Remote Radical 1,3-, 1,4-, 1,5-, 1,6- and 1,7-Difunctionalization Reactions

Abstract

Radical transformations are powerful in organic synthesis for the construction of molecular scaffolds and introduction of functional groups. In radical difunctionalization reactions, the radicals in the first functionalized intermediates can be relocated through resonance, hydrogen atom or group transfer, and ring opening. The resulting radical intermediates can undertake the following paths for the second functionalization: (1) couple with other radical groups, (2) oxidize to cations and then react with nucleophiles, (3) reduce to anions and then react with electrophiles, (4) couple with metal-complexes. The rearrangements of radicals provide the opportunity for the synthesis of 1,3-, 1,4-, 1,5-, 1,6-, and 1,7-difunctionalization products. Multiple ways to initiate the radical reaction coupling with intermediate radical rearrangements make the radical reactions good for difunctionalization at the remote positions. These reactions offer the advantages of synthetic efficiency, operation simplicity, and product diversity.

C‐Centered radical intermediates for C(sp3)‐H bonds functionalization: An emerging approach towards alkyl thiocyanates

“…This section will focus on the site-selective thiocyanation of unactivated C(sp 3 )À H bond via a 1,5-Hydrogen Atom Transfer. [72][73][74][75][76][77][78] This approach enables the selective functionalization of a distal CÀ H bond. A reactive open-shell intermediate initiates an intramolecular hydrogen atom transfer from a distal CÀ H bond to the reactive radical center.…”

Photoinduced radical tandem annulation of 1,7-diynes: an approach for divergent assembly of functionalized quinolin-2(1H)-ones

“…Among these, quinolin-2(1H)-one and its analogs are an important class of nitrogen-containing heterocycle scaffolds and are widely encountered in a myriad of pharmaceutical molecules and synthetic compounds ( Sliskovic et al, 1991 ; Suzuki et al, 2001 ; Bach et al, 2002 ; Kuethe et al, 2005 ) which display versatile biological and pharmacological activities ( McQuaid et al, 1992 ; Michael, 1995 ; Peifer et al, 2008 ), such as P2X7 receptor antagonist, rebamipide, and MAP kinase inhibitor ( Figure 1 ) ( Maignan et al, 2016 ; Tan et al, 2016 ; Miliutina et al, 2017 ; Wu et al, 2020 ). Various synthetic strategies have been achieved to construct the skeleton of such heterocycles, including Knorr synthesis ( Liu et al, 2012 ; Ma et al, 2023 ), Friedlander reactions ( Han et al, 2012 ), radical cyclization of acyclic precursors ( Kadnikov and Larock, 2004 ; Manley and Bilodeau, 2004 ), and other methods ( Fujita et al, 2004 ; Tsuritani et al, 2009 ; Berrino et al, 2012 ; Mai et al, 2014 ). The investigation of straightforward, atom-economic, environmentally acceptable, and green synthetic approaches to the construction of highly functionalized quinolin-2(1H)-ones remains a long-standing target and an active field of research in synthetic and medicinal chemistry.…”

Photocatalytic Multicomponent Annulation of Amide-Anchored 1,7-Diynes Enabled by Deconstruction of Bromotrichloromethane

“…Visible light-induced photoredox catalysis (VLPC) has been confirmed as one of the most attractive and powerful protocols for initiating various radical chemistry to construct a plethora of complex organic molecules because of its intrinsic characteristics of greenness, availability, safety as well as sustainability [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. This type of reaction provides a unique and direct way to construct intricate architectures that cannot be obtained by thermal processes [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ].…”