Lithiation of thiophenes

Lithiothiophene, arising from lithiation of thiophene with n-BuLi, was treated with iodine to give 2-iodothiophene, which was allowed to react with sodium malononitrile in the presence of catalytic PdCl2(Ph3P)2 to afford thienylmalononitrile 18. Interestingly, a-metalation of ethyl 3-... 

The lithiation of thiophene and its addition to ethylene oxide is a key step in the synthesis of the platelet aggregation inhibitor ticlopidine.91... 

Deprotonative zincation and magnesiation have been developed as alternatives for the lithiation of thiophenes. The drawbacks associated with lithiation are that it usually requires the reactions to be performed at —78°C, and the lithium derivatives so formed cannot he directly used for cross-coupling reactions. 

Stable bis(trimethylsilyl)thiophene 1,1-dioxides have been prepared by lithiation of thiophene followed by silyla-tion and oxidation with peracetic acid or MCPBA. These thiophenedioxides also undergo a [4- -2] Diels-Alder reaction with A -phenylmaleimide to produce monoadducts with elimination of sulfur dioxide (Scheme 31) <1994TL4425>. 

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