Carbon Dioxide-Mediated C(sp2)–H Arylation of Primary and Secondary Benzylamines

Abstract

Carbon-carbon bond formation by transition metal-catalyzed C–H activation has become an important strategy to fabricate new bonds in a rapid fashion. Despite the pharmacological importance of <i>ortho</i>-arylbenzylamines, however, effective <i>ortho</i>-C–C bond formation from C–H bond activation of free primary and secondary benzylamines using Pd<sup>II</sup> remains an outstanding challenge. Presented herein is a new strategy for constructing <i>ortho</i>-arylated primary and secondary benzylamines mediated by carbon dioxide (CO<sub>2</sub>). The use of CO<sub>2</sub> is critical to allowing this transformation to proceed under milder conditions than previously reported, and that are necessary to furnish free amine products that can be directly used or elaborated without the need for deprotection. In cases where diarylation is possible, a chelate effect is demonstrated to facilitate selective monoarylation.

Carbon Dioxide-Driven Palladium-Catalyzed C–H Activation of Amines: A Unified Approach for the Arylation of Aliphatic and Aromatic Primary and Secondary Amines

“…We considered that our strategy using CO 2 could facilitate a milder reaction that would obviate the challenges associated with the previous approaches. 39 After re-optimization of the conditions for aliphatic amines, 35 we were delighted to find that we could achieve the selective γ-C(sp 2 )-H arylation of benzylamines with a variety of aryl iodides (Scheme 5), including uncommon examples such as those containing F 3 CO-, F 2 HCO-, and even 2iodostrychnine. Again, in the absence of CO 2 , less than 10% yield of the ortho-arylated products was obtained.…”