Synthesis of diarylmethylamines via palladium-catalyzed regioselective arylation of 1,1,3-triaryl-2-azaallyl anions

Abstract

Diarylmethylamines are of great interest due to their prevalence in pharmaceutical chemistry. As a result, new methods for their synthesis are in demand. Herein, we report a versatile protocol for the synthesis of diarylmethylamine derivatives involving palladium-catalyzed arylation of in situ generated 2-azaallyl anion intermediates. The 2-azaallyl anions are generated by reversible deprotonation of readily available aldimine and ketimine precursors. Importantly, the arylated aldimine and ketimine products do not undergo isomerization under the reaction conditions. Scale-up of the arylation and hydrolysis of the resulting products to furnish diarylmethylamines were also successfully performed.

Room-temperature palladium-catalyzed direct 2-arylation of benzoxazoles with aryl and heteroaryl bromides

“…Substrates reported to date include chromium-activated benzylic amines, 7 diarylmethanes, 8 allylarenes, 9 amides, 10 sulfones, 11 sulfoxides, 12 imines, 13 phosphine oxides 14 and benzylic phosphonates. 15 We have found that van Leeuwen’s NiXantphos 16 (See Scheme 1 for structure) enables a number of these transformations, whereas other ligands are significantly less effective or fail to provide even trace products.…”

“…15 We have found that van Leeuwen’s NiXantphos 16 (See Scheme 1 for structure) enables a number of these transformations, whereas other ligands are significantly less effective or fail to provide even trace products. 8, 12a, 13 The high reactivity of the NiXantphos-based palladium catalysts may be due to the deprotonation of the ligand N–H under basic reaction conditions. 8a Based on these studies, we decided to examine DCCP of sp 2 C–H bonds.…”

Reversed‐Polarity Synthesis of Diaryl Ketones through Palladium‐Catalyzed Direct Arylation of 2‐Aryl‐1,3‐dithianes

“…We have found that different phosphine ligands are required (Figure 1, ligands L1–L5 ) for the diverse substrate classes and bases we have employed. This method has proven successful for the direct C–H arylation of diarylmethanes ( L1 ), [19] benzylic ketimines ( L1 ), [20] benzyl thioethers, [21] benzylic phosphine oxides ( L2 ), [22] methyl sulfoxides and sulfones ( L3 ), [23] amides ( L3 ), [24] benzylic phosphonates ( L4 ), [25] and allyl benzenes ( L5 ). [26] …”

Palladium‐Catalyzed C−H Arylation of α,β‐Unsaturated Imines: Catalyst‐Controlled Synthesis of Enamine and Allylic Amine Derivatives

“…A slight increase in AY was observed at 0.05 m (75 % assay yield; Table , entry 4). Buchwald precatalysts, facilitate catalyst generation, often lead to increased activity, and allow a lower ligand loading. Therefore, we employed Buchwald‐type precatalysts 6 and 7 (with L=NiXantphos; Table , entries 5 and 6).…”