Coquière David, Cadeau Hélène, Rondelez Yannick, Giorgi Michel, Reinaud Olivia
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR CNRS 8601, Université René Descartes, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
J Org Chem. 2006 May 26;71(11):4059-65. doi: 10.1021/jo052605p.
In our quest for the elaboration of supramolecular models of metallo-enzyme active sites, we became interested in developing new methodologies for the selective functionalization of the large rim of calix[6]arenes. Here, we describe a novel reaction, i.e. the ipso-chlorosulfonylation of calixarene derivatives. The process has been found to be highly efficient, selective and versatile. The regioselectivity is controlled by the nature of the O-substituents at the small rim. Indeed, when O-alkylated by a protonable imidazole group, the aromatic rings are deactivated toward an electrophilic attack and the anisol units can be selectively ipso-chlorosulfonylated under mild conditions (rt). Performing the reaction at a higher temperature allowed the per-chlorosulfonylation to take place. Hence, the synthesis of various sulfonate and sulfonamide derivatives is reported. Finally, a combination of ipso-nitration and chlorosulfonylation allows the per-functionalization of the aromatic units at the large rim in selective alternate positions. Overall, this novel methodology opens new routes to a variety of calixarenes, allowing the tuning of their physical properties without drastically altering their hydrophobic conic cavities.
在我们致力于构建金属酶活性位点的超分子模型的过程中，我们对开发用于杯[6]芳烃大环选择性功能化的新方法产生了兴趣。在此，我们描述了一种新颖的反应，即杯芳烃衍生物的本位氯磺酰化反应。已发现该过程高效、选择性高且用途广泛。区域选择性由小环上的O - 取代基的性质控制。实际上，当通过可质子化的咪唑基团进行O - 烷基化时，芳环对亲电攻击失去活性，并且在温和条件下（室温），苯甲醚单元可以被选择性地本位氯磺酰化。在较高温度下进行反应可实现全氯磺酰化。因此，报道了各种磺酸盐和磺酰胺衍生物的合成。最后，本位硝化和氯磺酰化的组合使得能够在大环上的芳环单元的选择性交替位置进行全功能化。总体而言，这种新颖的方法为各种杯芳烃开辟了新途径，能够在不大幅改变其疏水锥形空腔的情况下调节它们的物理性质。
