The Asymmetric Mannich Reaction Of N-Boc C-alkynyl Imines And C3-Substituted Oxindoles

Mannich reaction is a important chemical reaction that can effectively build a C-C bond in organic chemistry. And oxindole derivatives have important applications in natural products and pharmaceuticals molecules. In this paper, we expound that organocatalytic asymmetric mannich reaction of C-alkynyl imine in situ generation from C-alkynyl N-Boc,O-acetal with C3-substituted oxindole(nucleophile) by chiral bifunctionnal tertiary-thiourea amine catalysts, and delightfully, we get a class of mannich base compounds which bearing an oxindole scaffold. Firstly, mannich reaction which is described and reported by different types of catalysts recently has also been summarized detailly. In the second part of this paper, research methods and results are expounded. In this paper, the reaction conditions of classical mannich addition reaction of oxindole derivatives with C-alkynyl-N-Boc,O-acetal were explored. The results have demonstrated that quinine thiourea catalyst could give super yield (94%) and high enantioselectivity (up to 92% ee), when the reaction proeeeded in toluene and 0.1 eq catalyst and reaction of 72h at the designation (75℃) temperature. From this, we had a wide substrate scope and they have a highly versatile. In conclusion, we found a suitable way to get the asymmetric mannich addition reaction between C-alkynyl N-Boc,O-acetal and C3-substituted oxindoles with a class of Mannich base products which having an oxindole scaffold and providing a new method for the synthesis of many drug molecules.