The Friedel-Crafts Reaction Of Indoles With N-sulfonyl Aldimines

Indole-alkaloids are so far the most popular alkaloids isolated from the natural world. The synthesis of 3-substituted indole derivatives has attracted much attention, due to the diversity of various indole alkaloids skeleton and functional groups, and a variety of biological characteristics, especially as the building blocks for the synthesis of many natural products and other biologically active compounds. The catalyzed the Friedel–Crafts amidoalkylation of indoles with imines have turn out to be an effective method for the preparation of 3-indolylmethanamine derivatives. This thesis is focused on the development of synthetic method of 3-substituted indole derivatives including the optical active and none optical active product, which is divided into two parts:Part I, Asymmetric Friedel-Crafts addition of indoles to N-sulfonyl aldimines.Firstly, Chiral N-sulfinyl prolinamide was used as a catalyst for the Friedel–Crafts amidoalkylation of indoles with imines for the preparation of 3-indolyl methanamine derivatives. Secondly, asymmetric Friedel-Crafts reaction of indoles with imines was conducted by using chiral N-sulfinyl prolinamide or other chiral ligands and copper（II） salt as catalysts. Finally, the asymmetric Friedel-Crafts reaction of indoles with imines was conducted with chiral auxiliary. Unfortunately, all attempts were failed to afford any optical active product.Part II, Cu（OTf）₂ and N-sulfinyl prolinamide catalyzed Friedel-Crafts reaction of indoles with N-sulfonyl aldimines.Usually, preparation of 3-indolyl methanamine derivatives from the FriedelCrafts reaction of indoles and N-sulfonyl aldimines are difficult, because the major product is bis（indolyl）methane compound. In order to get 3-indolylmethanemine derivatives efficiently, a highly efficient and selective Friedel-Crafts amidoalkylati on reaction of indoles with N-sulfonyl aldimines has been developed utilizing Cu（OTf）₂ and N-sulfinyl prolinamide as the catalysts. This method provided a facile and cost –effective process for preparation of 3-indolyl methanamine derivatives in good to excellent yields（65-93%）. This method exhibited several features such as low catalyst consumption, mild reaction condition, simple operation and high efficiency.