Thiophenes lithiation with ortho assistance

Lithiation at a thiophene /3-position, in the presence of a free a-position, has been achieved with the assistance of an ort/io-directing substituent at C-lX Thiophene-2-carboxylic acid lithiates at C-3, via ortho assistance, using n-butyllithium, but at C-5, using lithium diispropylamide. 3-(Oxyalkyl)thiophenes, again with ortho assistance, are lithiated at C-2. The lithiation of 2-chloro-5-methoxythiophene at C-4 and C-3, in a ratio of 2 1, is instructive as is the deprotonation of 2- and 3-bromothiophenes at 5- and 2-positions respectively with LDA. The conversion of 3-isopropylthiophene into the 2-aldehyde by Vilsmeier formylation but into the 5-aldehyde via lithiation presents a nice contrast. ... 

Lithiation at a thiophene p-position, in the presence of a free a-position, has been achieved with the assistance of an ortho-dircciing substituent at C-2. A surprising degree of functionality can be tolerated in some lithiations. " ... 

Thiophene-2-carboxylic acid lithiates at C-3, via ortho assistance, using butyllithium, but at C-5 using lithium diisopropylamide. The lithiation of 2-chloro-5-methoxythiophene at C-4 and C-3, in a ratio of 2 1, is instructive. 2-and 3-Bromothiophenes undergo lithium-halogen exchange with w-butyllithium, but a-deprotonation with LDA. ... 

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