection or H + Deprotection Trimethylsilyl ether is stable to base, oxidation & reduction

17. PROTECTION OF ALCOHOLS 3. Use of silyl ethers Trimethylsilyl ethers are attacked by certain nucleophiles. To overcome this problem a number of more bulky trialkylsilyl protecting groups have been developed

18. Bulky trialkylsilyl protecting groups I II III I, Triisopropylsilyl ether (TIPSOR) II, t-Butyldimethylsilyl ether (TBDMSOR) III, t-Butyldiphenylsilyl ether (TBDPSOR)