Pd(II)-Catalyzed Direct γ-C(sp³)-H Arylation between Free β²-Amino Esters and β³-Amino Esters and Aryl Iodides Using a Catalytic Transient Directing Group

Abstract

Pd(II)-catalyzed direct γ-C(sp 3 )-H arylation coupling with free β 2 -amino esters and β 3 -amino esters using a commercially available catalytic transient directing group has been developed. This approach features high efficiency, broad substrate tolerance, easily accessible starting materials, and mild reaction conditions.

Ligand-promoted palladium-catalyzed β-methylene C–H arylation of primary aldehydes

“…This work was succeeded by many other reports that expanded the reaction and the TDG scopes. 12–14 However, this system suffers from a significant restriction that demanded resolution; only substitution of methyl C–H bonds of linear aldehydes was made possible via this approach (Scheme 1a–e). The steric limitations caused by incorporating additional groups at the β-carbon proved to compromise the formation of the palladacycle intermediate, rendering the subsequent functionalization a difficult task.…”

Transient Directing Groups in Metal−Organic Cooperative Catalysis

“…This γ-arylation could also be extended to free amino esters -however with a subsequent reesterification -(Scheme 73, c) [50] and β 2 -and β 3 -amino esters (Scheme 73, d) [135] using 2-hydroxynicotinaldehyde as the transient directing mediator, already used by Yu. Notably, acetals can be utilized instead of aldehydes as transient directing mediators, as highlighted by the Bull group which demonstrated the efficiency of phenoxyand 4-(trifluorophenoxy)-acetaldehyde methyl acetals for the γarylation of aliphatic amines in moderate yields (Scheme 73, e).…”

Transient imine directing groups for the C–H functionalisation of aldehydes, ketones and amines: an update 2018–2020

“…Liu and Wang demonstrated an effective method for the arylation of β-alanine derived amino esters using 2-hydroxynicotinaldehyde as a transient directing group (Scheme 21e). 69 Unusually, this method used a Pd/Pd co-catalytic system which was found to be most effective to promote the reaction. The use of the amino ester was key to reactivity, preventing potential competitive coordination from the substrate/product and catalyst poisoning.…”

“…Liu and Wang also demonstrated the method used previously for γ-functionalisation of β-alanines could also be used for δ-C-H arylation, using 2-hydroxynicotinaldehyde as the transient directing group (Scheme 23b). 69 This would result from the reaction going by a rare 6,6 palladacyclic intermediate.…”