(a) Synthesis of tert-butyl 3-(4-nitrophenyl)azetidine-1-carboxylate (16): 1,2-dibromoethane (0.146 mL, 1.69 mmol) was added to a vigorously stirred suspension of zinc powder (0.901 g, 13.8 mmol) in THF (3.5 mL) under nitrogen protection. The resulting suspension was heated at 80°F for 10 minutes. Subsequently, a solution of trimethylmethylsilyl chloride (0.202 mL, 1.59 mmol) in THF (1.75 mL) was added at room temperature and stirred for 4 minutes followed by the slow dropwise addition of tert-butyl 3-iodoazetidine-1-carboxylate (3.00 g, 10.6 mmol) in THF (3.5 mL), the dropwise addition process lasting 15 minutes. The reaction mixture was stirred at room temperature for 2 h, after which Pd2(dba)3 (0.155 g, 0.170 mmol) and tri-2-furanylphosphine (0.143 g, 0.615 mmol) were added, followed by a THF (18 mL) solution of 1-iodo-4-nitrobenzene (2.90 g, 11.7 mmol). The reaction mixture was heated at 55°C for 3 h. Upon completion of the reaction, the reaction was quenched with saturated aqueous sodium chloride solution (15 mL). The aqueous phase was extracted with dichloromethane (2 x 15 mL), the organic phases were combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CombiFlash Rf, 40 g SiO2 column, cyclohexane solution with 10-40% EtOAc) to afford the title compound 16 as a pale yellow oil (2.14 g, 72%).1H NMR (300 MHz, CDCl3) δ 8.24 (dd, J = 6.8, 1.9 Hz, 2H) 7.51 (d, J = 8.6 Hz, 2H), 4.41 (t, J = 8.7 Hz, 2H), 3.98 (dd, J = 8.5, 5.7 Hz, 2H), 3.89-3.81 (m, 1H), 1.49 (s, 9H).
