Visible-Light-Mediated Iodoperfluoroalkylation of Alkenes in Flow and Its Application to the Synthesis of a Key Fulvestrant Intermediate

Org Lett. 2019 Jul 5;21(13):5341-5345. doi: 10.1021/acs.orglett.9b01992. Epub 2019 Jun 21.

Abstract

Two efficient continuous flow iodoperfluoroalkylation methods are described: using 0.05 mol % perylene diimide (PDI) photocatalyst under 450 nm irradiation or substoichiometric triethylamine under 405 nm irradiation. These methods enable dramatically elevated productivity versus batch processes. The triethylamine-mediated method is explored mechanistically and in substrate scope. The gram-scale synthesis of an active pharmaceutical ingredient side chain is also reported in flow, via a photochemical iodoperfluoroalkylation followed by hydrogenolysis.

Publication types

  • Research Support, Non-U.S. Gov't