Regiodivergent Synthesis of α- and β-Acyloxy Acrylates through Catalyst-Driven Migrations from α-Diazo-β-Acyloxy...

The synthetic versatility of α-diazo-β-acyloxy esters to selectively undergo metal-catalyzed 2,3-acyloxy or 1,2-hydride migration was evaluated. The type of migration was controlled by the catalyst, with rhodium(II) and copper(II) delivering α-acyloxy acrylates from 2,3-acyloxy migration, while silver(I) catalyzed the formation of regioisomeric β-acyloxy acrylates through 1,2-hydride migration. In addition to the good yields observed for 2,3-acyloxy migrations (56-95 %), the reactions exhibited remarkable chemo-, regio- and diastereoselectivity. The E : Z ratio was found to be excellent for Rh (20 : 1 or higher in most cases) and moderate to good for Cu (6-13 : 1 favoring E-isomer). In the case of Ag-catalyzed 1,2-hydride migration, the yield (60-93 %) and diastereoselectivity (7 : 1 to >20 : 1 favoring Z isomer) for β-acyloxy acrylates were also high, although the competitive formation of regioisomeric α-acyloxy acrylate was detected in minor amounts. Furthermore, both 1,2-hydride and 2,3-acyloxy migrations showed tolerance to functional groups, which were successfully explored in subsequent post-functionalization processes to access heterocyclic nuclei of pharmacological relevance. We also investigated the rhodium-catalyzed 2,3-acyloxy migration, with the support of computational chemistry, to unravel this reaction mechanism and to explain the factors influencing migratory assistance and diastereoselectivity.