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 nitroso alkenes to electron rich enol ethers is engaged to establish the required functionalities with controllable relative stereochemistry. An asymmetric variant of the enol ether enables the access to the target molecule in enantiopure form.

Stereospecific Cu(I)-Catalyzed C–O Cross-Coupling Synthesis of Acyclic 1,2-Di- and Trisubstituted Vinylic Ethers from Alcohols and Vinylic Halides

“…Vinylic ethers are electron-rich alkenes with applications including [3.3]-Claisen rearrangements, cyclization and cycloaddition processes, , and bioorthogonal reactions . Plasmalogen phospholipid natural products feature acyclic ( Z )-1,2-disubstituted vinylic ethers .…”