From Propargylic Alcohols to Substituted Thiochromenes: <i>gem</i>-Disubstituent Effect in Intramolecular Alkyne Iodo/hydroarylation

This work describes the 6-endo-dig cyclization of S-aryl propargyl sulfides to afford 2H-thiochromenes. The substitution at the propargylic position plays a crucial role in allowing intramolecular silver-catalyzed alkyne hydroarylation and N-iodosuccinimide-promoted iodoarylation. Additionally, a PTSA-catalyzed thiolation reaction of propargylic alcohols was developed to synthesize the required tertiary S-aryl propargyl ethers. The applicability of merging these two methods is demonstrated by synthesizing the retinoic acid receptor antagonist AGN194310.本研究报道了S-芳基炔丙基硫醚的6-内型-dig环化反应（6-endo-dig cyclization），用以制得2H-硫代色烯（2H-thiochromenes）。炔丙基位点上的取代基对于实现分子内银催化炔烃氢芳基化反应以及N-碘代琥珀酰亚胺（N-iodosuccinimide）促进的碘代芳基化反应具有关键作用。此外，本研究还开发了一种对甲苯磺酸（PTSA）催化的炔丙醇硫醚化反应，以合成所需的叔型S-芳基炔丙基醚。通过合成视黄酸受体（retinoic acid receptor）拮抗剂AGN194310，验证了将上述两种方法联用的适用性。