Iron-catalyzed peroxidation–carbamoylation of alkenes with hydroperoxides and formamides via formyl C(sp²)–H functionalization

Abstract

A reaction protocol in which FeCl and tert-butyl hydroperoxide facilitated a selective radical coupling reaction of aryl alkenes or 1,3-enynes with tert-butyl hydroperoxide and formamides to prepare an array of β-peroxy amides has been achieved. The β-peroxy amide could serve as a synthetic precursor which was facilely converted to β-hydroxy amide, β-keto amide and β-lactam following subsequent chemical transformation.

Iron-Catalyzed Carbamoylation of Enamides with Formamides as a Direct Approach to N-Acyl Enamine Amides

“…The application of this well-established protocol on unsaturated substrates, however, largely resulted in the hydrocarbamoylation adducts . Only two precedent exceptions have emerged for iron-catalyzed E -selective carbamoylation and carbo-oxygenation of styrenes which assembled α,β-unsaturated amides and β-peroxy amides, respectively. Inspired by the above studies, we speculated the feasibility of the direct coupling of enamides with formamides via aminoacyl radical species in which the stereoselectivity could be controlled by the amide moiety.…”

Propargyl Radicals in Organic Synthesis

“…This methodology was also extended to include 1,2-difunctionalization (carbamoylation and peroxidation) using Fe catalysis. [36] Propargyl radicals have also been used to access complex polycyclic structures. [37] Sherburn et al have used acyl radical addition to 1,3-enynes to generate propargyl/allenyl radicals during their studies on formal synthesis of (+)-himbacine (Scheme 16).…”

“…The resulting β‐peroxy alcohols could be further transformed into β‐hydroxyynones and propargylic 1,3‐diols. This methodology was also extended to include 1,2‐difunctionalization (carbamoylation and peroxidation) using Fe catalysis [36] …”

β‐Keto Amides: A Jack‐of‐All‐Trades Building Block in Organic Chemistry

“…γ , δ ‐Unsaturated β ‐keto amides are not easy to prepare because they may not endure common reaction conditions. In 2017, Cheng et al [106] . disclosed an iron‐catalyzed synthesis of β ‐peroxy amides from enynes 197 and TBHP.…”