Highly regioselective synthesis of 3,4-disubstituted 1H-pyrrole.
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, N-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.
Liu
J H
JH
Department of Chemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Chan
H W
HW
Wong
H N
HN
D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D011758:Pyrroles