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Enantioselective carbon-hydrogen (C-H) activation reactions by asymmetric metallation could provide new routes for the construction of chiral molecules.sup.1,2. However, current methods are typically limited to the formation of five- or six-membered metallacycles, thereby preventing the asymmetric functionalization of C-H bonds at positions remote to existing functional groups. Here we report enantioselective remote C-H activation using a catalytic amount of a chiral norbornene as a transient mediator, which relays initial ortho-C-H activation to the meta position. This was used in the enantioselective meta-C-H arylation of benzylamines, as well as the arylation and alkylation of homobenzylamines. The enantioselectivities obtained using the chiral transient mediator are comparable across different classes of substrates containing either neutral [sigma]-donor or anionic coordinating groups. This relay strategy could provide an alternative means to remote chiral induction, one of the most challenging problems in asymmetric catalysis.sup.3,4. Remote, enantioselective C-H activation reactions can be achieved by relaying ortho-C-H activation to the meta position, using a chiral norbornene as the mediator., Author(s): Hang Shi [sup.1] , Alastair N. Herron [sup.1] , Ying Shao [sup.1] , Qian Shao [sup.1] , Jin-Quan Yu [sup.1] Author Affiliations: (1) Department of Chemistry, The Scripps Research [...]

The development of C(sp 3 )-H functionalizations of free carboxylic acids has provided a wide range of versatile C-C and C-Y (Y=heteroatom) bond-forming reactions. Additionally, C-H functionalizations have lent themselves to the one-step preparation of a number of valuable synthetic motifs that are often difficult to prepare through conventional methods. Herein, we report a β- or γ-C(sp 3 )-H carbonylation of free carboxylic acids using Mo(CO) 6 as a convenient solid CO source and enabled by a bidentate ligand, leading to convenient syntheses of cyclic anhydrides. Among these, the succinic anhydride products are versatile stepping stones for the mono-selective introduction of various functional groups at the β position of the parent acids by decarboxylative functionalizations, thus providing a divergent strategy to synthesize a myriad of carboxylic acids inaccessible by previous β-C-H activation reactions. The enantioselective carbonylation of free cyclopropanecarboxylic acids has also been achieved using a chiral bidentate thioether ligand., (© 2021 Wiley-VCH GmbH.)

The development of C-H activation reactions that use inexpensive and practical oxidants remains a significant challenge. Until our recent disclosure of the β-lactonization of free aliphatic acids, the use of peroxides in C-H activation reactions directed by weakly coordinating native functional groups was unreported. Herein, we report C(sp 3 )-H β-acetoxylation and γ-, δ-, and ε-lactonization reactions of free carboxylic acids enabled by a novel cyclopentane-based mono- N -protected β-amino acid ligand. Notably, tert -butyl hydrogen peroxide is used as the sole oxidant for these reactions. This reaction has several key advantages over other C-H activation protocols: (1) exclusive monoselectivity was observed in the presence of two α-methyl groups; (2) aliphatic carboxylic acids containing α-hydrogens are compatible with this protocol; (3) lactonization of free acids, affording γ-, δ-, or ε-lactones, has been achieved for the first time.