Radical new way to control chirality

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Nitrogen rings with attached chiral organic groups are common motifs in pharmaceuticals, agricultural chemicals, and bioactive small molecules. Medicinal chemists frequently seek to add chemical groups with specific chirality to nitrogen heterocycles, but their toolbox is limited. Reactions like catalytic asymmetric reduction can control enantioselectivity in nitrogen heterocycle additions, but typically require preinstalling reactive groups on the rings and multiple steps. An alternative is a free-radical addition called a Minisci-type reaction, but it is not enantioselective and often adds groups to several ring positions on the heterocycle. Robert J. Phipps and grad students Rupert S. J. Proctor and Holly J. Davis at the University of Cambridge now propose a fix for those drawbacks. They developed a Minisci-type reaction that uses two catalysts to add N-acyl α-amino alkyl radicals to nitrogen heteroarenes (Science 2018, DOI: 10.1126/science.aar6376). The approach creates a chiral center enantioselectiv...