Boryl radical catalysis enables asymmetric radical cycloisomerization reactions

The development of functionally distinct catalysts for enantioselective synthesis is a prominent yet challenging goal of synthetic chemistry. In this work, we report a family of chiral N -heterocyclic carbene (NHC)–ligated boryl radicals as catalysts that enable catalytic asymmetric radical cycloisomerization reactions. The radical catalysts can be generated from easily prepared NHC-borane complexes, and the broad availability of the chiral NHC component provides substantial benefits for stereochemical control. Mechanistic studies support a catalytic cycle comprising a sequence of boryl radical addition, hydrogen atom transfer, cyclization, and elimination of the boryl radical catalyst, wherein the chiral NHC subunit determines the enantioselectivity of the radical cyclization. This catalysis allows asymmetric construction of valuable chiral heterocyclic products from simple starting materials. A good catalyst must bind tightly enough to reactants to bias their reactivity but then loosen its grip sufficiently to release the products. Radical catalysts with unpaired electrons are rare, in large part because the release step is too unfavorable. C.-L. Wang et al . now report that boron radicals, generated in situ from boranes bound to chiral carbene ligands, can achieve this balancing act as effective asymmetric catalysts for the cyclization of alkyne compounds, forming a variety of nitrogen heterocycles of interest in medicinal chemistry research. —Jake S. Yeston In situ generated boryl radicals with chiral N-heterocyclic carbene ligands catalyze asymmetric cycloisomerization reactions