NHC-Catalyzed Allylation of Aldehydes with MBH Carbonates and Their Michael Addition–Elimination-Cope Rearrangement Cascade: A Route to <i>rac</i>-Sacubitril

We report herein a novel NHC-catalyzed transition-metal-free chemoselective allylation of aldehydes with Morita-Baylis-Hillman (MBH) carbonates using an inorganic base. Fascinatingly, the use of an organic base follows a different mechanism, leading to highly functionalized 1,5-dienes via a 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 active pharmaceutical ingredients (APIs). A broad range of aromatic and aliphatic aldehydes with MBH carbonates was 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 <i>rac</i>-sacubitril API and γ-butyrolactone scaffold, which is a privileged core present in many natural products and APIs.