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SSG4
Winter 06
Experimental Page Corner
Experimental
for

"Divergent Enantioselective Synthesis of (-)-Galanthamine and (-)-Morphine"
Trost, B.M.; Tang, W.; Toste, F.D. J. Am. Chem. Soc. 2005, 127, 14785-14803.

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Synthesis from 69 to 70

1.0 M sodium hexamethyldisilamide(1) (3.5 mL, 3.5 mmol) was added to a precipitate of methoxymethyltriphenylphosphonium bromide(2) (1.4 g, 4.08 mmol) in THF(3) (5 mL) at 0 0C. The suspension was irradiated with a sonicator(4) for 1 hr at 0 0C. The resulting solution was added to 69 (370 mg, 0.986 mmol) in THF (5 mL). The solution was continued to be irradiated at 0 0C for 1 hr. The solution was then diluted with diethyl ether(5) (100 mL), washed with 1N sodium bisulfate(6) (50 mL), dried with MgSO4, and concentrated in va cuo(7). Flash chromatography (2:1 petroleum ether: diethyl ether) was then performed to yield 70 (254 mg, 64 %), which was then characterized (10:1 mixture of Z:E)

Synthesis from 70 to 20

Boc-protected 70 (125 mg, 0.310 mmol) in methylene chloride (2 mL) was deprotected with trifluoroacetic acid(8) (250 mL, 2.19 mmol). The mixture was left at room temperature for 1 hr and then concentrated in vacuo to produce a solid. The solid was dissolved in methanol (3 mL), along with 4Å molecular sieves. The mixture was heated under reflux for 4 hrs, cooled to 0 0C, and sodium cyanoborohydride(9) (40 mg, 0.636 mmol) was added. The solution was then diluted with methylene chloride (25 mL) after 1 hr and then filtered. The filtrate was washed with brine (10 mL), dried with MgSO4, and concentrated in vacuo. Flash chromatography (5 % methanol: methylene chloride) was performed to yield 20 (254 mg, 64 %), which was then characterized.

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