Osmium tetroxide mixture with sodium periodate

The Step 7 product (113 mmol) dissolved in 600 ml dioxane was treated with 200 ml water and 4 ml 4% aqueous solution of osmium tetroxide, then stirred 5 minutes, and treated with sodium periodate (469 mmol). The mixture was heated 3 hours at 35°C, then cooled to ambient temperature, and diluted with 11 EtOAc. The solution was then washed with water, dried, and concentrated. The residue was recrystallized using THF and 15 g of product was isolated. The remaining filtrate was purified by chromatography with silica gel and EtOAc/hexanes, 1 1, so that a total product yield of 44% was observed. 

The Step 5 product (410 mg) dissolved in 15 ml THF and 5 ml water was treated with 1.1ml 2.5% solution osmium tetroxide in t-butyl alcohol followed by the portionwise addition of sodium periodate (686 mg), then stirred overnight at ambient temperature. The mixture was concentrated and the residue dissolved in 26 ml... 

In a typical example, sodium periodate (18.2 g, 85 mmol) was added in small portions over a 45 min period to l,4-dioxa-6-acetyl-6-allylspiro[4.5]decane (8.9 g, 40 mmol) and osmium tetroxide (0.10 g, 0.39 mmol) in a solution of THF (126 mL) and water (42 mL) at room temperature. The mixture was stirred for 2 h at this temperature during which time the black slurry turned brown. Water (600 mL) was introduced, and the mixture was extracted with ether. The extract was dried over anhydrous magnesium sulfate and stripped of solvent to give 7.4 g of crude aldehyde. (Because osmium tetroxide is a toxic and volatile irritant, all preparations should be carried out in a fume hood with use of adequate personal protection, gloves and safety glasses.) Other examples of the use of this reagent have b n summarized in Table 5. 

Reductive cyclization has been used in a novel, recent synthesis of the alkaloids ( )-isoretronecanol (22) and ( )-trachelanthamidine (23) by Borch and Ho. Condensation of the dianion derived from methyl acetoacetate with Z-l,4-dichlorobut-2-ene, followed by cyclization with sodium meth-oxide yielded the cycloheptenone ester intermediate (32) (Scheme 2). Reductive amination of this ketoester with sodium cyanoborohydride and ammonium nitrate gave a mixture of the diastereoisomeric aminoesters 33 and 34. Oxidation with osmium tetroxide and periodate, followed by reductive cyclization, again using sodium cyanoborohydride, gave the two pyrrolizidine esters 35 and 36 in a ratio of 1 2 [gas-liquid chromatography (GLC) analysis]. The esters were separated by preparative layer chromatography, and lithium aluminum hydride reduction of the individual esters gave the two pyrrolizidine alkaloids 22 and 23. 

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