Three-component formal metathesis via remote activating strategy enabled (RASE) domino activation of two C(sp3)–O bonds in alkyl ethers

Abstract

A remote activating strategy enabled (RASE) three-component formal metathesis among an alkyl benzyl ether, an alkyl aryl ether and a Brønsted acid is achieved through metal-free domino activation of two C(sp³)–O bonds in alkyl ethers under mild conditions, leading to dealkoxylative C(sp³)–N coupling products in good to excellent yields. With the use of in situ generated benzyl alkyl ether in this smooth metathesis, this chemistry offers an efficient strategy for direct site-selective introduction of pharmaceutically significant monocyclic thiazol-2(3H)-one scaffolds onto specific benzylic sites. A probable mechanism is also provided based on the results of control experiments and DFT calculations.