Ruthenium-catalyzed formal sp3 C–H activation of allylsilanes/esters with olefins: efficient access to functionalized 1,3-dienes†

Ru-catalysed oxidative coupling of allylsilanes and allyl esters with activated olefins has been developed via isomerization followed by C(allyl)–H activation providing efficient access to stereodefined 1,3-dienes in excellent yields. Mild reaction conditions, less expensive catalysts, and excellent regio- and diastereoselectivity ensure universality of the reaction. In addition, the unique power of this reaction was illustrated by performing the Diels–Alder reaction, and enantioselective synthesis of highly functionalized cyclohexenone and piperidine and finally synthetic utility was further demonstrated by the efficient synthesis of norpyrenophorin, an antifungal agent.


Compound 3da
Following general procedure, 3da was obtained as a pale yellow oil (30:

2.2b. Synthesis of compound 9
To a solution of 5gh (1.3 g, 6.5 mmol, 1.0 equiv) in ethanol (15 ml), added potassium carbonate (815 mg, 5.9 mmol, 0.9 equiv) in four portions over 5 min and reaction mixture was allowed to stirred for 40 minutes at room temperature. Then reaction mixture was quenched with water and extracted with ethyl acetate (15 ml Χ 3), washed with brine, dried over anhydrous Na2SO4, concentrated in vacuo and purified by column chromatography (7:3 petroleum ether/ethyl acetate) furnishing the enone 9 (816 mg, 5.2 mmol, 80%) as a yellow liquid.

2.2c.Synthesis of compound 13 1
To a suspension of catalyst (52 mg, 0.16 mmol, 0.1 equiv), enone 9 (250 mg, 1.60 mmol, 1 equiv) and acetic acid (10 μl, 0.16 mmol, 0.1 equiv) in methanol (7 ml) was added heptaldehyde (0.45 ml, 365 mg, 3.2 mmol, 2 equiv) at 0 o C. The reaction mixture was stirred for 1 h at the same temperature and then warmed to room temperature for 3 h. The solution was partitioned between ethyl acetate and saturated NaHCO3. The organic phase was separated and aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated. Purification of the residue by flash column chromatography (silica gel) eluting with 10:1 petroleum ether/ethyl acetate afforded the Michael adduct 13 (310 mg, 1.152 mmol, 72%) as a pale-yellow liquid.

2.2d. Synthesis of compound 11 1
To a solution of Michael adduct 13 (100 mg, 0.37 mmol) in 4 mL of DCM, was added DBU (113 ml, 0.74 mmol, 2.0 equiv) at 0 o C. After it was stirred for 1 h at 0 o C, the solution was warmed to room temperature and stirred for 2h. The reaction mixture was partitioned between ethyl acetate and brine. The organic phase was separated and aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography (silicagel, 10:1 petroleum ether/ethyl acetate as eluent) to give the corresponding cyclohexanone.
To a solution of aldol reaction product (70 mg, 0.25 mmol) in DCM (3 mL) were added MsCl (60 μl, 0.77 mmol, 3.0 equiv ) and Et3N (0.19 ml, 1.5 mmol, 6.0 equiv) at 0 o C. After the reaction mixture was stirred for 1h at 0 o C, and 6 h at 25 o C, it was partitioned between ethyl acetate and brine. The organic phase was separated and aqueous phase was extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated. The residual oil was purified viaflash column chromatography (silica gel, 20:1 petroleum ether/ethyl acetate as eluent) to afford the corresponding cyclohexenone 11 (38mg, 0.15mmol, 60%).

2.3c. Synthesis of compound 21
Using a Dean-Stark trap, ethylene glycol (1.3 ml, 23.36 mmol, 30 equiv.) was refluxed in benzene (5 mL) for 1 hour. Upon cooling, compound 20 (250 mg, 1.16 mmol) in benzene (2 mL) and p-toluene sulfonic acid (10 mg, 0.046 mmol, 0.04 equiv.) were added to the solution and the resulting mixture was heated to reflux under a condenser for 1.5 hours (heating for more than 1.5 hours resulted in decomposition of product). The solution was then cooled and quenched with NaHCO3 (10 mL). The resulting mixture was extracted with EtOAc (3 x 10 mL), washed with water (80 mL) and brine (80 mL), dried over Na2SO4 and concentrated. The crude product was purified by column chromatography (3 : 1.5:: Pet ether : EtOAc) to obtain of the pure ketal 21 (254 mg, 0.986 mmol, 85% yield) as a yellow liquid.

2.3e. Synthesis of norpyrenophorin 14 3
Trimethylaluminium (0.925 mL of a 2 M solution, 1.85 mmol, 10 equiv) in toluene was added to a 5 mL side-arm flask containing selenium powder (150 mg, 1.924 mmol, 10.4 equiv) at 0 o C and refluxed till the selenium powder had reacted completely, the resulting mixture was cooled to room temperature. An aliquot of Me2SeAlMe (10 μl, 1.1 mmol) was transferred by syringe to a solution containing compound 22 (40 mg, 0.185 mmol) in toluene (1.2 mL) at 0 °C. After 28 h of heating at reflux, the yellow solution was warmed to room temperature over a period of 30 min and treated with sodium sulfate. The solution was then diluted with dichloromethane, washed with water six times and treated with sodium hydrogen carbonate. The solution was then dried with brine and anhydrous magnesium sulfate. The solvent was removed under vacuum from the yellow solution and the residue wasdissolved in acetone (0.75 ml), added p-toluene sulfonic acid (3 mg, 0.0081 mmol, 0.1 equiv) at 0 o C and stirred for 4 hours at room temperature. then reaction mixture was quenched with NaHCO3 solution and extracted with EtOAc, dried over Na2SO4 and concentrated. The crude product was purified by column chromatography(1:1 :: Pet ether : EtOAc) furnishing the norpyrenophorin 14 3 (6 mg, 0.0214 mmol, 23% in two steps).