Allyl chloroformate → Allyl(6S,7S,10R)-2-(tert-Butyldimethylsiloxy)-6-[(Z)-6-(tert-butyldimethylsilyl)-3-hexene-1,5-diynyl]-7,8,9,10-tetrahydro-10-hydroxy-9,9-dimethoxy-7-methyl-5(6H)-phenanthridinecarboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of ethylmagnesium bromide in tetrahydrofuran (1.0M, 13.6 mL, 13.6 mmol, 0.90 equiv) was added to a solution of (7S, 10R)-2-(tert-butyldimethylsiloxy)-7,8,9,10-tetrahydro-9,9-dimethoxy-7-methyl-10-phenanthridinol (17, 6.10 g, 15.1 mmol, 1 equiv) in tetrahydrofuran (30 mL) at -78° C. The mixture was stirred in an ice bath for 10 min, then was cooled to -78° C. In a separate flask, a solution of ethylmagnesium bromide in tetrahydrofuran (1.0M, 22.7 mL, 22.7 mmol, 1.50 equiv) was added to a solution of tert-butyl [(Z)-3-hexene-1,5-diynyl]dimethylsilane (18, 5.75 g, 30.2 mmol, 2.00 equiv) in tetrahydrofuran (20 mL) at 0° C. The resulting solution was warmed to 23° C., then was heated briefly to reflux with a heat gun. After the mixture had cooled to 23° C., it was transferred via cannula over 3 min to the cold solution of magnesium alkoxide derived from the TBS quinoline. Allyl chloroformate (1.20 mL, 14.4 mmol, 2.00 equiv) was added, and the solution was stirred in an ice bath for 2 h. The reaction mixture was partitioned between aqueous phosphate buffer solution (pH 7, 0.05M in sodium hydrogen phosphate and 0.05M in potassium dihydrogen phosphate, 150 mL) and ethyl acetate (150 mL). The aqueous layer was separated and extracted further with ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate and were concentrated. The residue was purified by flash column chromatography (10% ethyl acetate-hexanes initially, grading to 20% ethyl acetate-hexanes) to afford allyl (6S, 7S, 10R)-2-(tert-butyldimethylsiloxy)-6-[(Z)-6-(tert-butyldimethylsilyl)-3-hexene-1,5-diynyl]-7,8,9,10-tetrahydro-10-hydroxy-9,9-dimethoxy-7-methyl-5 (6H)-phenanthridinecarboxylate (19) as a light yellow foam (9.16 g, 89%). The other product, structure 20, was not used.

Provenance & Evidence