Reaction Steps
The title compound is synthesized analogously to 4b except for the following changes: 1) 2.5 mol % aminophenol 2g (instead of 3 mol % 2g) 2) 1.5 equiv. MeOH (instead of 2.5 equiv.). 3) Reaction time is six h. 4) After NaIO4 workup (see representative procedure above), the unpurified mixture is treated for 12 h while allowing it to stir with ˜1 g basic aluminum oxide in 4 mL dichloromethane:diethyl ether (1:1) to hydrolyze unreacted 3j, after which the aluminum oxide is filtered off and washed with dichloromethane and ethyl acetate (20 mL). The product is purified as described for 4b, affording 4j (44.2 mg, 0.0931 mmol, 93% yield) as a white solid. M.p.=83-84° C. IR (neat): 3154 (w, br), 3071 (w), 2955 (m), 2930 (m), 2870 (m), 1614 (m), 1519 (m), 1455 (m), 1436 (m), 1368 (w), 1283 (w), 1181 (s), 1107 (s), 1066 (m), 925 (m), 900 (m), 752 (w), 722 (s), 693 (s), 553 (s), 521 (s) cm−1; 1H NMR (400 MHz, CDCl3): δ 7.89-7.79 (4H, m), 7.49-7.32 (6H, m), 7.03 (2H, d, J=8.8 Hz), 6.54 (2H, d, J=8.8 Hz), 5.63 (1H, app ddt, J=17.2, 10.0, 7.2 Hz), 5.10-4.99 (2H, m), 4.26-4.19 (1H, m), 3.23 (4H, app dd, J=7.8, 7.2 Hz), 3.26-3.21 (1H, m, overlapping with the dd at 3.23), 2.75-2.58 (2H, m), 1.59-1.52 (4H, m), 1.40-1.30 (4H, app sextet, J=7.6 Hz), 0.96 (6H, t, J=7.6 Hz); 13C NMR (100 MHz, CDCl3): δ 147.3, 134.6, 133.6 (d, J=127.0 Hz), 132.6 (d, J=9.5 Hz), 132.4 (d, J=130.0 Hz), 131.9 (d, J=9.3 Hz), 131.7 (d, J=2.7 Hz), 131.6 (d, J=2.7 Hz), 129.2 (d, J=6.3 Hz), 128.4 (d, J=12.3 Hz), 128.3 (d, J=12.4 Hz), 127.6, 118.1, 111.5, 54.3, 50.9, 43.5 (d, J=3.7 Hz), 29.5, 20.4, 14.1; HRMS Calcd for C30H40N2OP [M+H]+: 475.28782. Found: 475.28783. [α]20D=+61.6 (c=1.33, CHCl3) for a 92:8 er sample. The enantiomeric purity of this compound was determined by HPLC analysis in comparison with authentic racemic material (Chiracel OD-H, 92:8 hexanes:i-PrOH, 0.5 mL/min, 220 nm): tR of 4j: 12 min (major) and 14 min (minor).
