Trimethylenemethane for Everyone: Convenient Preparation of the Nakamura-Yamago 1,3-Dipolar Reagent and an Effective Oxidative Transformation of Ketene Acetals

A convenient route to the Nakamura-Yamago methylenecyclopropane (MCP) precursor 1 to oxygen-stabilized, singlet trimethylenemethane (TMM) is reported, which avoids the hurdles of the original preparation procedure. An effective oxidation protocol is also introduced for converting the sensitive ketene acetals (KAs) from 1,3-dipolar cycloaddition of 1 to electron-poor olefins, into the corresponding α-hydroxyesters. The method, based on the use of dimethyldioxirane (DMDO) in acetone, affords fair to good yields (23–81%) for a number of KAs endowed with ketone, ester, or imide functional groups, as well as additional C─C double bonds. The utility of the protocol is further exemplified by the diastereoselective preparation of the Rokach-Galano-Durand bicyclic lactone rac-18, one of the most versatile building-blocks for the synthesis of isoprostanoidic derivatives.