Enantioselective syntheses of carbocyclic nucleosides 5′-homocarbovir, epi-4′-homocarbovir, and their cyclopropylamine analogs using facially selective Pd-mediated allylations

Carbocyclic nucleosides (−)-5′-homocarbovir and (+)-epi-4′-homocarbovir were prepared from an acylnitroso-derived hetero Diels-Alder cycloadduct. A kinetic enzymatic resolution generated an enantiopure aminocyclopentenol and Pd(0)-mediated decarboxylative allylations of allyl 2,2,2-trifluoroethyl malonates were used to install the 4′-hydroxyethyl groups. Late stage derivatization gave access to the cyclopropylamine analogs, (−)-5′-homoabacavir, and (+)-epi-4′-homoabacavir. All carbonucleoside target molecules were evaluated for antiviral activity.