Magnesium → (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate

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Reaction Steps

Magnesium (0.110 g, 4.58 mmol) turnings were stirred in a round bottom flask under nitrogen for 30 min. to cause scratching of the surface of the magnesium. 10 mL of THF was added to the magnesium turnings and stirred for an additional 30 min. 4′-bromo-2-vinylbiphenyl (Intermediate 1, 1.13 g, 4.36 mmol) in THF (30 mL), was added dropwise at reflux with vigorous stirring. The Grignard solution (40 mL) was added to a solution of (S)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-oxopyrrolidine-1,2-dicarboxylate (Intermediate 2, 1.0 g, 3.53 mmol) in toluene (30 mL) at 0° C. and stirred for 1 hr and then quenched with a saturated NH4Cl solution. The aqueous layer was extracted with DCM. The combined organics were washed with brine and dried over MgSO4, filtered and evaporated to give crude material. The crude material was purified by flash chromatography on the Biotage (20-33% EtOAc:Hex) to give (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(2′-vinylbiphenyl-4-yl)pyrrolidine-1,2-dicarboxylate (0.5 g, 30% yield) as a yellow oil. LCMS: rt=1.92 min. [M+Na]+=490; Phenomenex-Luna C-18 (5μ) (3.0×50 mm); Solvent A=10% acetonitrile—90% water—0.1% TFA, Solvent B=90% acetonitrile—10% water—0.1% TFA; gradient 0% to 100% solvent B over 2 min. and then hold for 1 min.; 4 mL/min; inj. vol.=5 uL; wavelength=220. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 0.06 (s, 9H) 0.88-1.14 (m, 2H) 2.38-2.50 (m, 1H) 2.74 (dd, J=13.58, 10.22 Hz, 1H) 3.89 (d, J=11.60 Hz, 2H) 3.76-3.84 (m, 1H) 3.86 (s, 3H) 4.00 (dd, 1H) 4.23 (s, 1H) 4.24-4.28 (m, 1H) 4.55-4.66 (m, 1H) 5.20 (dd, J=10.9, 1.22 Hz, 1H) 5.71 (dd, J=17.55, 1.07 Hz, 1H) 6.70 (dd, J=17.40, 10.99 Hz, 1H) 7.28 (dd, 1H) 7.34 (dd, J=7.17, 1.68 Hz, 1H) 7.37 (d, J=8.55 Hz, 2H) 7.54 (d, J=8.24 Hz, 2H) 7.65 (d, J=7.32 Hz, 1H).

Provenance & Evidence