Synthetic return of the Meldrum’s acid. 2,2-dimethyl-1,3-dioxane- 4,6-dione assisted formation of tetrahydroquinolin-2-one derivatives. Short synthetic pathway to the biologically useful scaffold

Abstract

A new method for the preparation of tetrahydroquinolin-2-one derivatives has been described. The two-step reaction between enaminone and acylating agent followed by electrophilic cyclization can be performed in a single synthesis procedure, without isolation of intermediates. The whole process is facilitated by the use of acyl Meldrum’s acids which not only shortens the preparation time of the substrates but also easily extends the range of substituents used. Method scope and limitation were verified on various combinations of reagents and revealed general applicability of the method to the synthesis of tetrahydroquinolin-2-one core. Some exceptions to the regular course of the reaction were observed when a strongly EDG was introduced via acyl Meldrum’s acids, and the mechanism of this process was elucidated during the investigation.