The first examples of palladium-catalyzed oxidative amination of unactivated alkyl olefins have been identified. To be successful, these reactions must be conducted under cocatalyst-free conditions that involve direct dioxygen-coupled turnover of the palladium catalyst. The oxidative amination products of norbornene and other cyclic alkenes implicate a cis-aminopalladation mechanism.
Gas chromatography was performed with a Shimadzu GC-17A gas chromatograph equipped with a 15 m RTX-5 capillary column (Restek). Flash chromatography was performed on silica gel 60 (particle size 0.040-0.063mm, 230-400 mesh ASTM, purchased from Sorbent Technology) with hexanes/diethylether or methylene chloride.
General Procedure for Catalyst Screening.In a disposable culture tube, phthalimide (0.5 mmol, 73.6 mg), catalyst (0.025 mmol), additive (0.025 mmol) and PhCN (0.667 mL) were combined. The reaction tubes were placed into a custom 48-well parallel reactor mounted on a Large Capacity Mixer (Glas-Col) and the headspace was purged with molecular oxygen for ca. 15 min. After warming to 60° C, 1-octene (3.0 mmol, 0.47 mL) was added to each tube to initiate the reactions. The reactions were vortexed for 24 h under 1 atm molecular oxygen. Upon cooling, 1,3,5-trimethoxybenzene (0.056 mmol, 9.4 mg) internal standard was added to each reaction mixture. Terminal enamide product yield was evaluated by 1 H NMR spectroscopy relative to the internal standard. Yield of additional amination products was established by gas chromatography. Determination of percent conversion phthalimide was hindered by poor solubility and low detector (FID) response.
General Procedure for the Palladium-Catalyzed Oxidative Amination of Aryl and Alkyl Olefins.A typical procedure is given for the reaction of 1-octene with phthalimide, Pd(OAc) 2 (0.025 mmol, 5.6 mg) and phthalimide (0.50 mmol, 73.6 mg) were suspended in PhCN (0.667 mL) in 13x100 mm disposable culture tubes. The reaction tubes were placed into a custom 48-well parallel reactor mounted on a Large Capacity Mixer (Glas-Col) and the headspace was purged with molecular oxygen for ca. 15 min. After warming to 60 °C, octene (3.0 mmol, 0.47 mL) was added to each tube to initiate the reactions. The reactions were carried out for 24 h under an oxygen atmosphere (1 atm). For product purification, four individual reactions were combined and adsorbed onto silica gel. The product was isolated by eluting with ether/hexanes to give a 87 % yield S2 (447 mg) of 2-(1-hexylvinyl)-isoindol-1,3-dione. Performing this reaction in a 25 mL round-bottom flask equipped with a magnetic stir bar under an oxygen balloon resulted in comparable yield, 76 % yield (391 mg).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.