A five-step synthesis of 4-(1-mesyloxyethyl)-6-methyl-5-tosyl-1,2,3,4-tetrahydropyrimidin-2-one via amidoalkylation has been developed. Reaction of this compound with C-, O-, S-, and N-nucleophiles led to the highly diastereoselective formation of polysubstituted 2,3,4,5-tetrahydro-1H-1,3-diazepin-2-ones as a result of ring expansion. The diastereoselectivity of the reaction depended on the nucleophile used and changed from cis to trans. The results obtained were explained by the formation of a bicyclic cyclopropane intermediate followed by cleavage of the zero bridge and stereoselective addition of the nucleophile to the resulting dihydro-1H-1,3-diazepin-2-one under kinetic control. The prepared cis-4-alkoxy-5-methyldiazepines reacted with alcohols under acidic conditions to give thermodynamically more stable trans-isomers.
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Diastereoselectivity in the Ring Expansion of Tetrahydropyrimidin-2-ones into Tetrahydro-1H-1,3-diazepin-2-ones
Published:
30 October 2015
by MDPI
in The 19th International Electronic Conference on Synthetic Organic Chemistry
session General Organic Synthesis
Abstract:
Keywords: Tetrahydropyrimidin-2-ones; Tetrahydro-1H-1,3-diazepin-2-ones; Amidoalkylation; Ring Expansion; Diastereoselectivity