Remote C-H Bond Functionalizations. Группа авторов

amino acid significantly improved the yield of the reaction and improved the selectivity as well with the optimal HFIP solvent that was crucial for the full conversion of the substrate. It was found in subsequent reports that this set of novel reaction conditions was also highly effective for many of the directing templated assisted meta‐C–H transformations. In this transformation, not only the intrinsic electronic biases of the substrate were overridden (9, 10), but also challenging steric hindrance was overcome by the template (11). Intriguingly, biaryl acid substrate that has the same length between the chelating nitrile group and the target meta‐C

H bond as hydrocinnamic acid could also undergo meta‐selective C–H olefination of the remote aryl ring (12). Finally, the directing template could be easily removed by hydrolysis under basic conditions at room temperature, leading to the meta‐olefinated hydrocinnamic acids and the recycled directing template.

Scheme 2.4 meta‐C–H olefination of hydrocinnamic acid derivatives.

In 2016, Maiti and coworkers disclosed a 2‐hydroxybenzonitrile template for mono meta‐selective olefination of hydrocinnamic acids via an ester linkage (Scheme 2.5a) [14]. Due to the less statistical availability of the coordinating nitrile group compared with the original 2,2′‐azanediyldibenzonitrile directing template, high mono‐/di‐selectivity could be obtained with this new template at lower reaction temperature using 1,2‐dichloroethane (DCE) as the major solvent and HFIP as the minor solvent. Notably, hetero‐di‐olefination product could be afforded with a second meta‐C–H olefination under similar reaction conditions using HFIP as the sole solvent (Scheme 2.5b).

Scheme 2.5 (a) 2‐hydroxybenzonitrile template assisted mono meta‐selective olefination of hydrocinnamic acids; (b) meta‐selective hetero‐di‐olefination of hydrocinnamic acids.

      Source: (a) Modified from Modak et al. [14].

Most recently, Li and coworkers developed the first example of carboxy group assisted, remote meta‐selective C(sp²)–H activation with a Pd^II‐catalyst via potential κ² coordination of the carboxyl, suppressing the ortho‐C–H activation via the κ¹ coordination (Scheme 2.6a) [15]. Unlike the previous nitrogen‐based CN‐containing or heteroarene‐containing templates, this is the first oxygen‐based carboxyl‐containing template, whose coordination geometry could be considered as a pseudo‐linear coordination along the aryl–CO₂M bond similar to the nitrile‐coordination geometry. Notably, hydrocinnamic acids could be meta‐olefinated in a remote selective fashion, leaving the C

H bond ortho to the carboxy group on the same aryl intact, although carboxy group is well‐known to be a good ortho‐directing group (Scheme 2.6b). Moreover, tuning the electronic and steric properties of the carboxy group by switching the hydrogen atom ortho to the carboxy group with a fluorine atom, the yield as well as the site selectivity could be improved to some extent (Scheme 2.6c). The possible presence of κ² coordination in assisting remote‐selective C–H activation may inspire the exploration of novel site‐selectivity of the carboxyl assisted C–H activation reactions.

Scheme 2.6 (a) Proposed remote‐selective C‐H activation via κ2 coordination of the carboxyl. (b) Remote‐selective meta‐C–H olefination of hydrocinnamic acids. (c) Improved site‐selectivity and reactivity with a modified carboxyl‐containing template.

      Source: (a) Modified from Li et al. [15].

Besides Pd‐catalysts, Rh‐catalyst could also be used for olefination of hydrocinnamic acids. In 2017, Lu, Sun, Yu, and coworkers reported the first example of Rh(III)‐catalyzed, directing template assisted remote meta‐C–H olefination of hydrocinnamic acids via a postulated 12‐membered macrocyclic intermediate (Scheme 2.7a) [16]. The directing template bearing a single nitrile group was slightly different from Yu's seminal template. Moreover, molecular oxygen could be used as the terminal oxidant for this reaction. Subsequently, meta‐C–H alkenylation of hydrocinnamic acids was also realized using alkynes, which are significantly less reactive than the polarized and reactive acrylate (Scheme 2.7b) [17]. Notably, transition metal‐catalyzed meta‐alkenylation using alkynes has not been successful with Pd catalysts in previous reports on the directing template strategy.

Scheme 2.7 (a) Rh(III)‐catalyzed directing template assisted remote meta‐C–H olefination of hydrocinnamic acids. (b) Rh(III)‐catalyzed meta‐C–H alkenylation of hydrocinnamic acids using alkynes.

      Source: (a) Modified from Xu et al. [16]; (b) Modified from Xu et al. [17].

In addition to meta‐C–H olefination, meta‐C–H arylation of hydrocinnamic acids was made possible using the directing template strategy. In 2013, Yu and coworkers reported the first example of Pd‐catalyzed cross‐coupling of meta‐C

H bonds with arylboronic esters to afford meta‐arylated hydrocinnamic acids derivatives (Scheme 2.8) [18]. A more electron‐rich nitrile‐based directing template with methoxy substitutions was found to better assist this reaction. Moreover, the privileged solvent HFIP and the MPAA ligand (Ac‐Gly‐OH) previously used for meta‐C–H olefination of hydrocinnamic acid was still crucial for the reaction. Notably, tetrabutylammonium (TBA) salt tetrabutylammonium hexafluorophosphate (TBAPF₆), which might prevent undesired agglomeration of Pd(0) species to give unreactive palladium black, dramatically improved the reaction yield. It is worth mentioning that biaryl compounds are import structural motifs that are frequently found in numerous pharmaceuticals and agrochemicals.

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