If you run the reaction in DMF, the usage of imidazole as activator has no effect.

Try DMAP in dry DCM

I am surprised with the previous answer. Normally silylation requires silyl halide and a base (unless the solvent itself is a base like pyridine). Without the base the reaction will not proceed, or will proceed very slowly. Since DMF is apparently not a base, the presence of some sort of base is required.

Typical bases for silylation reactions are Et3N, imidazole, N-methytlimidazole, pyridine, etc.; in some cases DMAP needs to be added, usually in catalytic amount together with Et3N or i-Pr2NEt.

Inorganic base could also be used (like NaH, which might be helpful in your case), but this is not very common.

It also depends on the silyl group which you try to introduce (some silylated derivatives like TMS ethers are unstable). Numerous other conditions can be found in Geene's "Protective Groups".

Imidazole typically is not used as a base for this reaction but rather a nucleophilic additive to “activate“ the silyl chloride into silyl imidazolium cation. In inert solvent like DCM, additives such as imidazole or DMAP enhanced silylation reaction rate.

In DMF however, the addition of imidazole or DMAP do not affect the rate. You are right in that you still need base. Base is mainly used for catalyst turnover of DMAP or imidazole catalyst.

in reaction is run in DMF, the solvent itself acts as lewis base on silicon lewis acid and outcompetes imidazole/DMAP catalyst. Hence the addition of these catalysts has no effect in DMF

Greg,

Let’s clarify few things. First, imidazole and DMAP are bases, and as such always act like bases regardless of the solvent. Second, the role of the base in acylation and alkytation reactions is three-fold: a) general base catalysis; b) nucleophilic catalysis; c) scavenging of the acid, released during the reaction.

DMAP, pyridine and N-methylimidazole (not confuse it with just imidazole) are example of nucleophilic catalysts, Et3N and Hunig’s base are general base catalysts.

Believe me, bases are always required for either acylation or alkylation, even if the solvent is DMF. For a good overview of the role of bases in these reactions, I recommend to read the review published in Angew. Chem. Int. Ed., 1978, vol. 17, No 8, pp 569-583.

so for silylation reactions you typically need an alcohol, silyl chloride/triflate, bronsted base (for catalyst turnover... usually tertiary amine because its more basic than imidazole), and catalyic amount of a nucleophilic lewis base (imidazole, DMAP, etc.)

If the reaction is run in DCM solvent (or some other non-lewis basic solvent) the addition of the catalytic nucleophilic lewis base has drastic effect on reaction rate. If reaction is run in DMF, the DMF outcompetes the catalyst and thus the addition of catalyst has no effect on reaction rate. You are right in that you need still need bronsted base for reaction, but it doesnt have to be imidazole. In fact a hindered tertiary amine would probably be better.

Thats what I meant in my previous comment. Apologies for any confusion. I can provide reference if interested.

A New Reagent System for Efficient Silylation of Alcohols: Silyl Chloride-N-Methylimidazole-Iodine

Agnieszka Bartoszewicz, Marcin Kalek, Johan Nilsson, Renata Hiresova, Jacek Stawinski*

*Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, 10691 Stockholm, Sweden, Email: js📷organ.su.se

A. Bartoszewicz, M. Kalek, J. Nilsson, R. Hiresova, J. Stawinski, Synlett, 2008, 37-40.

DOI: 10.1055/s-2007-992379

This method never fails, recently tested on cleistenolide silylation.