Catalytic Enantioselective Transformations Involving C–H Bond Cleavage by Transition-Metal Complexes

Abstract

The development of new methods for the direct functionalization of unactivated C-H bonds is ushering in a paradigm shift in the field of retrosynthetic analysis. In particular, the catalytic enantioselective functionalization of C-H bonds represents a highly atom- and step-economic approach toward the generation of structural complexity. However, as a result of their ubiquity and low reactivity, controlling both the chemo- and stereoselectivity of such processes constitutes a significant challenge. Herein we comprehensively review all asymmetric transition-metal-catalyzed methodologies that are believed to proceed via an inner-sphere-type mechanism, with an emphasis on the nature of stereochemistry generation. Our analysis serves to document the considerable and rapid progress within in the field, while also highlighting limitations of current methods.

A Planar‐Chiral Rhodium(III) Catalyst with a Sterically Demanding Cyclopentadienyl Ligand and Its Application in the Enantioselective Synthesis of Dihydroisoquinolones

“…[5,6] While most of the research has been done with the commercially available catalyst [(C 5 Me 5 )RhCl 2 ] 2 ,c onsiderable attention has also been paid to complexes with other cyclopentadienyl ligands to control the selectivity of various transformations. [12] Major progress has been achieved by the groups of Cramer and You, who developed as eries of cyclopentadienyl ligands with C 2 symmetry and used their rhodium complexes for asymmetric catalysis ( Figure 1). [12] Major progress has been achieved by the groups of Cramer and You, who developed as eries of cyclopentadienyl ligands with C 2 symmetry and used their rhodium complexes for asymmetric catalysis ( Figure 1).…”

“…This motivated us to propose an alternative approach to chiral rhodium catalysts that is based on the separation of racemic mixtures of complexes through crystallization of their diastereomeric adducts with naturally available amino acids. [12] Driven by our interest in rhodium-catalyzed transformations of alkynes, [23] we chose an on-classical route for the synthesis of our catalyst, namely a[2+ +2+ +1] cyclotrimerization of terminal alkynes in the coordination sphere of am etal. It is noteworthy that despite the success of planar-chiral complexes in other catalytic reactions, [22] they have apparently not been used for enantioselective CÀHa ctivation thus far.…”

Chiral Bifunctional Phosphine‐Carboxylate Ligands for Palladium(0)‐Catalyzed Enantioselective C−H Arylation

“…[1] In the context of palladium(0)-catalyzed C À H activation/C À Cc oupling reactions proceeding via the catalytic cycle depicted in Scheme 1a,t he enantiodetermining step is usually the CÀHa ctivation, which occurs by ac oncerted metalation-deprotonation [CMD,o ra mbiphilic metal ligand activation (AMLA)] mechanism. [1] In the context of palladium(0)-catalyzed C À H activation/C À Cc oupling reactions proceeding via the catalytic cycle depicted in Scheme 1a,t he enantiodetermining step is usually the CÀHa ctivation, which occurs by ac oncerted metalation-deprotonation [CMD,o ra mbiphilic metal ligand activation (AMLA)] mechanism.…”

“…As eries of phosphinecarboxylic acid preligands (L3-L7), with av ariable number (1)(2)(3)(4)(5) of methylene groups separating the carboxylic acid and the binaphthyl core,w ere prepared from (R)-Binol by adapting literature procedures from Uozumi, Hayashi, and co-workers (Scheme 2). As eries of phosphinecarboxylic acid preligands (L3-L7), with av ariable number (1)(2)(3)(4)(5) of methylene groups separating the carboxylic acid and the binaphthyl core,w ere prepared from (R)-Binol by adapting literature procedures from Uozumi, Hayashi, and co-workers (Scheme 2).…”

Synthesis of Fluorine-Containing 6-Arylpurine Derivatives <i>via</i> Cp*Co(III)-Catalyzed C–H Bond Activation

“…[1][2][3] The development of effective method for synthesizing fluorine-containing functional molecules has thus gained widespread significant attention in organic synthesis. [4][5][6][7][8][9][10][11] Direct functionalization of inert C-H bonds [12][13][14][15] is a powerful tool to realize atom- 16) and step-economical 17) synthesis, and fluorine or fluorine-containing small functional groups are successfully introduced with various catalysts and reagents. [4][5][6][7][8][9] More recently, C-H functionalization reactions accompanied by selective C-F bond cleavage of multi-fluorinated coupling partners were explored.…”