Diastereoselective Substrate-Controlled Transition-Metal-Catalyzed C–H Activation: An Old Solution to a Modern Synthetic Challenge

Abstract

The synthesis of chiral compounds by means of asymmetric C-H activation is an appealing modern strategy for the straightforward conversion of simple and nonfunctionalized substrates into high-valueadded stereogenic molecules. For several years, considerable attention has been focused on the design of enantioselective transformations involving the use of chiral ligands as sources of chirality. In addition, a complementary strategy based on direct functionalization of substrates bearing a chiral element has recently demonstrated its potential. Such diastereoselective transformations can be achieved by incorporating a chiral auxiliary into a directing group (DG). Alternatively, direct functionalization of chiral-pool molecules, such as α-amino acids, provides a valuable synthetic route to novel non-natural amino acid derivatives. The aim of this account is to highlight major achievements in diastereoselective C-H activation. Particular attention will be paid to the contributions of our group in this emerging field.

Pd(II)-Catalyzed Bidentate Directing Group-Aided Chemoselective Acetoxylation of Remote ε-C(sp2)–H Bonds in Heteroaryl–Aryl-Based Biaryl Systems

“…Transition metal-catalyzed sp 2 /sp 3 C–H activation/functionalization is one of the remarkable synthetic transformations in organic synthesis. − While the directing group-free C–H activation/functionalization is well documented, the directing group-aided C–H activation/functionalization has become a powerful synthetic strategy for accomplishing the site-selectivity. − Especially, the use of the bidentate directing groups (BDGs) has offered a new zeal for achieving the site-selective C–H functionalization (e.g., arylation, alkylation, and acetoxylation) of organic molecules. − The 8-aminoquinoline (8AQ)-type BDGs have preferentially assisted the functionalization of sp 2 /sp 3 β-C–H bonds of carboxylic acid substrates. − The picolinamide (PA)-type BDGs have assisted the functionalization of sp 2 /sp 3 γ- and δ-C–H bonds of amine systems. − The BDG-aided functionalization of sp 2 /sp 3 β- and γ-C–H bonds of appropriate carboxamide systems was well documented, − and there also have been some outstanding efforts on the BDG-aided functionalization of remote sp 2 /sp 3 δ- and ε-C–H bonds of appropriate carboxamide systems. ,− In particular, to the best of our knowledge, there exist only rare reports dealing on the BDG-aided functionalization of remote sp 2 /sp 3 ε-C–H bonds …”

Enantioselective C−H Activation with Earth‐Abundant 3d Transition Metals

“…It is noteworthy that the enantioselective CÀHf unctionalization of ferrocene derivatives remains challenging with 3d metal catalysts,a ss imilar moderate enantioselectivities have been obtained by Shi et al as well (Scheme 22). [59] In contrast, the use of achiral oxazoline as the directing group [72] allowed for the iron-catalyzed arylation ferrocene derivatives 88 to provide the planar-chiral products in > 99 %d iastereoselectivity but moderate yield. [71] Employing the same class of substrates,acopper-catalyzed diastereoselective thiolation of ferrocenamides was later disclosed by Yu et al [73] In contrast, Ackermannsg roup established ah ighly enantioselective iron-catalyzed C À Ha ctivation of (aza)indoles [74] (Scheme 27).…”

Challenging Atroposelective C–H Arylation

“…Targeting elaboration of unprecedented chiral scaffolds, Colobert and Wencel-Delord in 2018 were interested in the conception of optically pure molecules containing two contiguous atropisomeric axes. 15 They envisaged that such molecules might be obtained by combining diastereoselective C-H functionalization 16 of biaryls and stereoselective C-H arylation. Such triaryl scaffolds should exhibit a unique tridimensional structure, thus becoming an appealing platform to construct unprecedented chiral ligands.…”