%0 Journal Article %A Junker, Anna %A Yamaguchi, Junichiro %A Itami, Kenichiro %A Wünsch, Bernhard %D 2013 %T Synthesis of Thiophene-Based TAK-779 Analogues by C–H Arylation %U https://acs.figshare.com/articles/journal_contribution/Synthesis_of_Thiophene_Based_TAK_779_Analogues_by_C_H_Arylation/2407852 %R 10.1021/jo400692p.s001 %2 https://ndownloader.figshare.com/files/4047562 %K thiophene system 2 %K iodoarene %K amides 1 %K HATU %K catalyst systems %K reactive positions %K Ir catalyst %K synthesis %K Crabtree catalyst %K reaction times %K TAK %K arylated regioselectively %X A rapid synthesis of thiophene-based TAK-779 analogues 1 is reported using a late-stage diversification strategy. At the end of the synthesis, the key building block 2, which was prepared in six steps from thiophene, was arylated regioselectively at the α-position directly with iodoarenes. Since 2 offers several reactive positions, various established catalyst systems were tested. It was found that Crabtree catalyst (an Ir catalyst) converted efficiently and selectively the thiophene system 2 into 2-aryl-substituted compounds 9. The direct C–H arylation of 2 with electron-rich iodoarenes led to high yields, whereas electron-deficient iodoarenes required longer reaction times for complete conversion. A small set of diverse amides 1 was synthesized by hydrolysis of 9 and subsequent HATU coupling with primary amines 4. %I ACS Publications