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[摘要]：Direct CH bond arylation in the a- and beta-positions of spirocyclic thiophenes containing various functional groups (amine, ether, acetal, lactone) was accomplished. Selective phenylation in the a-position of the thiophene ring was achieved by using the catalytic system PdCl2/bipy/Ag2CO3. The introduction of phenyl moieties to the beta-position was performed with the catalytic system PdCl2/P[OCH(CF3)2]3/Ag2CO3. Even the five-membered lactone 10 with an electron-withdrawing carbonyl moiety directly attached to the thiophene ring was arylated. Spirocyclic thiophenes substituted with a phenyl moiety in position A (top position) or B (left position) display low nanomolar s1 affinities (e.g., 4a: Ki = 1.6 nM; 5a: Ki = 2.4 nM), indicating an additional hydrophobic pocket on the complementary s1 receptor protein. A phenyl moiety in position C (at the bottom position) is not tolerated by the s1 receptor (e.g., 12: Ki = 483 nM). However, an additional phenyl moiety in position A is able to compensate at least partially the unfavorable effects of the phenyl moiety in position C. |
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