Benzyne‐Induced Ring Opening Reactions of DABCO: Synthesis of 1,4‐Disubstituted Piperazines and Piperidines

Abstract

Abstract The 2‐(4‐phenylpiperazin‐1‐yl)ethan‐1‐amine scaffold is a structurally important motif that occurs frequently in medicinal and pharmaceutical chemistry. Despite the significance of this moiety, general strategies for its synthesis to date have required multistep methods and have been very limited, such as the use of S N Ar‐type reactions. Herein, we describe a synthetic methodology employing benzynes, 1,4‐diazabicyclo(2.2.2)octane (DABCO), and nitrogen nucleophiles to access these privileged organic compounds. The established protocol proved to be a transition‐metal‐free, mild reaction that proceeded via a quaternary ammonium salt formed from the benzyne and DABCO. magnified image