Hetero-Diels–Alder Addition of Ethyl 2-Nitrosoacrylate to (Z)-Prop-1-enyl Ethers. Stereoselective Synthesis of a Precursor to Sacubitril

Abstract A novel, conceptually distinct synthesis of a key precursor to sacubitril, an antihypertensive drug, is presented. The well-demonstrated hetero-Diels–Alder addition of in situ generated nitrosoalkenes to electron-rich enol ethers was engaged to establish the required functionalities with controllable relative stereochemistry. An asymmetric variant of the enol ether enabled access to the target molecule in enantiopure form.