Synthesis of Physostigmine

Question

I am trying to break down the synthesis of Physostigmine. In steps 9 and 10 in this synthesis picture https://en.wikipedia.org/wiki/Physostigmine#/media/File:Julian_synthesis.gif, how is the Et removed from the oxygen by AlCl₃ and the oxygen protonated? I thought about Friedel-Crafts Acylation but that doesn't seem right.

 

 

Answer 1

AlCl3 acts the same way as BCl3. In the first step, AlCl3 binds to the ether moiety leading to the switterionic alkoxonium aluminate complex:

 

Ph-OEt + AlCl3 --> Ph-O(Et)(AlCl3)

 

at this point you have formed an excellent leaving group (PhO-AlCl3) and because of the proximity between the chloride ligands to the ethyl group, a concerted Sn2 reaction takes place forming dichlorophenoxoaluminum and ethyl chloride:

 

Ph-O(Et)(AlCl3) --> PhO-AlCl2 + EtCl

 

Finally, upon proper work-up with water you will acquire a proton leading to your product and precipitate aluminum in the form of Al2O3.