GENERAL METHODS: (S)- or (R)-Fmoc-proline (4.58 g, 13.6 mmol) was dissolved in anhydrous THF (125 mL) in a round-bottomed flask with a magnetic stirrer and protected by nitrogen. The reaction solution was cooled to 0 °C, followed by slow addition of NaBH4 (0.82 g, 21.7 mmol). After the reaction mixture was stirred at 0 °C for 60 min, boron trifluoride diethyl ether compound (3.4 mL, 3.85 g, 27.1 mmol) was added dropwise and stirring was continued for 18 h at 0 °C. The reaction progress was monitored by TLC (CH2Cl2/EtOAc 70:30). Upon completion of the reaction, water (30 mL) was added at 0 °C and the mixture was stirred for 30 min. Subsequently, THF was removed by vacuum evaporation and the remaining aqueous layer was extracted with EtOAc (3 x 100 mL). The organic phases were combined, washed with saturated saline, dried over anhydrous Na2SO4 and filtered. The solvent was concentrated under reduced pressure and the crude product was purified by fast chromatography using a gradient of CH2Cl2:EtOAc (95:5→85:15) as eluent. Finally, the product was precipitated with cold hexane to give (R)-N-Fmoc-pyrrolidine-2-methanol in white powder form, stored at -15 °C.
