Home >
Community >
DMAP/Imidazole vs Triethylamine as acylation/silylation catlysts
Upvote
VOTE
Downvote
+ Organic
Posted by
Alan Turley
DMAP/Imidazole vs Triethylamine as acylation/silylation catlysts
I always thought of it in this fashion: imidazole or DMAP are somewhat nucleophilic and can attack the silicon center much better than TEA. They are also amine bases, so they can act as proton scavangers as well. I personally run such reactions with 2+ equivalents of imidazole instead of using imidazole and TEA. Both are cheap and easy to handle. I also, frankly, always felt that the amine attacks and displaces the chloride, rather than making a 5 bonded silicon anionic species (silylinium as you say?). I have heard of such anionic species being proposed as a SuFEx intermediate, but the idea is really the same for this.
Corey does comment on this as pgk said:
Quote
7: This process seems likely to proceed via N-dimethyl-tert-butylsilylimidazole, the conjugate acid of which can be expected to be a very reactive silylating agent.
I do have one point of contention with Corey's paper though. He states:
Quote
...the use of imidazole as catalyst and dimethylformamide as solvent proved to be exceedingly effective...
In my hands the use of DMF vs another polar aprotic solvents such as MeCN or THF to make TBDMS ethers was not important. I only used DMF where solubility of the starting material was an issue.
I always thought of it in this fashion: imidazole or DMAP are somewhat nucleophilic and can attack the silicon center much better than TEA. They are also amine bases, so they can act as proton scavangers as well. I personally run such reactions with 2+ equivalents of imidazole instead of using imidazole and TEA. Both are cheap and easy to handle. I also, frankly, always felt that the amine attacks and displaces the chloride, rather than making a 5 bonded silicon anionic species (silylinium as you say?). I have heard of such anionic species being proposed as a SuFEx intermediate, but the idea is really the same for this.
Corey does comment on this as pgk said:
Quote
7: This process seems likely to proceed via N-dimethyl-tert-butylsilylimidazole, the conjugate acid of which can be expected to be a very reactive silylating agent.
I do have one point of contention with Corey's paper though. He states:
Quote
...the use of imidazole as catalyst and dimethylformamide as solvent proved to be exceedingly effective...
In my hands the use of DMF vs another polar aprotic solvents such as MeCN or THF to make TBDMS ethers was not important. I only used DMF where solubility of the starting material was an issue.
Thanks for the responses. I actually was thinking in terms of basicity a bit too much. Now that Babcock_Hall pointed that out, in addition to the other comments I realize that TEA is fairly non nucleophilic (not as much so as DIPEA but still moreso than the rigid DMAP or Imidazole) and so that likely hinders its ability to attack the TBSCl as opposed to the catalystic bases.
Thanks for the responses. I actually was thinking in terms of basicity a bit too much. Now that Babcock_Hall pointed that out, in addition to the other comments I realize that TEA is fairly non nucleophilic (not as much so as DIPEA but still moreso than the rigid DMAP or Imidazole) and so that likely hinders its ability to attack the TBSCl as opposed to the catalystic bases.
The mechanism is not fully clarified yet. Even Prof. Corey himself (nobel prize awarded) who invented this reaction, “assumed” that the reaction proceeds via N-tert-butyldimethylsilylimidazole formation (but without putting his hand in the fire). J. Am. Chem. Soc., (1972), 94(17), 6190–6191 http://pubs.acs.org/doi/abs/10.1021/ja00772a043
The mechanism is not fully clarified yet. Even Prof. Corey himself (nobel prize awarded) who invented this reaction, “assumed” that the reaction proceeds via N-tert-butyldimethylsilylimidazole formation (but without putting his hand in the fire). J. Am. Chem. Soc., (1972), 94(17), 6190–6191 http://pubs.acs.org/doi/abs/10.1021/ja00772a043
Other people here probably have more practical experience; however, I would like to make a general point. For a chemical species to be an effective nucleophilic catalyst, it must be both a good nucleophile and a good leaving group. You seem to be saying something similar to this, but your emphasis is on basicity.
Other people here probably have more practical experience; however, I would like to make a general point. For a chemical species to be an effective nucleophilic catalyst, it must be both a good nucleophile and a good leaving group. You seem to be saying something similar to this, but your emphasis is on basicity.
Corey does comment on this as pgk said:
Quote
I do have one point of contention with Corey's paper though. He states:
Quote
In my hands the use of DMF vs another polar aprotic solvents such as MeCN or THF to make TBDMS ethers was not important. I only used DMF where solubility of the starting material was an issue.
Corey does comment on this as pgk said:
Quote
I do have one point of contention with Corey's paper though. He states:
Quote
In my hands the use of DMF vs another polar aprotic solvents such as MeCN or THF to make TBDMS ethers was not important. I only used DMF where solubility of the starting material was an issue.
More
VOTE
Thanks so much!
Thanks so much!
More
VOTE
Even Prof. Corey himself (nobel prize awarded) who invented this reaction, “assumed” that the reaction proceeds via N-tert-butyldimethylsilylimidazole formation (but without putting his hand in the fire).
J. Am. Chem. Soc., (1972), 94(17), 6190–6191
http://pubs.acs.org/doi/abs/10.1021/ja00772a043
Even Prof. Corey himself (nobel prize awarded) who invented this reaction, “assumed” that the reaction proceeds via N-tert-butyldimethylsilylimidazole formation (but without putting his hand in the fire).
J. Am. Chem. Soc., (1972), 94(17), 6190–6191
http://pubs.acs.org/doi/abs/10.1021/ja00772a043
More
VOTE
More
VOTE