Removable Directing Groups in Organic Synthesis and Catalysis

Abstract

Directing groups have been widely used in recent years to achieve control over all aspects of reaction selectivity in a wide range of transformations involving transition-metal catalysis and organometallic reagents. In cases when the existing functional group within a substrate is unsuited to achieve efficient intramolecular delivery of a reagent or catalyst, the specific introduction of an appropriately designed removable reagent-directing group can be a solution to this problem. In this Review we give an overview of the state of the art in this area, including the stoichiometric and catalytic use of directing groups.

Site-selective C–H arylation of primary aliphatic amines enabled by a catalytic transient directing group

“…Pioneering studies in this area were conducted by Jun's group, who reported the rhodium-catalyzed functionalization of aldehyde C−H bonds with 2-aminopyridine as an external directing group 33 . In addition, selective C(sp 2 )−H functionalizations of phenols or alcohols have been realized with catalytic amount of phosphinite ligands via reversible transesterification 34,35 .…”

A decarboxylative approach for regioselective hydroarylation of alkynes

“…Since these pioneering studies, chelation-assisted alkyne hydroarylation has been explored with various transition-metal catalysts and a wide range of heteroatom-based directing groups 4,6,[17][18][19][20] . However, removal of these ortho-directing groups from the hydroarylation products requires additional chemical transformations and is not always achievable [21][22][23] . Thus, access to ortho-substituted alkenylarenes by alkyne hydroarylation is limited by the nature of the ortho-directing groups, and access to meta-or para-substituted alkenylarenes has not been achieved selectively by existing methods for alkyne hydroarylation 24,25 .…”

Ketone-Based Transition-Metal-Catalyzed Carbon–Carbon and Carbon– Hydrogen Bond Activation: Exploratory Studies

“…Meanwhile, if we incorporated a proper directing group (DG) in the amine agent, metalation would be directed to the α-car- bon-hydrogen bonds upon enamine formation. 21 Subsequent olefin insertion-reductive elimination and enamine hydrolysis would lead to the desired α-alkylation product. As documented in organocatalysis, enamine formation and hydrolysis can exist in an equilibrium, but the lesshindered ketone (starting material) forms the enamine faster than the hindered ketone (product).…”