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Boc Protection

(Boc2O + Base + DMAP)







Mechanism:



Boc protecion mechanism using base and DMAP


Steps:

  1. DMAP attacks a carbonyl site on di-tert-butyl dicarbonate (Boc2O) resulting in tert-butyl carbonate leaving as a leaving group.
  2. The amine attacks the carbonyl site on the boc-pyridinium species resulting in the release of DMAP (catalytic).
  3. The base (usually TEA or DIEA) picks up the proton from the protonated amine.
  4. tert-Butyl carbonate breaks down into CO2 (gas) and tert-butoxide.

Key Points:

  1. The reaction of DMAP with Boc2O is almost instantaneous (gas formation!). To avoid rapid gas formation slowly add the DMAP over an appropriate period of time.
  2. The CO2 gas that forms during the reaction should be allowed to escape. Don't run boc protections in closed systems.
  3. DMAP should accelate the rate of the boc protection reactions but also makes side reactions more likely.
  4. Base isn't needed for a boc protection reaction to progress (see Boc Protection Boc2O).
  5. tert-Butoxide is actually a stronger base than TEA (or DIEA) therefore in the end the proton should end up on tert-butoxide forming tert-butanol.