N-Boc-pyrrolidine (20 g, 117 mmol, 1 eq.) and anhydrous THF (60 mL) were added to a pre-flame-dried round-bottomed flask equipped with a magnetic stirrer under nitrogen protection. The resulting clarified colorless solution was cooled to -78 °C, followed by the slow addition of s-BuLi solution (100 mL of 1.4 M cyclohexane solution, 140 mmol) over 30 min. The light orange solution was kept stirred at -78 °C for 3 h. B(OMe)3 (39 mL, 350 mmol) was then added. The cooling bath was removed and the clear colorless solution was allowed to warm slowly to 0 °C. Upon reaching 0 °C, the reaction was quenched with a small amount of water (~2 mL) and allowed to gradually warm to room temperature, followed by extraction with 2N NaOH (250 mL) and backwashing with EtOAc (150 mL). The aqueous phase was acidified to pH 3 with 2N HCl and extracted with EtOAc (3 x 120 mL). The organic phases were combined, dried over Na2SO4, and concentrated to give free boric acid (22.08 g, 103 mmol) as a viscous white solid in 88% yield. Without further purification, boric acid was dissolved in tert-butyl methyl ether (150 mL) and (+)-pyridinediol (17.5 g, 103 mmol) was added with continuous stirring at room temperature. after 18 h, the ether was removed by evaporation, and (+)-diethanolboronate was purified by column chromatography (silica gel, 1:3 hexanes/EtOAc) to give a clarified thick oily substance (26.84 g 76.8 mmol, 76% yield, Rf=0.6, observed by 12 and/or PMA staining using a 2:1 hexane/ethyl acetate eluent). The oil was dissolved in anhydrous ether, cooled to 0 °C in an ice bath and passed through dry HCl gas with continuous stirring for 10 min to remove the Boc protecting groups.After 2 h, a white precipitate was formed in the flask, and the ether and excess HCl were removed in vacuo to give the racemic HCl salt as a white solid. The HCl salt was dissolved in a minimal amount of dichloromethane (250 mL), gently heated to promote dissolution, followed by continuous stirring for 8 h to form a fluffy white precipitate (collected by vacuum filtration). After filtration and drying, the precipitate was dissolved in a very small amount of 2-propanol (about 200 mL) and gently heated until homogeneous. The alcohol solution was stirred overnight and the resulting white precipitate was collected by vacuum filtration to give isomerically pure 1 as a white solid (7.0 g, 27 mmol, 23% yield).1H NMR (400 MHz, D2O) δ 4.28 (d, J=8.0 Hz, 1H), 3.06 (m, 3H), 2.18 (m, 1H), 1.96 (m, 2H), 1.96 (m, 2H) 1.78 (m, 3H), 1.62 (m, 2H), 1.21 (s, 3H), 1.05 (m, 5H), 0.84 (d, J=12Hz, 2H), 0.71 (s, 2H), 0.62 (s, 3H).
