The diastereomers (1'R*,2R*)- and (1'S*,2R*)-1-amino-2-(1'-hydroxypiperidinebenzyl) and 1-amino-2-(1-hydroxy-1,1-diphenylmethyl) piperidine have been synthesized and transformed into the corresponding 4,4a,5,6,7,8-hexahydropyrido[1,2d][1,3,4]oxadiazines. Similarly to the unsubstituted parent compound 2-phenylhexahydropyrido[1,2d][1,3,4]oxadiazine, both the (4R*,4aR*)- and the (4S*,4aR*)-2,4-diphenylhexahydropyrido[1,2-d][1,3,4]oxadiazines were found to be predominantly in the trans-annellated conformation. This was concluded from low temperature NMR measurements, the chemical shift differences of the methylene protons adjacent to the bridged nitrogen, or the ΔH° values derived from ab initio calculations. In 2,4,4-triphenylhexahydropyrido[1,2-d][1,3,4]oxadiazine the conformational preference was switched to a slight predominance of the cis N-in conformation (53%). The conformational preference in the solid state for the (4R*,4aR*)- and the (4S*,4aR*)-2,4-diphenylhexahydropyrido[1,2-d][1,3,4]oxadiazines was the same as in solution. The 15N chemical shifts of the bridgehead nitrogens were found to correlate to some extent with the conformational preference, while no correlation was observed between the geminal coupling constant of the methylene protons adjacent to the bridgehead and the adopted ring annellation.
ASJC Scopus subject areas
- Chemical Engineering(all)