Research Projects

The study proposes the use of 2-butynoyl pyrazole (I) as a potential nucleophilic precursor for various C–C bond-forming reactions. The deprotonative activation of I is challenging due to its higher pKa value than those of internal alkyne tethered to aldehydes and ketones. To prevent propargyl to allenyl isomerization, a highly reactive electrophilic partner is suggested. Three distinct synthetic routes for asymmetric propargylation of various electrophiles are proposed, using 2-butynoyl pyrazole (I) as the pronucleophile in the presence of a copper(I)-BOX (bisoxazoline) catalytic system and a Brønsted base. In asymmetric propargylic substitution reactions, the in situ generated metal-allenylidene intermediate undergoes various propargylation substitution reactions with a wide range of nucleophiles. Nucleophiles with high basicity have been explored, but they have not been explored due to their detrimental effect on the outcome of propargylic substitution reactions. The study proposes an asymmetric decarboxylative propargylic substitution reaction of propargylic compounds linked to cyanoacetic acids/2-(2-azaaryl)acetic acids using a Cu(I)-chiral BOX catalytic system. This approach allows for the in situ generation of the required active nucleophile and electrophile under mild reaction conditions.