Reaction Steps
A flask with stir bar and nitrogen line was charged with rac-(7aR,11aS)-11a-(pyridin-2-ylmethyl)-3-((E)-styryl)-5,6,7,7a,8,10,11,11a-octahydro spiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolane] (145, R2=Pyridin-2-ylmethyl) (5.9 g, 13.04 mmol), 1,4-dioxane (150 mL), water (50.0 mL), 2,6-dimethylpyridine (3.04 mL, 26.1 mmol) and osmium(VIII) oxide (2.5 wt % in tert-butanol) (4.91 mL, 0.391 mmol). Sodium periodate (11.15 g, 52.1 mmol) was added and the mixture was stirred at rt for about 15 h. The mixture was diluted with water (200 mL) and EtOAc (50 mL). The layers were separated then the aqueous layer was extracted four times with EtOAc (50 mL). The combined organics were washed twice with brine (30 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The material was triturated with EtOAc and the solids collected by filtration and dried to yield rac-(7aR,11 aR)-11a-(pyridin-2-ylmethyl)-5,6,7,7a,8,10,11,11a-octahydrospiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolane]-3-carbaldehyde (146, R2=Pyridin-2-ylmethyl) (3.89 g, 79%); LC/MS, method 3, Rt=2.00 min, MS m/z 379 (M+H)+. 1H NMR (400 MHz, DMSO) δ 9.87 (s, 1H), 8.29-8.27 (m, 1H), 8.22 (s, 1H), 7.69 (s, 1H), 7.40-7.36 (m, 1H), 7.05-7.02 (m, 1H), 6.41 (d, J=7.8 Hz, 1H), 3.94-3.84 (m, 4H), 3.50 (d, J=13.3 Hz, 1H), 3.44-3.36 (m, 1H), 3.20 (d, J=13.4 Hz, 1H), 3.07-3.02 (m, 1H), 2.19-2.11 (m, 2H), 2.06-1.94 (m, 2H), 1.94-1.83 (m, 2H), 1.75-1.66 (m, 3H), 1.62-1.57 (m, 1H), 1.49-1.34 (m, 1H).
