Reaction Steps
To a 10° C. solution of 5 (13 mg, 0.058 mmol), 1,3-diphenylisobenzofuran (162 mg, 0.60 mmol), and MeOH (12 μL, 0.30 mmol) in DMF/1H2O (95/5 v/v, 1.0 M) was added (E)-crotonaldehyde (25 μL, 0.30 mmol). The solution was stirred at 10° C. for 24 h. The reaction mixture was then diluted with Et2O (10 mL) and washed with H2O (10 mL). The aqueous layer was extracted with Et2O (10 mL×2) and the combined organics were dried (Na2SO4), and concentrated. Purification by silica gel chromatography (7% EtOAc/hex) afforded the title compound as a yellow solid in 75% yield (76 mg, 0.22 mmol); 35:1 exo:endo; 96% ee. Product ratios were determined, after reduction to the corresponding alcohol (4 eq NaBH4, EtOH (0.1 M)), by HPLC (Chiralcel OD-H column, 3% EtOAc/hex, 1.0 mL/min) exo isomers tr=14.1 min and 15.3 min, endo isomers tr=16.5 min and 20.8. IR (CH2Cl2) 3066, 3041, 2828, 2729, 1722, 1603, 1499, 1457, 1448, 1381, 1355, 1309 cm−1; 1H NMR (500 MHZ, CDCl3) δ 9.36 (d, J=5.8 Hz, 1H, CHO), 7.73-7.78 (m, 2H, ArH), 7.43-7.57 (m, 7H, ArH), 7.35-7.40 (m, 1H, ArH), 7.16-7.26 (m, 3H, ArH), 7.04-7.08 (m, 1H, ArH), 3.08 (dq, J=6.9, 4.1 Hz, 1H, CHCH3), 2.56 (dd, J=5.8, 4.2 Hz, 1H, CHCHO), 0.96 (d, J=6.9 Hz, 3H, CH3); 13C NMR (125 MHZ) δ 201.9, 147.4, 145.0, 145.0, 136.6, 135.7, 135.5, 128.8, 128.6, 128.0, 127.4, 127.3, 127.0, 126.0, 125.5, 121.7, 118.5, 91.4, 89.2, 66.0, 43.0, 34.2, 30.3, 16.5; HRMS exact mass calcd for (C24H20O2) requires m/z 341.1541, found m/z 341.1542; [α]D=−82.4 Ĉ=1.0, CHCl3).
