Palladium-catalyzed C-H functionalization using guanidine as a directing group: ortho arylation and olefination of arylguanidines

Abstract

Palladium-catalyzed C-H functionalization using guanidine as the directing group was achieved under mild reaction conditions. Various guanidine derivatives were produced in moderate to good yields by using simple unactivated arenes or ethyl acrylate as the source of arylation or olefination, respectively.

Scheme 1

^a Reaction conditions: guanidine carbonate salts (0.5 mmol, 1.0 equiv), Pd(OAc)₂ (10 mol %), arene (1 mL), TFA (5 mmol, 10 equiv), K₂S₂O₈(1.5 mmol, 1.0 equiv), 65 °C, 48 h. ^b Reaction was performed at 80 °C for 64 h. ^c The ratio of the regioisomers was detemined by ¹H NMR, products were isolated as their HCl saits, isolated yield.

Scheme 2

The Ortho-Arylation of Protected Phenylguanidine. The Scope of The Orytho-Arylation Reaction.^{a, c}

Scheme 3

The Ortho-Olefination of Phenylguanidines with Ethyl Acrlate.^{a a} Reaction conditions: guanidine carbonate salts (0.5 mmol, 1.0 equiv), ethyl acrylate (0.75 mmol, 1.5 equiv), Pd(OAc)₂ (10 mol %), BQ (0.75 mmol, 1.5 equiv), HOAc (1.5 mL), 65 °C, 5 h, products were isolated as their HCl saits, isolated yield. ^b 2.5 equiv of ethyl acrylate was used, reaction was performed at 80 °C for 17 h ^c Reaction was performed at 80 °C for 24 h.

Scheme 4

Plausible Catalyic Mechanisms for the C-H Bond Activation.