N‐Alkoxyphtalimides as Versatile Alkoxy Radical Precursors in Modern Organic Synthesis

Abstract

O-substituted derivatives of N-hydroxyphthalimide (NHPI) have attracted much attention recently as synthetically available, stable, and convenient reagents for the generation of free radicals under mild conditions. The single-electron reduction by a photoredox catalyst or another reagent results in the NÀ O bond cleavage of an NHPI derivative with the release of free radicals that undergo selective synthetic transformations. Whereas N-acyloxyphtalimides (NHPI esters) are well known as a convenient C-radical source due to the facile one-electron reduction followed by the decarboxylation, N-alkoxyphtalimides are much less studied as radical precursors. The present review shows that N-alkoxyphtalimides are effective reagents for free-radical transformations starting from the generation of alkoxy free radicals. Visible light induced reactions are discussed first, these processes are classified according to the way how intermediate alkoxy radicals transformed to C-centered radicals: via hydrogen atom transfer to oxygen atom (HAT, including 1,5-HAT, 1,2-HAT, and intermolecular HAT) or via β-scission. Other photochemical radical reactions of alkoxyphthalimides and nonphotochemical tin-mediated processes are discussed separately.

Recent Advances in N-O Bond Cleavage of Oximes and Hydroxylamines to Construct N-Heterocycle

“…Due to weak N-O σ bonds [ 5 ], the average energy of about 57 kcal/mol −1 , is far below the σ C-X (X = C, N, O), thus N-O bond units have been considered to be quite unstable bonds. Those N-O bond compounds are easy to break under the influence of a transition-metal catalyst, transition-metal-free catalyst, or photocatalyst, allowing the formation of new C-N, C-O, or C-C bonds to build nitrogen compounds (e.g., nitrogen-containing heterocycles [ 5 , 6 , 7 , 8 , 9 ], alkyl nitriles [ 10 , 11 , 12 ], and amines [ 13 ]), or oxygen-containing compounds [ 14 , 15 , 16 , 17 , 18 ]. Reactions involving N-O bond cleavage have a long history in organic synthesis.…”

CH‐Functionalization of Heterocycles with the Formation of C−O, C−N, C−S/Se, and C−P Bonds by Intermolecular Addition of Heteroatom‐Centered Radicals

“…Analogously to C‐centered radicals, they are added to unsaturated bonds with the formation of carbon‐heteroatom bonds [51–57] . However, hydrogen atom abstraction and β‐scission processes are also typical for heteroatom‐centered radicals, especially O‐centered [58,59] and N‐centered [56] ones, whereas not so frequently observed in C‐centered radical chemistry. Heteroatom‐centered radicals are capable of mediating atom or group transfer or can directly abstract a hydrogen atom from saturated C( sp 3 )−H bonds with the generation of C‐centered radicals [49,55–58,60–64] .…”

“…However, hydrogen atom abstraction and β‐scission processes are also typical for heteroatom‐centered radicals, especially O‐centered [58,59] and N‐centered [56] ones, whereas not so frequently observed in C‐centered radical chemistry. Heteroatom‐centered radicals are capable of mediating atom or group transfer or can directly abstract a hydrogen atom from saturated C( sp 3 )−H bonds with the generation of C‐centered radicals [49,55–58,60–64] . These reactions constitute a large family of advanced synthetic methods for the functionalization of C−H bonds [65–71] .…”

“…As the topic is broad, [33,46,47,49–51,56,58,79–84] the present review mainly focuses on addition reactions of heteroatom‐centered radical to heteroaromatic π‐systems (Scheme 1). However, papers, in which non‐aromatic heterocycles participate in the reaction, have been also reported, and some of them are mentioned here.…”

Photoredox-catalyzed, oxygen-directed unactivated δ-C(sp3)–H functionalization toward oxepanes

“…9 Elegant achievements on alkoxy radical-mediated distal C(sp 3 )–H functionalization can be found from Arigoni's seminal paper for the construction of tetrahydrofuran motifs with classic Barton reaction of alkyl nitrites (RONO) 10 to the most recent reports on photoredox-catalysed reactions. 11 N -Alkoxypyridinium salts, serving as a class of effective precursors of O-radicals, could allow position-selective C(sp 3 )–H functionalization reactions for the synthesis of δ-functionalized alcohols (Scheme 1b). 12 Of these reports, Hong and Baik reported the conversion of N -alkoxypyridinium salts to δ-pyridylated alcohols under photoredox-catalysed conditions.…”