%0 Generic
%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/dataset/Synthesis_of_Thiophene_Based_TAK_779_Analogues_by_C_H_Arylation/2407858
%R 10.1021/jo400692p.s002
%2 https://acs.figshare.com/ndownloader/files/4047565
%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