Efficient synthesis of protected cyclopropyl β-aspartylphosphates†
Abstract
The in situ reaction of protected dehydroamino acids with derivatives of vinyldiazomethane leads to good to excellent yields of vinyl cyclopropanes via 3 + 2 dipolar cycloaddition followed by N2 extrusion. Chromatographic separation of the cyclopropane diastereomeric products, followed by characterisation by 1H NMR and X-ray crystallography allowed the cis and trans diastereomers to be easily identified. Oxidative cleavage of the vinyl moiety then led directly to protected cyclopropane aspartic acid derivatives in three steps from commercially available materials. These compounds were converted to protected methylenephosphonate, difluoromethylenephosphonate and phosphoramidate analogues of β-aspartyl phosphate.