Carbon Dioxide → Propiolic Acid

Participants

Reaction Steps

Dibromoolefin intermediate XIX is then converted to ethynyl intermediate XX. Treatment of the dibromoolefin intermediate with about two equivalents of n-butyllithium produces the lithium acetylide XX, wherein R13 is Li. This transformation is typically carried out in a polar organic solvent, such as tetrahydrofuran, at a temperature of about -78° C. to about 25° C. The lithium acetylide is reacted with electrophiles, such as methoxymethyl chloride, 5-bromomethyl-3-methoxyisoxazole, 3-diphenylmethoxy-4-iodomethyl-1,2,5-thiadiazole, carbon dioxide, tetrazole disulfide, and the like, to prepare the formula I compounds. In a typical example, the lithium acetylide is treated with solid CO2 at a temperature of about -78° C. to about -60° C. to produce propargylic acid intermediate XX wherein R13 is CO2H. This compound may be further modified as described herein.

Provenance & Evidence