278167-43-4Relevant articles and documents
Highly regioselective synthesis of 3,4-disubstituted 1H-pyrrole
Liu, Jian-Hui,Chan, Ho-Wai,Wong, Henry N. C.
, p. 3274 - 3283 (2007/10/03)
A highly regioselective method for the synthesis of 3,4-disubstituted 1H-pyrroles has been developed employing the ipso-directing property of a trimethylsilyl group. As a key starting material in this study, the known 3,4-bis(trimethylsilyl)-1H-pyrrole (3), was protected with carefully chosen groups, namely tert-butoxycarbonyl, N,N-dimethylaminosulfonyl, p- toluenesulfonyl, and triisopropylsilyl. A highly regioselective monoiodination of these 1-protected pyrroles was achieved by reaction with iodine - silver trifluoroacetate at low temperatures. Subsequent palladium- catalyzed cross-coupling reactions afforded 1-protected-4-substituted 3- trimethylsilyl-1H-pyrroles, which again underwent further room-temperature ipso-iodination and palladium-catalyzed cross-coupling reactions to provide symmetrical and unsymmetrical 1-protected-3,4-disubstituted 1H-pyrroles. Deprotection of 1-(tert-butoxycarbonyl) and 1-(N,Y-dimethylaminosulfonyl) groups was found to be nontrivial. The 1-(p-toluenesulfonyl) protecting group was eventually proved to be superior to other protection groups, because it was readily removed after stepwise ipso monoiodinations and palladium- catalyzed cross-coupling reactions.
