| Autor: |
Sedillo K; Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States., Fan F; Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States., Knowles RR; Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States., Doyle AG; Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States. |
| Abstrakt: |
Catalytic intermolecular olefin hydroamination is an enabling synthetic strategy that offers direct and atom-economical access to a variety of nitrogen-containing compounds from abundant feedstocks. However, despite numerous advances in catalyst design and reaction development, hydroamination of N-H azoles with unactivated olefins remains an unsolved problem in synthesis. We report a dual phosphine and photoredox catalytic protocol for the hydroamination of numerous structurally diverse and medicinally relevant N-H azoles with unactivated olefins. Hydroamination proceeds with high anti-Markovnikov regioselectivity and N -site selectivity. The mild conditions and high functional group tolerance of the reaction permit the rapid construction of molecular complexity and late-stage functionalization of bioactive compounds. N-H bond activation is proposed to proceed via polar addition of the N-H azole to a phosphine radical cation, followed by P-N α-scission from a phosphoranyl radical intermediate. Reactivity and N -site selectivity are classified by azole N-H BDFE and nitrogen-centered radical spin density, respectively, which can serve as a useful predictive aid in extending the reaction to unseen azoles. |
