Nitrogen heterocycles continue to be highly regarded as valuable bioactive molecules and important precursors to pharmaceuticals. A novel N-heterocycle functionalization method has been developed through the enantioselective alkynylation of substituted quinolones. This synthesis utilizes copper (I) bis(oxazoline) catalysis to selectively add phenylacetylene derivatives on the 2-position of 4-quinolones. The generated stereocenter is created with high levels of enantiocontrol, up to 96% e.e.. The mechanism of the reaction was investigated through a Linear Free Energy Relationship study to probe the effects of various functional groups on both the phenylacetylene and the aromatic ring of the quinolone. Hammett plots suggested an accumulation of negative charge at the phenylacetylene in the enantio-determining step. We hypothesize that electron-withdrawing groups, which demonstrated the highest level of enantioselectivity, stabilize the transition state through resonance and inductive effects.

• This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

Creator

• Burns, Sean
• Richins, Margaret

Publisher

• Worcester Polytechnic Institute

Identifier

• 65946
• E-project-042822-164549

Advisor

• Mattson, Anita Elaine

Year

• 2022

Sponsor

• National Institutes of Health

Date created

• 2022-04-28

Resource type

• Major Qualifying Project

Major

• Chemistry
• Biochemistry

Rights statement

• In Copyright