Weak bonding strategies for achieving regio- and site-selective transformations

Abstract

The ability to identify and transform selectively similar constitutional fragments in molecules in a predetermined direction over all other possible directions remains a fundamental challenge in relation to the growth and reach of synthetic chemistry. A rapidly emerging approach toward this goal is to leverage weak bonding interactions, including both noncovalent and dynamic covalent bonds to control regio- and site selectivities. Drawing inspiration from the reactions catalyzed by enzymes, chemists have developed a wide variety of weak bonding strategies to facilitate regio- and site-selective transformations without the need to introduce additional handles onto molecular frameworks. Here, by classifying these weak bonding protocols into four categories, namely, bond-destabilizing, masking, pre-organizing, and templating strategies, we summarize the advances that have been made during the past two decades, highlighting their relative simplicity in promoting regio- and site-selective reactions that would otherwise be difficult to perform on molecules.