TY - DATA T1 - Synthesis of Thiophene-Based TAK-779 Analogues by C–H Arylation PY - 2013/06/07 AU - Anna Junker AU - Junichiro Yamaguchi AU - Kenichiro Itami AU - Bernhard Wünsch UR - https://acs.figshare.com/articles/dataset/Synthesis_of_Thiophene_Based_TAK_779_Analogues_by_C_H_Arylation/2407858 DO - 10.1021/jo400692p.s002 L4 - https://ndownloader.figshare.com/files/4047565 KW - thiophene system 2 KW - iodoarene KW - amides 1 KW - HATU KW - catalyst systems KW - reactive positions KW - Ir catalyst KW - synthesis KW - Crabtree catalyst KW - reaction times KW - TAK KW - arylated regioselectively N2 - 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. ER -