Which reagent out of n-BuLi, t-BuLi and LDA will give 100% clean lithiated product 3-thiophenyl lithium, when reacted with 3-bromothiophene.
Personally, I will go for n-BuLi as it is a bromo derivative you will not have problem.Why not t-BuLi, for safety reason...And LDA will probably cause you problem of metalation in position 2.
LDA won't work at all and will probably deprotonate at position 2 as mentioned.
Mechanistically you want Lithium halogen exchange to form a more stable anion, with n-BuLi this gives Butyl bromide which can react with your system in an SN2 fashion to give useless 3-butyl thiophene. Usually it is fine but it sometimes it can be problematic
For lithium halogen exchange, to be certain you should use 2 equivalents of t-BuLi at -78 degrees, generally takes about an hour.
The first equivalent undergoes Li-halogen exchange and the second equivalent of t-BuLi causes E2 elimination of the t-BuBr side product to produce unreactive isobutylene. If you don't use two equivalents the desired thiophenyllithium may cause the E2 elimination giving you thiophene.
2 equivalents of t-BuLi is your best choice for 100% clean lithiated product. Take proper safety precautions. The biggest risk is having the needle come off the end of the syringe. Gas tight glass syringes with luer locks and an argon atmosphere are recommended.
I think the t- BuLi is best reagent in this reaction, use 2 equivalents of t-BuLi at -78 degrees.
n-BuLi is the best reagent for lithiation of 3-Bromothiophene with dry THF as the solvent at-78C.
We carried out this bromo/lithium exchange several times using 2 eq of tert-BuLi at
-70°C in THF. After addition of an electrophile usualy the yields are >90%. With LDA you get metalation in pos. 2 and at temperatute > -50°C elimination of LiBr to arene with following uncontrolled reactions. With n-BuLi the halogen/lithium exchange also takes place at low temperature but a few by-products are formed (< 2% metalation in position 2 and possible addition of a small amount of C4H9-Br; furthermore a few unknown impurities --> yield after addition of an electrophile
It is difficult to pevent nucleophilic attack of thienyl lithium to alkyl bromide. You may try direct metalation with Lithium metal in dry ether or THF at low temperature, instead of butyllithium as Lithiation reagent.
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