Читать книгу Methodologies in Amine Synthesis - Группа авторов - Страница 47

The conjugate amination of α,β‐unsaturated carbonyl compounds represents a fundamental strategy to construct highly valuable β‐aminocarbonyl moieties. However, the direct addition of N‐centered radicals to electron‐deficient C=C bonds is unfavorable, at least as an intermolecular processes. To address this challenge, Meggers and coworkers realized a visible‐light‐induced enantioselective β‐amination of α,β‐unsaturated 2‐acyl imidazoles 278 with N‐aryl carbamates 279 using an iridium‐based photocatalyst in combination with a chiral‐at‐rhodium Lewis acid (Δ‐RhO), through a PCET‐enabled N–H activation with the aid of a weak phosphate base, followed by a C–N radical cross‐coupling (Scheme 3.46) [60]. The reaction mechanism is proposed in Scheme 3.46b, which begins with a PCET process between the photoexcited Ir^III* and substrate 279 with the aid of the Brønsted base, affording the carbamoyl radical 281 and the reduced Ir^II species. On the other hand, chiral catalyst Δ‐RhO binds the α,β‐unsaturated compound 278 to form the Rh‐bonded intermediate 282,which then undergoes single‐electron reduction with Ir^II to provide the Rh‐enolate radical intermediate 283 and meanwhile regenerate photocatalyst Ir^III. Subsequently, the cross‐coupling of radical intermediates 281 and 283 furnishes the C—N bond of 284. Alternative pathways via the addition of carbamate radical 281 or the corresponding anion to the C=C bonds of Rh‐coordinated intermediate 282 have been discussed and excluded on the basis of the experimental observations.

Scheme 3.45 Electro‐oxidative C–H azolation of phenol and aniline derivatives.

Source: Modified from Feng et al. [59].

Direct amination of C(sp³)—H bonds via C/N‐radical cross‐coupling pathway often employs a HAT strategy (mainly 1,5‐HAT) and occurs intramolecularly. This topic has been discussed in detail within another chapter. As a distinct example, in 2017, Lei's group reported a metal‐ and oxidant‐free electrochemical protocol for the direct intermolecular C(sp³)—N bond construction via a radical cross‐coupling pathway (Scheme 3.47) [61]. The activated C(sp³)—H bonds on benzylic or allylic sites, as well as those on the α‐positions to O, S, and N atoms (286), can be aminated with various azoles 287 using this method (288a–288f). A tentative mechanism is proposed by the authors on the basis of the mechanistic studies and literature reports, as shown in Scheme 3.47b, in which N‐radical 289 serves as both a HAT reagent to produce C‐radical 290 and as a coupling partner to react with 290 to afford C–N cross‐coupling product 288.

Scheme 3.46 Enantioselective amination via PCET followed by stereo‐controlled radical cross‐coupling.

Source: Modified from Zhou et al. [60].