NHC-Catalyzed Transition-Metal-Free Allylation of Aldehydes with MBH Carbonates and Their Michael Addition-Elimination-Cope Rearrangement Cascade: Facile Access to Sacubitril API

We report herein, a novel NHC-catalyzed transition-metal-free chemoselective allylation of aldehydes with Morita-Baylis-Hillman (MBH) carbonates using inorganic base. Fascinatingly, use of an organic base follows a different mechanism leading to highly functionalized 1,5-dienes via Michael addition-elimination reaction followed by [3,3]-sigmatropic cope rearrangement. The described method harnesses a new Csp2–Csp3 bond to access α-methylene-γ-oxo-γ-substituted ester derivatives paving a way to facile synthesis of potent natural products and APIs. A broad range of aromatic and aliphatic aldehydes with MBH carbonates were employed to provide a variety of interesting butanoate and dienyl ketone scaffolds in good to excellent yields. This chemistry has been extended to the efficient syntheses of sacubitril API and γ-butyrolactone scaffold found in many natural products and APIs.