Methodologies in Amine Synthesis. Группа авторов

an aryl substituent on the oxime. However, the site of 1,5‐HAT could be embedded into a further cyclic system, thus leading to interesting bicyclic structures.

Scheme 2.4 Photochemical intramolecular C(sp³)–H imination of tertiary aliphatic amines containing β‐O‐aryl oximes.

      Source: Modified from Li et al. [25].

More recently, Wu and coworkers have demonstrated that similar O‐aryl oximes 16 can also undergo EDA complex formation with 1,4‐diazabicyclo[2.2.2]octane (DABCO)·(SO₂)₂17 and that this can be used for iminyl radical generation upon visible light irradiation (Scheme 2.5) [26]. This step was followed by a 1,5‐HAT process, and the resulting carbon radical was able to intercept SO₂ en route to products 18. In this way, a rare example of amino‐sulfonylation of unactivated sp³ C—H bonds was achieved, leading to the assembly of biologically relevant 1,2‐thiazine dioxides.

The ability of iminyl radicals to undergo 1,5‐HAT has been recently employed for the conversion of activated acyclic O‐acyl oximes 19 into a variety of cyclic ketones 20 (Scheme 2.6). In this work, Nevado and coworkers described a redox‐neutral process, where the SET reduction of radical precursor 19 was performed by a visible‐light‐excited Ir(III) photocatalyst [27]. In this case, the authors used O‐acyl oximes that have a reduction potential accessible by many photoexcited catalysts [28]. This SET led to the corresponding iminyl radical 21 that underwent selective 1,5‐HAT. The distal carbon radical 22 was exploited in an intramolecular cyclization onto the (hetero)aromatic substituent. Oxidation of intermediate 23 by the Ir(IV) catalyst gave the imine 24, which, upon hydrolysis, delivered a variety of fused bicyclic ketones in high yields. The six‐membered ring radical cyclization enabled excellent control of relative stereochemistry when substituents were present.

Scheme 2.5 Photoinduced aminosulfonylation of C(sp³)—H bonds with sulfur dioxide.

      Source: Modified from Li et al. [26].

Scheme 2.6 Redox neutral remote functionalization of C(sp³)—H bonds via iminyl radicals.

      Source: Modified from Shu and Nevado [27].

The direct installation of vinyl groups onto unactivated sp³ C—H bonds is a transformation with powerful applications as the olefin functionality can then be elaborated in a number of different ways. An interesting solution to this challenge has been provided by Yu and coworkers 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 ( = −0.9 V vs. saturated calomel electrode [SCE]) that were previously identified as powerful electrophores for SET by the photoexcited state of the organic dye eosin Y (* = −1.1 V vs. SCE). This event led to a fragmentation across the weak N—O bond, thus delivering the key amidyl radical 29. A very facile 1,5‐HAT process was used to generate the distal carbon radical 30, which underwent allylation by reaction with a variety of sulfone reagents (e.g. 31). This step provided the product 32 with concomitant release of PhSO₂^·. The authors proposed a redox‐neutral photoredox process, whereby N,N‐diisopropylethylamine (DIPEA) closed the cycle by SET with the oxidized eosin Y. However, as quantum yield determination was not performed, a potential radical chain mechanism cannot be ruled out [32]. This reaction enabled the modification of secondary and tertiary centers and also displayed broad functional group compatibility.

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.