Tsuji–Wacker-Type Oxidation beyond Methyl Ketones: Reacting Unprotected Carbohydrate-Based Terminal Olefins through the “Uemura System” to Hemiketals and α,β-Unsaturated Diketones

Aerobic Pd(AcO)2/pyridine-catalyzed oxidation of unprotected carbohydrate-based terminal alkenes was studied. In accordance with previous reports, the initial reaction step gave methyl ketones. However, our substrates partially gave subsequent α,β-water elimination and alcohol oxidation to α,β-unsaturated 2,5-diketones. Upon increasing the pressure of O2, the reaction was shifted toward formation of α,β-epoxy-2-ketones. The reactions were stereoselective and gave up to quantitative conversions. However, isolated yields were substantially lower because of the complexity of the product mixtures.

One equivalent carbohydrate or glyceraldehyde was dissolved in deionized water (to a 0.2 M solution). Three equivalents tin powder and two equivalents allyl bromide was added and the reaction mixture was stirred at room temperature overnight. Dilution in ethanol followed by filtration through celite, and finally evaporation of solvents gave the polyol product. For threo-isomer of allylated D-mannose (1), synthesis and additional analytical information can be found in the literature. [2,3] For allylated D-glucose (2), synthesis, 1 H and 13 C NMR, and other analytical information can be found in the literature. [3] For 5-Hexene-1,2,3-triol (3), synthesis, , 1 H and 13 C NMR, and other analytical information can be found in the literature. [4,5]

Tsuji-Wacker-type oxidation of allylated polyols
The reaction followed literature procedure, but with minor alterations. [6] In a typical experiment, a preheated (60 ˚C) autoclave was charged with a solution of polyol (1.50 mmol, 1.0 eq), Pd(OAc)2 (0.45 mmol, 0.3 eq) and pyridine (0.90 mmol, 0.6 eq) in isopropanol (10 ml). The autoclave was then filled with molecular oxygen (1 or 2 bar). The reaction mixture was vigorously stirred at 60 ˚C for 20 hours. Any possible formed black precipitate (palladium black) was filtered off. Evaporation of solvents gave the crude mixture of products (and palladium complexes). GCMS and NMR analyses of the crude mixture were used for calculating the observed conversion and for characterizing the formed products. As the spectra of the two isomers 7a and 7b were overlapping the coupling constants for some signals of isomer A were not solved. However, the chemical shifts for 1 H and 13 C signals for the two isomers were solved using, in addition to 1  Product 12 was very unstable and had completely reacted to a mixture of products before HRMS analysis. However, HRMS was done after acetylation to 19 (look at page S13). data is in accordance with literature data. [9] Product 16 was formed through olefin migration. Similar Pd(II)-catalyzed olefin migrations have been reported, also for the formation of 16 from 4. [10,11]

Additional investigations into the Tsuji-Wacker-type oxidation
The reaction with 1 was also performed under argon atmosphere, in the absence of oxygen, using 2-propanol, Pd(OAc)2, and allylated polyol which had been flushed with argon for one hour to remove oxygen. Interestingly, the reaction had an observed conversion of 60 % after 24 hour of stirring at 60 ˚C, and products 5 and 6 were formed in a 3:4 ratio.
When a mixture of erythro-and threo-isomers of 1 reacted in the oxidation system using 2 bar molecular oxygen, a mixture of erythro-and threo-isomers of the products were retrieved (5, 7a and 7b). The mixture was acetylated, and the products were separated by column chromatography using petroleum ether and ethyl acetate as eluents. [See NMR for the epoxides 17 and erythro-17]

Acetylation of reaction mixtures
The acetylation reaction followed literature procedure. [12] The crude reaction mixture was dissolved in pyridine. Acetic anhydride (15 mmol, 10 eq) was added and the reaction was S10 vigorously stirred at room temperature for 3 hours. The reaction was quenched by addition of methanol (1 ml), and the solvents were evaporated.
During the acetylation reaction, any ring closed product (except 6) was opened to the corresponding open chain ketone derivative. The epoxides 7a and 7b gave the single product 17 when ring opened. Additionally the open chain methyl ketone derivatives of 5 and 12 were further hydrolyzed to α-unsaturated methyl ketones (18 and 19).