Fluoroalkyl Iodides in Fluoroalkylative Difunctionalization of C−C Multiple Bonds

Abstract

Fluorinated alkyl iodides serve as a convenient and inexpensive source of fluoroalkyl radicals that can readily undergo addition to the CÀ C unsaturated bonds of alkynes and alkenes which is the foundation for a variety of useful synthetic protocols. Since 2010 this field has witnessed huge progress in several respects. First the portfolio of fluorinated alkyl iodides was extended beyond only simple perfluoroalkyl iodides (C n F 2n + 1 I). In particular, employment of iododifluoroÀ methyl-carbonyls and phosphonates has enabled facile installation of the medicinally relevant difluoromethylene motif. Secondly, from a conceptual point of view, novel strategies for activation of fluoroalkyl iodides towards radical formation have been introduced, relying on the formation of electron donor-acceptor (EDA) complexes, photoredox catalysis, frustrated Lewis pairs and transition metal catalysis, complementing prior approaches based on heat and UV induced CÀ I homolysis, radical initiators, and simple electron transfer processes. Based on these strategies a range of novel fluoroalkylative transformations of unsaturated systems have been added to classical iodoperfluoroalkylation. Broadly applicable protocols for simple fluoroalkylation and hydrofluoroalkylation, as well as for more sophisticated, complexitybuilding methods of fluoroalkylation-annulation and tandem multicomponent fluoroalkylations with concomitant installation of another functionality have been recently disclosed. This review summarizes the progress achieved since 2010 in the reactivity of fluoroalkyl iodides towards alkenes and alkynes with emphasis placed on the above-mentioned advances.1.

N-Heterocyclic Carbene and Manganese Synergistic Catalysis: A Three-Component Radical Acylmonofluoroalkylation of Alkenes

“…In line with its unique properties, a fluorine atom is found in half of the clinical drugs (Scheme a) . Among various fluorination protocols, significant efforts have been made within the context of catalytic difunctionalization of alkenes, as it enables a single-step enhancement of molecular complexity through the simultaneous installation of a fluorine-containing motif and another functionality. Stephenson and co-workers pioneered the atom transfer radical addition (ATRA) reaction of unactivated alkenes via photoredox catalysis to introduce monofluoroalkyl groups and a halogen atom.…”