Transient Ligand‐Enabled Transition Metal‐Catalyzed C−H Functionalization

Abstract

Transition metal‐catalyzed C−H bond functionalization is among the most efficient and powerful strategies in synthetic organic chemistry to derivatize otherwise inert sites of organic molecules for the construction of C−C and C−heteroatom bonds. However, additional steps are often required to install the directing groups to realize selective C−H bond functionalization of the substrates. These tedious steps run counter to the step‐economical nature of the C−H activation. In contrast, direct functionalization of the substrate by using transient ligands avoids the unnecessary steps for the pre‐functionalization of the substrates. This Minireview provides a short overview of the major progress made in this field for C−H functionalization at sp2 and sp3 carbon centers with different transient working modes, including covalent, hydrogen, and ionic bonds.

Conformationally Driven Ru(II)-Catalyzed Multiple ortho-C–H Bond Activation in Diphenylpyrazine Derivatives in Water: Where Is the Limit?

“…This is somehow reflected by the smooth formation of diarylated product 5a, while the product with two arylated ortho-positions on the same benzene ring was not detected (Scheme 3). Although we were not able to prepare suitable monocrystals of 11 for X-ray analysis, its solution structure was revealed by HRMS, and by one-and two-dimensional NMR techniques (see 3 proton of the cyclometallated group and aromatic p-cymene proton, which has a through-space interaction also with one methyl group of the isopropyl group. In the 13 C NMR spectrum, the expected number of carbons corresponding to the symmetrical structure can be seen, and the metallated carbon C 2 is observed at 194.0 ppm.…”

“…Catalytic C-H bond activation and subsequent formation of new C-C bonds, or C-heteroatom bonds, have remarkably contributed to the development of chemical transformations which enable the construction of complex molecular architectures from readily available precursors by shortening synthetic pathways and reducing waste production [1][2][3][4][5][6][7]. Heteroarylation via C-H bond activation has been largely applied to material science, for example, the synthesis of conjugated dyes [8] and polymers [9].…”

Ruthenium(II)‐Catalyzed Asymmetric Inert C−H Bond Activation Assisted by a Chiral Transient Directing Group

“…To our surprise, however, the comparatively inexpensive ruthenium catalysts are seldom seen in the literature on the asymmetric inert C À H activation, [4] despite great success having been achieved in the corresponding non-asymmetric inert CÀH activation. [5] Notably, since the pioneering work of Yu and co-workers in 2016, [6] the chiral transient directing group (TDG)assisted, [7] palladium-catalyzed asymmetric inert C À H activation has emerged as an efficient tool in organic synthesis. [8] The major characteristics of this strategy is that the chiral TDG assisting the CÀH activation and enantiocontrol can form and decompose automatically in situ.…”

“…In addition, the reaction did not proceed in the absence of acid (entry 2). Screening a series of chiral amines indicated TDG-5 was the best, furnishing the product 2 a in 21 % yield and 96 % ee (entries [3][4][5][6][7][8]. Interestingly, [Cp*RhCl 2 ] 2 gave inferior results, and [Cp*IrCl 2 ] 2 proved inactive (entries 9-10).…”

Ligand‐Controlled Direct γ‐C−H Arylation of Aldehydes

“…[6] Consequently,m uch effort has focused on the formation of five-membered palladacycle species for palladium-catalyzed C(sp 3 ) À Ha ctivation, as reported by many groups in this field. [5,[7][8][9] In contrast, reports on direct C(sp 3 ) À Hf unctionalization by asix-membered palladacycle are rare (Scheme 1A, a4, a5). [10] Mechanistically,d irect functionalization of aliphatic aldehydes on g-carbon atoms would require formation of as ixmembered palladacycle intermediate in the presence of at ransient ligand (Scheme 1C), making it an extremely challenging process.…”