Aryl Bromides and Aryl Chlorides for the Direct Arylation of Benzylic Amines Mediated by Ruthenium(II)

Abstract

The ruthenium(II)-catalyzed sp3 C–H bond arylation of benzylic amines with aryl halides is reported. In the present method, aryl iodides and, more importantly, also the cheaper aryl bromides and aryl chlorides can be applied as aryl sources. Additionally, the method does not require elaborate manipulations in a glove box and can be carried out in simple screw cap vials. Potassium pivalate proved to be beneficial for the transformation with aryl bromides or iodides as aryl source, but was not required for aryl chlorides. In the latter case, the addition of PPh3 led to high conversion. 3-Methyl and 3-phenyl pyridine were established as directing groups, and the substituent in the 3-position represents a key structural feature for high conversion. The directing group can be cleaved after the transformation, which allows access to diarylmethylamines. Mechanistic studies were carried out and critically compared to mechanistic reports of related transformations.

Mechanistic and Kinetic Studies of the Direct Alkylation of Benzylic Amines: A Formal C(sp3)–H Activation Proceeds Actually via a C(sp2)–H Activation Pathway

“…6 Initial experiments using 1-bromoheptane as the alkyl source showed promising conversion of substrate 1 of ∼20% to the alkylated product 2 (Table 1, entries 1 and 2), but significant amounts of unreacted 1 (∼40%) remained. After intensively screening reaction conditions employing the [RuCl 2 ( p -cymene)] 2 catalyst without any significant improvements (not shown), 8 it turned out that [RhCl(cod)] 2 gave better conversion (Table 1, entry 3).…”

“…4 Our group recently reported several useful methods for the C–H activation of benzylic sp 3 C–H bonds directed by 3-substituted pyridin-2-yls, including Ru(0)-catalyzed arylation employing arylboronates 5 and Ru(II)-catalyzed arylation of benzylic amines with aryl halides. 6 Herein, we report detailed mechanistic investigations into a Rh(I)-catalyzed method to alkylate benzylic amines using either alkyl bromides or alkenes. It should be noted that the alkylation of 1 using alkenes catalyzed by Ru(0) was already reported by the group of Jun in 1998; 7 however, to the best of our knowledge, there have not yet been any published reports using Rh(I) catalysis or contributions dedicated to detailed mechanistic investigations of such a transformation.…”

Exploiting the C-H bond in metal catalyzed C-C bond forming reactions

“…Ruthenium (II) catalyzed arylation of acyclic amines using aryl bromides and aryl iodides. 70,71 To use neutral conditions for a direct arylation is certainly very attractive. However, one little flaw of that protocol is that boronic acid esters are used as aryl source.…”

Regio- and chemoselective Csp3–H arylation of benzylamines by single electron transfer/hydrogen atom transfer synergistic catalysis

“…Elegant methodologies using transition metal-catalyzed C–H activation have also been disclosed, though in these cases, a directing group is required for the interaction between the transition metal and the benzylic C–H bond ( Scheme 1C ). 8 …”