Development of Chiral Ligands for the Transition‐Metal‐Catalyzed Enantioselective Silylation and Borylation of C−H Bonds

Abstract

Enantioselective reactions that install functional groups at the positions of unactivated C−H bonds can be envisioned to produce intermediates for the synthesis of the active ingredients in pharmaceuticals and agrochemicals directly from simple feedstocks. Among these C−H bond functionalization reactions, those that form carbon–silicon (C−Si) and carbon–boron (C−B) bonds have been pursued because the products of these reactions can be converted to those containing a wide range of functional groups and because compounds containing silicon and boron possess unique properties that can be valuable for medicinal and materials chemistry. Although the silylation and borylation of C−H bonds have undergone extensive development during the past two decades, enantioselective versions of these reactions were not known until a few years ago. In this Minireview, we present the rapid development of enantioselective silylation and borylation of C−H bonds, with an emphasis on the design and development of the types of chiral ligands needed to achieve these reactions and an intention to inspire an expansion of these types of transformations.

Metal-catalysed C–H bond activation and borylation

“…However, the groups of Sawamura, Yu, Hartwig, Xu, and others have developed many aliphatic borylations including enantioselective versions. 84 Thus, we also intend to highlight these discoveries in a separate section. Collectively, this review article aims to discuss the recent developments for the transition metal-catalysed directed proximal ortho selective borylation, distal meta and para selective borylation and directed aliphatic C-H borylation including its enantioselective variant.…”

Atroposelective Synthesis of C–C Axially Chiral Compounds via Mono- and Dinuclear Vanadium Catalysis

“…Such chiral biaryls have been attractive targets in asymmetric synthesis . In addition, atropisomerism of chiral biaryls with rotationally constrained σ-bonds is found in numerous synthetic organic molecules used as chiral ligands and catalysts − as well as in natural products that exhibit pharmaceutical utility (Figure ). …”

Asymmetric Remote meta-C–H Activation Controlled by a Chiral Ligand

“…In the past decades, the major advances in asymmetric C–H activation of arenes have relied on the use of chiral ligands that bind to transition-metals such as Pd, Rh, and Ir catalysts, , forming generally five- or six-membered chiral metallacycles which can be diversely functionalized afterward . However, this strategy is thus far unexplored for asymmetric functionalization of a C–H bond distal to existing functional groups because it seems that the stereocenter of the ligand is too far from the prochiral center of the substrate. − Therefore, the development of a strategy for remote chiral induction has been a daunting challenge because this process requires the simultaneous control of stereoselectivity and site-selectivity during the transformation of a remote chemical bond.…”

“…In the past decades, the major advances in asymmetric C–H activation of arenes have relied on the use of chiral ligands that bind to transition-metals such as Pd, Rh, and Ir catalysts, , forming generally five- or six-membered chiral metallacycles which can be diversely functionalized afterward . However, this strategy is thus far unexplored for asymmetric functionalization of a C–H bond distal to existing functional groups because it seems that the stereocenter of the ligand is too far from the prochiral center of the substrate. − Therefore, the development of a strategy for remote chiral induction has been a daunting challenge because this process requires the simultaneous control of stereoselectivity and site-selectivity during the transformation of a remote chemical bond. To date, only two reports were disclosed for asymmetric remote meta -C–H activation of arenes, representing two distinct strategies. , The first breakthrough in asymmetric remote C–H activation was achieved by the Yu group in their asymmetric remote meta -C–H arylation and alkylation of benzylamines and homobenzylamines using the impressive relay strategy with a chiral transient mediator for the chiral induction of the initial cleavage of an ortho -C–H bond (Scheme a) .…”