Chemical resolution of inherently racemic dihydropyrimidinones via a site selective functionalization of Biginelli compounds with chiral electrophiles: a case study

Lithiation/substitution of 4-aryl-6-methyl-3,4-dihydropyrimidin-2(1H)-one ester derivatives with n-BuLi can be directed selectively at N-3 or C-6 positions, depending upon nature and equivalents of the base used and ‘hardness or softness’ of the metalated site/electrophile used. Biginelli dihydropyrimidinone substrate appended with enantiopure N-protected l-phenylalanine amino acid chloride, at N-3 position after resolution and deprotection yielded both enantiomers of 3,4-dihydropyrimidinones.

Expeditiously metalated Biginelli 3,4-dihydropyrimidine-2(1H)-one (DHPM) derivatives, substituted with chiral auxiliaries (CA) at N-3 site, selectively, furnish access to enantiomerically pure DHPMs. However, appending CA at C-6 methyl did not allow clean separation of diastereomers.Figure optionsDownload as PowerPoint slide