that have developed cascade reactions between electron‐poor O‐acyl oximes 25 and styrenyl boronic acids 26 (Scheme 2.7) [29]. This reactivity was also based on the generation of an iminyl radical by reductive SET from a photoexcited catalyst, its following transposition by 1,5‐HAT, and the reaction of the corresponding distal carbon radical with the olefin. Although the methodology was only used to install styrenyl‐type substituents, it enabled the fast assembly of small‐molecule building blocks 27 difficult to target by other methodologies.
Scheme 2.7 Intermolecular remote C(sp3)–H and C–C vinylations via iminyl radicals under photoredox‐catalysis.
Source: Modified from Shen et al. [29].
Shortly after, Duan and coworkers demonstrated that a related cascade reaction could be implemented using directly styrenes [30]. In this case, a broad range of substitution pattern was tolerated.
2.3.1.2 1,5‐HAT via Amidyl and Sulfamidyl Radicals
As discussed in Section 2.2, the strong electrophilic character of amidyl and sulfamidyl radicals means that very effective 1,5‐HAT transpositions can be achieved.
A powerful example based on SET reductions can be found in the work by Wang, who reported the remote sp3 C–H allylation of amides (Scheme 2.8) [31]. In this case, the authors used the highly electron‐poor O‐aryl hydroxyamides 28 (
The ability of amidyl radicals to undergo 1,5‐HAT has also been exploited as part of a strategy, leading to remote sp3 C–H arylated products 35. Yu and coworkers demonstrated that a site‐selective Minisci‐type reaction [33] can be achieved using the electron‐poor O‐acyl hydroxy‐amides 33 as amidyl radical precursors and several N‐heteroarenes 34 (Scheme 2.9) [34]. Upon visible light irradiation, the excited dye 3CzCIIPN promoted SET reduction of 33 (in analogy to the O‐acyl oximes), thus enabling access to the corresponding nitrogen radicals 36. A 1,5‐HAT process gave the carbon radical 37, which underwent addition to an activated heteroarene to give 38. The authors suggested that under basic conditions, a proton and electron transfer took place, thus leading to the desired product 39. This reactivity displayed remarkable functional group tolerance in terms of the compatible heterocycles and was used for the modification of biologically active systems.
Scheme 2.8 Remote C(sp3)–H allyation of amides using organic photocatalyst.
Source: Modified from Wu et al. [31].
Scheme 2.9 Site‐selective remote C(sp3)–H heteroarylation of amides.
Source: Modified from Chen et al. [34].
Scheme 2.10 Visible‐light‐promoted C(sp3)–H amidation and chlorination of N‐chlorosulfonamides.
Source: Modified from Quin and Yu [35].
The generation of amidyl radicals through photoinduced SET reduction is not restricted to electrophores embedded into a N–O systems but can also be performed on N‐Cl derivatives. This was demonstrated by Yu and coworkers in the HLF‐type reactivity of N‐Cl–N‐Ts amines 40 by using a heteroleptic Ir(III) photocatalyst under white light irradiation (Scheme 2.10) [35]. In this case, after generation of a very electrophilic sulfamidyl radical, the 1,5‐HAT took place, and then the corresponding carbon radical was chlorinated, most likely, as part of a radical chain propagation. This protocol has also been used in the assembly of many pyrrolidines 41 and also in late‐stage functionalizations of some bioactive materials, demonstrating the strong functional group compatibility.
2.3.2 Oxidative Strategies
2.3.2.1 1,5‐HAT via Iminyl Radicals
Inspired by the pioneering work of Forrester [17–20], the Leonori and the Studer group took carboxylic acid‐containing oximes 42 and used them to generate functionalized imine and ketone derivatives 43–45 (Scheme 2.11) [36–38]. These processes were all based on a reductive quenching photoredox cycle and required basic conditions to trigger the SET oxidation of the carboxylate functionality (46). This event led to two β‐scissions extruding CO2 and acetone and forming the corresponding iminyl radical 47. This species then underwent 1,5‐HAT and the incipient carbon radical 48 was intercepted and diversified with several radical trapping agents (X–Y) such as N‐chlorosuccinimide (NCS; chlorination, 43), selectfluor (fluorination, 44), and Michael acceptors (Giese addition, 45). A final electron transfer between the reduced photocatalyst and the Y· intermediate, generated upon atom transfer/addition, led to an overall redox‐neutral process. This approach for remote ketone functionalization tolerated important functionalities such as protected amines, heteroaromatics, free alcohols, and ester groups among others. Interestingly, in the case of NCS, the intermediate NH imine was directly intercepted
