Three-component Reactions Based On Trapping Of Active Ylides With Formaldehyde

A multi-component reaction (or MCR) is a chemical reaction where three or more compounds react to form a single product that incorporate substantial portions of all the components. Owing to the obvious advantages in generation of small organic molecules with structural diversity and complexity, multi-component reaction have been developed rapidly in the field of both basic research and chemical industry.In the past decade, a large number of compounds of structural diversity were prepared through trapping active ylides with aldehydes, ketones or imines. However, because the electrophilic reagents are usually activated aldehydes, ketones or imines from them, the reaction products are attached to a phenyl group or an activating group at the (3position. In this dissertation, we designed and implemented multi-component reactions of trapping of ylide by formaldehyde for the preparation of the product with structural diversity:efficient synthesis of a-aryl serine derivatives and3-substituted-3-hydroxymethyloxindoles via trapping ammonium/oxonium ylide with formaldehyde, and the anticancer activities of some three-component products were tested.In chapter1, the advantages of multi-component reactions in generation of small organic molecules with structural diversity, diazo chemistry, yilde chemistry, Synthesis of compounds of structural diversity through multi-component reactions based on trapping of active ylides with electrophile and related contents were briefly summarized. At the end of this chapter, we also introduced the designed strategies and a brief description of this dissertation.In chapter2, a three-component reaction of aryldiazoacetates, anilines and formaldehyde was reported. Although formaldehyde aqueous solution which is used as the electrophile could bring many competing reactions, the reaction selectively offered a-aryl serine derivatives and a-aryl threonine derivatives. It is the first time that trapping of ammonium ylides by aliphatic aldehydes was reported. Synthetic application of the three-component reaction for the preparation of hydroquinoxaline derivative was also demonstrated.In chapter3, we reported two three-component reactions of3-diazooxindoles with formaldehyde and anilines or water. Many components of formalin which is used as the electrophile could bring side reactions, but the reaction selectively offered3-amino-3-hydroxymethyloxindoles and3-hydroxy-3-hydroxymethyloxindoles. The anticancer activities of3-substituted-3-hydroxymethyloxindoles were tested and the preliminary results showed3-amino-3-hydroxymethyloxindole could inhibit the growth of SJSA-1cancer cell lines. In addition, the synthetic potential of this Rh(II)-catalyzed three-component strategy was demonstrated.In this dissertation, we also studied other aliphatic aldehyde, including acetaldehyde, propionaldehyde, butyraldehyde in ylide trapping reaction. And no good result was obtained. Early attempts to exploration of asymmetric version of the reactions does not get good results, and further research is still being through.