Remote C-H Bond Functionalizations. Группа авторов

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Scheme 2.25 meta‐C–H olefination of tertiary benzylamines and distal arene‐tethered tertiary amine derivatives.

      2.2.3.3 Phenylethylamine Derivatives

In 2015, the group of Li achieved the first meta‐C–H olefination of N‐methyl‐phenylethylamine derivatives using the 2‐cyanobenzoyl group as the CF (Scheme 2.26) [34], followed by the isolated examples of meta‐C–H olefination of tertiary phenylethylamine derivatives mentioned in Section 2.2.3.2 [33]. In presence of Pd(OAc)₂ and Ac‐Gly‐OH under nitrogen atmosphere, the reaction proceeded smoothly with a broad scope of substrate, and the directing template is structurally very simple and commercially available. Moreover, to increase the potential of application of direct C–H transformations in organic synthesis, using 2‐cyanobenzoyl group as the common original directing functionality to access regiodivergent C–H activation was also demonstrated in a sequential remote‐selective C–H olefination of 2‐fluorophenylethylamine (Scheme 2.27). Notably, the first remote‐selective C–H olefination occurs with the secondary amide 67 leaving the proximal aromatic ortho‐C

Scheme 2.26 meta‐C–H olefination of phenylethylamine derivatives.

      Source: Modified from Li et al. [34].

Scheme 2.27 Sequential remote‐selective regiodivergent C–H olefination of 2‐fluorophenylethylamine.

      2.2.3.4 N‐Heterocyclic Arene Derivatives

Due to the prevalence of N‐heterocycles in biologically important molecules, selective activation of a C

H bond of N‐heterocyclic arenes is a conceptually intriguing and synthetically important challenge. For example, to selective activation of C

H bonds at C7 of bicyclic tetrahydroquinolines, a novel template will be required since a highly strained intermediate with a tricyclic cyclophane structure will be encountered. In 2014, Yu and coworkers found the template conformation was a critical factor in controlling remote meta‐ or ortho‐selectivity, and when a fluorine substituent was introduced into the auxiliary, the conformation that favored the meta‐selectivity would be dominant in the presence of the MPAA ligand Ac‐Gly‐OH (Scheme 2.28a) [31]. Intriguingly, when the substituents in the auxiliary scaffold were switched to methyl groups, high ortho‐C–H activation at C7 of bicyclic tetrahydroquinolines was observed. With this new directing template by taking advantage of conformation control, remote meta‐C–H olefination of tetrahydroquinolines was achieved in good yield and with high levels of site selectivity (Scheme 2.28b).

Scheme 2.28 (a) Conformation promoted meta‐selective activation. (b) meta‐C–H olefination of tetrahydroquinoline derivatives.

      Source: (a) Modified from Tang et al. [31].

Subsequently, Movassaghi, Yu, and coworkers developed a novel nitrile‐based sulfonamide directing template for indolines, since previous directing template for tetrahydroquinolines was not viable presumably due to that the aryl group of indolines is more electron rich and the new skeleton requires a different template to accommodate (Scheme 2.29a) [35]. The new electronically withdrawing sulfonamide linkage is crucial for the meta‐selective C–H functionalization of electron‐rich indolines that are otherwise highly reactive toward electrophilic palladation at the electron‐rich C5‐positions. With this new template and the established reaction conditions, СКАЧАТЬ