Radicals force stubborn C bond

Abstract

Making molecules with quaternary carbon bonds—four carbons attached to a central C—is tricky but necessary for medicinal chemists. Quaternary C bonds have a discrete shape and fit “lock and key” into binding sites, Princeton University chemist David MacMillan says. But quaternary Cs are hard to synthesize because they’re so bulky. MacMillan and coworkers at Princeton and pharmaceutical firm Janssen-Cilag have figured out a fix using a radical reaction that scientists speculated wasn’t possible. In what’s called an S H 2 mechanism, the group used blue light and two catalysts to trigger the addition of a three-carbon radical to the end of a linear hydrocarbon ( Science 2021, DOI: 10.1126/science.abl4322 ). The reaction is highly selective and results in a new quaternary C bond. An S N 2 reaction, common in organic chemistry, is when one reactant attacks another, resulting in a new C bond. An S H 2 reaction is