pent-2-enamide

Conditions: temp:42.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of (3R,4R,5R)-5-ethenyl-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-4-ol (18 mg, 0.099 mmol) was prepared in ClCH2CH2Cl (200 μL) at 23° C. under an open atmosphere. To a stirred solution of (S,Z)-5-((2R,3R,5S,6S)-2,5-dimethyl-6-((E)-3-methylpenta-2,4-dienyl)-tetrahydro-2H-pyran-3-ylamino)-5-oxopent-3-en-2-yl morpholine-4-carboxylate (26 mg, 0.062 mmol) in ClCH2CH2Cl (200 μL) was added the solution of (3R,4R,5R)-5-ethenyl-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-4-ol (100 μL), benzoquinone (1.4 mg, (0.012 mmol), followed by Grela catalyst (1.5 mg, 2.2 μmol) at 23° C. under an open atmosphere. The reaction mixture was then heated to 42° C. After 3 h at the same temperature, additional Grela catalyst (1.5 mg, 2.2 μmol) and (3R,4R,5R)-5-ethenyl-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-4-ol (100 μL) were added. After 11 total hours, the reaction was concentrated under reduced pressure. The resulting residue was purified by flash chromatography (10→80% EtOAc in hexanes) on silica gel (8 mL) to give (2Z,4S)-4-[(morpholinylcarbonyl)oxy]-N-[2R,3R,5S,6S)-tetrahydro-6-[(2E,4E)-5-[(3R,4R,5R)-4-hydroxy-7,7-dimethyl-1,6-dioxaspiro[2.5]oct-5-yl]-3-methyl-2,4-pentadien-1-yl]-2,5-dimethyl-2H-pyran-3-yl]-2-Pentenamide (10.4 mg, 29%), and a mixture of (S,Z)-5-((2R,3R,5S,6S)-2,5-dimethyl-6-((E)-3-methylpenta-2,4-dienyl)-tetrahydro-2H-pyran-3-ylamino)-5-oxopent-3-en-2-ylmorpholine-4-carboxylate and (3R,4R,5R)-5-ethenyl-7,7-dimethyl-1,6-dioxaspiro[2.5]octan-4-ol (22.1 mg). After 11 total hours, the reaction was concentrated under reduced pressure The resulting residue was purified by flash chromatography (10→80% EtOAc in hexanes) on silica gel (8 mL)