Description
(R)-2-Phenylpiperidine is an alkene that has been used in the desymmetrization of secondary amides to produce enantiopure products. It has been shown to be stereoselective. It could prepared from δ-Amino β-keto esters 3. The kinetic resolution of this compound is due to the formation of an enamine, which undergoes a 1,4-addition reaction with an aldoxime or piperidone.
Synthesis
In a 10 mL one-necked round-bottomed flask equipped with a magnetic stir bar, rubber septum, and argon balloon was placed 0.033 g (0.19 mmol, 1 equiv.) of (R)-(+)-6-Phenylpiperidin-2-one and THF (1.2 mL). Lithium aluminum hydride (0.95 mL, 1.0 M solution in THF, 0.95 mmol) was added slowly via syringe and the reaction mixture was stirred at rt for 8 h. The solution was cooled to 0 °C, sat. Na2SO4 (0.17 mL) was added, stirred for 0.5 h at rt and the reaction mixture was filtered through Celite. The organic phases were concentrated and flash chromatography (7% MeOH/CH2Cl2) gave 0.025 g (82%) of (R)-2-phenylpiperidine as volatile oil.
