Asymmetric C(sp2)H Activation Wencel-Delord, Joanna; Colobert, Françoise
Chemistry : a European journal,
October 11, 2013, Volume:
19, Issue:
42
Journal Article
Peer reviewed
A “niche” topic in the past decade, the asymmetric CH bond activation has been attracting growing interest over the last few years. Particularly significant advances have been achieved in the field ...of direct, stereoselective transformations of C(sp2)H bonds. This Concept article intends to showcase different types of asymmetric C(sp2)H bond activation reactions, emphasising both the nature of the stereo‐discriminating step and the variability of valuable scaffolds that could be rapidly constructed by means of such strategies.
What is the stereodiscriminant step in C(sp2)H activation? The aim of this Concept article is to showcase and discuss the significant advances in asymmetric C(sp2)H bond transformations. Particular attention is put on the nature of the chirality inducing step and the versatility of the valuable scaffolds easily accessible from such strategies (see scheme).
The use of coordinating moieties as directing groups for the functionalization of aromatic CH bonds has become an established tool to enhance reactivity and induce regioselectivity. Nevertheless, ...with regard to the synthetic applicability of CH activation, there is a growing interest in transformations in which the directing group can be fully abandoned, thus allowing the direct functionalization of simple benzene derivatives. However, this approach requires the disclosure of new strategies to achieve reactivity and to control selectivity. In this review, recent advances in the emerging field of non‐chelate‐assisted CH activation are discussed, highlighting some of the most intriguing and inspiring examples of induction of reactivity and selectivity.
Directionless? Obtaining high levels of reactivity and selectivity is crucial for extending the scope of modern CH activation chemistry. Whereas most of these transformations rely on the help of directing groups (DGs; leading to ortho‐functionalized products and a remaining DG), the development of powerful alternative strategies is of utmost importance. Progress and trends of this evolving field are discussed.
Described is a new hydrazone‐based exo‐directing group (DG) strategy developed for the functionalization of unactivated primary β C−H bonds of aliphatic amines. Conveniently synthesized from ...protected primary amines, the hydrazone DGs are shown to site‐selectively promote the β‐acetoxylation and tosyloxylation via five‐membered exo‐palladacycles. Amines with a wide scope of skeletons and functional groups are tolerated. Moreover, the hydrazone DG can be readily removed, and a one‐pot C−H acetoxylation/DG removal protocol was also discovered.
All about the DGs: A hydrazone‐based exo‐directing group (DG) strategy is developed for the functionalization of unactivated primary β C−H bonds of aliphatic amines. The hydrazone DGs can be conveniently installed and removed, and promote β‐acetoxylation and tosyloxylation via a five‐membered exo‐palladacycle. PG=protecting group, Ts=4‐toluenesulfonyl.
A Ru‐catalyzed direct CH activation/meta‐bromination of arenes bearing pyridyl, pyrimidyl, and pyrazolyl directing groups has been developed. A series of bromo aryl pyridines and pyrimidines have ...been synthesized, and further coupling reactions have also been demonstrated for a number of representative functionalized arenes. Preliminary mechanistic studies have revealed that this reaction may proceed through radical‐mediated bromination when NBS is utilized as the bromine source. This type of transformation has opened up a new direction for the radical non‐ipso functionalization of metal with regard to future CH activation development that would allow the remote functionalization of aromatic systems.
A method for direct ruthenium‐catalyzed meta‐bromination of arenes bearing various pyridyl or pyrimidyl directing groups (DGs) is reported. This procedure is demonstrated in the concise synthesis of Vismodegib, and mechanistic studies suggest that bromination proceeds through radical intermediates.
Pd(II)-catalyzed enantioselective C(sp
3
)−H cross-coupling of free carboxylic acids with organoborons has been realized using either mono-protected amino acid (MPAA) ligands or mono-protected ...aminoethyl amine (MPAAM) ligands. A diverse range of aryl- and vinyl-boron reagents can be used as coupling partners to provide chiral carboxylic acids. This reaction provides an alternative approach to the enantioselective synthesis of cyclopropanecarboxylic acids and cyclobutanecarboxylic acids containing α-chiral tertiary and quaternary stereocenters. The utility of this reaction was further demonstrated by converting the carboxylic acid into cyclopropyl amine without loss of optical activity.
Manganese is a non‐toxic, inexpensive and earth abundant metal, so is a perfect candidate for catalysis whether as a replacement for precious metals or in the search for novel reactivity. Despite ...this, manganese catalysis has not undergone the same development of other earth‐abundant metals (particularly iron and cobalt). This review details recent synthetic methodologies using manganese catalysts, including C–H activation, late stage fluorination, hydrosilylation and cross‐coupling.
The manganese‐catalysed functionalisation of organic molecules is reviewed with regard to synthetic applications. Manganese‐catalysed C–H oxidations, halogenations, cross‐couplings and C–H activations are discussed with mechanisms details.
The use of enaminones as effective synthons for a directed C-H functionalization is reported. Proof-of-concept protocols have been developed for the Rh(III) -catalyzed synthesis of naphthalenes, ...based on the coupling of enaminones with either alkynes or α-diazo-β-ketoesters. Two inherently reactive functionalities (hydroxy and aldehyde groups) are integrated into the newly formed cyclic framework and a broad range of substituents are tolerated, rendering target products readily available for further elaboration.
A procedure for the Cp*CoIII‐catalyzed direct CH amidation of arenes with dioxazolone has been developed. This reaction proceeds under straightforward and mild conditions with a broad range of ...substrates, including anilides. A comparative study on the catalytic activity of Group 9 {Cp*MCl2}2 complexes revealed the unique efficiency of the cobalt catalyst.
Pick of the bunch: A variety of arenes, including anilides, underwent direct CH amidation with dioxazolones in the presence of a cobalt catalyst with a Cp* ligand under mild and straightforward reaction conditions (see scheme; Piv=pivaloyl). A comparative study of Group 9 Cp*MIII complexes revealed the unique ability of the cobalt catalyst to promote this transformation efficiently.
A rhodium(III)‐catalyzed carboxylic acid directed decarboxylative CH/CH cross‐coupling of carboxylic acids with thiophenes has been developed. With a slight adjustment of the reaction conditions ...based on the nature of the substrates, aryl carboxylic acids with a variety of substituents could serve as suitable coupling partners, and a broad variety of functional groups were tolerated. This method provides straightforward access to biaryl scaffolds with diverse substitution patterns, many of which have conventionally been synthesized through lengthy synthetic sequences. An illustrative example is the one‐step gram‐scale synthesis of a biologically active 3,5‐substituted 2‐arylthiophene by way of the current method.
Who was in control? A rhodium(III)‐catalyzed carboxylic acid directed decarboxylative CH/CH cross‐coupling of benzoic acids with thiophenes has been developed. This method provides straightforward access to biaryl scaffolds with diverse substitution patterns, many of which previously required lengthy synthetic sequences.
An efficient and external oxidant-free, Cp*Co(III) -catalyzed C(sp(3) )-H bond amidation of 8-methylquinoline, using oxazolone as an efficient amidating agent, is reported for the first time under ...mild conditions. The reaction is selective and tolerates a variety of functional groups. Based on previous reports and experimental results, the deprotonation pathway proceeds through an external base-assisted concerted metalation and deprotonation process.
PDF
