Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

The use of 1,3-diamino-2-propanol with competitive <i>N</i>- and <i>O</i>-nucleophilic centers in a three-component cyclization with ethyl 4,4,4-trifluoroacetoacetate and methyl ketones enables the synthesis to be carried out for octahydropyrido[1,2-<i>a</i>]pyrimidin-6-ones and hexahydrooxazolo[3,2-<i>a</i>]pyridin-5-ones, the preferential formation of which depends on the substituent in the methyl ketone component. Dual acid-base catalysis of the reactions with alkyl methyl ketones increases the regioselectivity in the synthesis of octahydropyrido[1,2-<i>a</i>]pyrimidinones. The cyclization with acetophenone is characterized by the regiospecific generation of these bicycles. The presence of three chiral centers in the synthesized bicycles, depending on the alkyl substituent, causes the formation of two to four diastereomers, the structure of which has been determined with ¹H, ¹⁹F, ¹³C, 2D ¹H-¹³C HSQC/HMBC, ¹H-¹H COSY/NOESY NMR and X-ray diffraction analysis.