Synthesis of 5,6-trimethylenetetrahydro-1,3-oxazine-4-spirocyclopentanes and their acyclic precursors

Abstract

Tricyclic tetrahydro-1,3-oxazines-5,6-trimethylenetetrahydro-1,3-oxazine-4-spirocyclopentanes IV, V, and VII — were synthesized on the basis of 2-(1-isothiocyanatocyclopentyl)cyclopentanone (I). The reductive cyclization of the latter by the action of sodium borohydride leads to oxazinethione V; the acidic hydrolysis of I with subsequent reduction of amino ketone hydrochloride II with sodium borohydride and the reaction of isothiocyanato ketone I with lithium aluminum hydride make it possible to obtain 1,3-amino alcohols III and VI, respectively, which are converted to tetrahydro-1,3-oxazines IV and VII by cyclization with formaldehyde. Pyrimidinethione VIII was synthesized from isothiocyanato ketone I and methylamine. Compounds III–VII are mixtures of stereoisomers with predominance of the cis isomer.