Protective groups

• How to protect -OH groups?

  ethers, silylethers, mixed acetals
• What ethers are used to protect -OH group?

  methy-l, tert-butyl-, benzyl-, triphenylmethyl-
• Methyl-ethers to protect -OH group:

  Stable towards acids, bases and redox reactions. Deprotection with Me3SiI, BBr3, (HI,HBr)
• Tert-butyl ethers to protect -OH group:

  Deprotection easily with 4M HCl, TEA.
• Benzyl-ethers to protect -OH group:

  Stable towards bases and mid. acids. Deprotection with catalytic hydrogenation, strong acids, Lewis acids, oxidation of -CH2- with hydrolysis.
• Triphenylmethyl-ethers to protect -OH group:

  Deprotection with HOAc, HCOOH, ZnBr2.
• Mixed acetals to protect -OH group

  MOM, MEM, THP
• MOM

  Methoxymethyl, mixed acetal. Deprotection with HCl, TsOH, Me3SiBr.
• MEM

  Methoxyethoxymethyl, mixed acetal. Deprotection with HCl, Lewis acid (no water).
• THP

  Tetrahydropyranyl, mixed acetal. Deprotection with TsOH, HOAc. Drawback: new chiral center is formed.
• Silyl ethers to protect -OH group.

  TMS, TBDMS, TIIPS
• TMS

  Trimethylsilyl. Labile under weak acids and bases.
• TMS (TBDMS)

  Tertbutyldimethylsilyl. Relatively stable under acids and bases. Doesn't react with common redox reagents. Protection 1°>2°>3°
• TIIPS

  Triisopropylsilyl. Stable under bases and acids. Doesn't react with strong nucleophiles. Selective protection of 1° in the presence of 2°-OH.
• Protection of carbonyl group

  cyclic acetals, cyclic thioacetals
• Cyclic acetals

  Protection of carbonyl group. Ethylene-glycol + H+, deprotection with acidic hydrolysis.
• Cyclic thioacetals

  Protection of carbonyl group. Reaction in acidic conditions. Deprotectio with aq. solution of Ag+, Cu(2+) or Hg(2+) salts. Stable under acids and bases.
• Cleavage of ethylene acetals

  TsOH + water; 5% HCl in THF
• Catalysts of acetalization

  TsOH, BF3.OEt2
• Protection of carboxyl group

  esters, oxazolines
• Esters to protect carboxyl group

  Benzyl-, methyl-, tert-butyl-. To avoid reactions with bases. Deprotection with Me3SiI.
• Oxazolines to protect carboxyl group

  To avoid reactions with RMgX and LiAlH4. Deprotection with acidic hydrolysis.

  
• Tert-butyl esters

  Protection of carboxyl group. Easy deprotection with TFA, HCOOH, TsOH.
• Methyl esters

  Protection of carboxyl group. Deprotection: Nu under neutral conditions (LiI, NaI,...), LiOH
• Benzyl esters

  Protection of carboxyl group. Deprotection with catalytic or transfer hydrogenation.
• Esterification

  The reaction of an alcohol with a carboxylic acid to produce an ester and water.

  
• Protection of thiols

  Benzyl group, N,S-acetals.
• Benzyl group.

  Protection of thiols. RSH + PhCH2Br + base. Deprotection: Hg(2+) + TFA + H2S or HF, anisol or Na, NH3 (l).
• N,S-acetals

  Protection of thiols. RSH + R'CONHCH2OH. Deprotection Ag(+) or Hg(2+) in TFA.
• Protection of diols

  As cyclic acetals. Reaction with a RCHO..
• Protection of carbamates

  Boc, Cbz, Fmoc
• Fmoc

  Fluorenylmethoxycarbonyl. Stable under acids. Deprotection with piperidine, Bu4N(+)F(-), bases.

  
• Boc

  Tert-butoxycarbonyl. Stable under bases, doesn't react with H2/cat. Deprotection with TFA in CH2Cl2, HCl, TsOH, Me3SiCl

  
• Cbz

  Benzyloxycarbonyl. Deprotection H2/cat., transfer hydrogenation, Py/HF + anisole, TFA.

  
• Protection of amides

  RNH2 + (RCO)2O/RCOCl + base. Deprotection with basic hydrolysis, NaBH4 (for CX3CO-groups).