Benzophenone → Combretastatin A4

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-phenylpyridine-N-oxide (0.127 g, 0.74 mmol) and (R,R)-(−)-[N,N1-bis(3,5-di-tert-butylsalicylidene)-1.2-cyclohexanediaminoat(2-)]manganese(III) chloride (Palucki, et al., Highly Enantioselective, Low-Temperature Epoxidation of Styrene, J. Am. Chem. Soc. 1994, 116, 9333-9334) (0.024 g, 0.037 mmol) in a 50 mL flask was added a solution of 3′[(tert-butyldimethylsilyl)oxy]combretastatin A-4(1c, 0.80 g, 1.86 mmol) in 3 Ml of ethyl-acetate (or methylene chloride). The mixture was stirred at 4° C. for 20 minutes followed by addition of an aqueous 0.50 M NaOCl solution (6.32 mL, 3.16 mmol) via syringe. The temperature remained at 4° C., and reaction progress was monitored by TLC (4:1 hexane-EtOAc). After 5 h, the reaction mixture was warmed to room temperature, and the aqueous phase removed. The organic layer was washed successively with water (2×10 mL) and brine (10 mL) and dried over anhydrous Na2SO4. Filtration and solvent removal in vacuo gave a brown residue that was subjected to flash column chromatography (4:1 hexane-ethyl acetate, 1″×12″ column). The silyl ether protected benzophenone 3a (Rf=0.27) was collected as a yellow oil. A second flash column chromatographic separation was necessary for final purification. Consistent 10% yields were obtained based on conversion of combretastatin A-4 silyl ether to phenstatin (3b, see below).

Provenance & Evidence