Alkynes: Structure and Reactions

Alkynes are unsaturated hydrocarbons characterized by a carbon-carbon triple bond, making them structurally similar to alkenes. Like alkenes, alkynes are nucleophilic and participate in addition reactions, where electron-rich regions of the triple bond interact with electrophiles. However, what sets alkynes apart is their ability to undergo unique acetylide chemistry. The terminal hydrogen in alkynes is relatively acidic, allowing for the formation of acetylide ions when treated with a strong base. These acetylide ions are powerful nucleophiles, making them valuable intermediates in organic synthesis.

A notable application of acetylide chemistry is in the synthesis of Efavirenz, an important reverse transcriptase inhibitor used in the treatment of HIV. In this synthesis, an acetylide ion is generated and added to a ketone, forming a chiral alcohol intermediate that is crucial for building the Efavirenz molecule.

The asymmetric synthesis of Efavirenz was originally reported by Merck by the enantioselective addition of lithium cyclopropyl acetylide to trifluoroacetophenone derivative in the presence of an excess amount of an ephedrine derivative as a chiral source to form intermediate A, a precursor to Efavirenz.