Nucleophile-Mediated Ring Expansion of 5‑Acyl-substituted 4‑Mesyloxymethyl-1,2,3,4-tetrahydropyrimidin-2-ones in the Synthesis of 7‑Membered Analogues of Biginelli Compounds and Related Heterocycles

A general six-step approach to alkyl
2-oxo-2,3,6,7-tetrahydro-1H-1,3-diazepine-5-carboxylates
and 5-acyl-2,3,6,7-tetrahydro-1H-1,3-diazepin-2-ones
based on the nucleophile-mediated
ring expansion reaction of 5-functionalized 4-mesyloxymethyl-1,2,3,4-tetrahydropyrimidin-2-ones
has been developed. Synthesis of the latter involved nucleophilic
substitution of tosyl group in readily available N-[(2-benzoyloxy-1-tosyl)­ethyl]­urea with sodium enolates of β-oxoesters
or 1,3-diketones, followed by dehydration or heterocyclization-dehydration
of resulting products, removal of benzoyl protection, and conversion
of hydroxymethyl group into mesyloxymethyl group. Conformations of
the obtained tetrahydro-1H-1,3-diazepin-2-ones in
solid state and solutions were established using X-ray diffraction
and NMR spectroscopy. A plausible mechanism of tetrahydropyrimidine
ring expansion based on DFT calculation at B3LYP/6-31+G­(d,p) level
and NMR monitoring experiments was discussed. The ring contraction
reaction of methoxy- or phenylthio-diazepinones under acidic conditions
resulted in the corresponding 3-functionalized 1-carbamoyl-1H-pyrroles.