Reaction Steps
To a suspension of N-propyl-2-bromo pyridinium triflate (285 mg, 0.824 mmol) and 4-pyrrolidinopyridine (183 mg, 1.24 mmol) in CH2Cl2 (11.5 mL) was added Hünig's base (72 μL, 0.41 mmol) at 0° C. After stirring for 10 min, a solution of keto-acid 60 (200 mg, 0.412 mmol) in CH2Cl2 (5 mL) was added via syringe pump over 1 h at 0° C. The resulting suspension was stirred for 3 h at 0° C., at which point the volatiles were removed up to one-third under reduced pressure. The crude reaction mixture was diluted with Et2O (100 mL) and washed with aqueous NH4Cl solution and brine (each 30 mL). The organic layer were dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (1:10 EtOAc/hexanes) to give a mixture of two beta-lactones (60 mg, 31%, dr 1:1.6) as a colorless oil. (±)-61 (major): Rf=0.56 (20% EtOAc/hexanes); IR (neat) 1829,1701 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.22 (d, J=8.5 Hz, 2H), 6.84 (d, J=9.0 Hz, 2H), 4.76 (d, J=15.5 Hz, 1H), 4.28 (d, J=15.0 Hz, 1H), 3.80 (s, 3H), 2.75 (t, J=7.0 Hz, 1H), 1.65-2.03 (m, 15H), 1.39 (s, 3H), 0.85-1.34 (m, 13H); 13C NMR (75 MHz, CDCl3) δ 175.0, 169.2, 159.3, 129.6, 129.4, 114.2, 86.8, 76.4, 55.4, 44.4, 42.2, 38.1, 35.0, 33.6, 33.5 (2), 33.3, 33.2, 31.7, 30.8, 26.7, 26.6, 26.3 (3), 13.0; LRMS (ESI) Calcd. for C29H41NO4 [M+H] 468, found 468. (±)-61b (minor): Rf=0.63 (20% EtOAc/hexanes); IR (neat) 1829, 1702 cm−1; 1H NMR (500 MHz, CDCl3) δ 7.18 (d, J=8.5 Hz, 2H), 6.83 (d, J=8.5 Hz, 2H), 4.87 (d, J=15.5 Hz, 1H), 4.17 (d, J=15.5 Hz, 1H), 3.79 (s, 3H), 2.87 (dd, J=3.5, 11.0 Hz, 1H), 2.06 (br d, J=12.5 Hz, 1H), 1.46-1.87 (m, 12H), 1.14-1.42 (m, 12H), 0.79-1.10 (m, 4H); 13C NMR (125 MHz, CDCl3) δ 174.3, 169.3, 159.0, 129.6, 128.9, 114.0, 87.2, 76.8, 55.2, 44.2, 43.8, 37.9, 37.4, 34.7, 34.5, 33.2, 33.0, 32.1, 30.4, 27.3, 26.5, 26.4, 26.2, 25.8, 12.3.
