Cadiot–Chodkiewicz coupling


The Cadiot–Chodkiewicz coupling in organic chemistry is a coupling reaction between a terminal alkyne and a haloalkyne catalyzed by a copper salt such as copper bromide and an amine base. The reaction product is a 1,3-diyne or di-alkyne.
The reaction mechanism involves deprotonation by base of the terminal alkyne proton followed by formation of a copper acetylide. A cycle of oxidative addition and reductive elimination on the copper centre then creates a new carbon-carbon bond.

Scope

Unlike the related Glaser coupling the Cadiot–Chodkiewicz coupling proceeds selectively and will only couple the alkyne to the haloalkyne, giving a single product. By comparison the Glaser coupling would simply produce a distribution of all possible couplings.
In one study the Cadiot–Chodkiewicz coupling has been applied in the synthesis of acetylene macrocycles starting from cis-1,4-diethynyl-1,4-dimethoxycyclohexa-2,5-diene. This compound is also the starting material for the dibromide through N-bromosuccinimide and silver nitrate:
The coupling reaction itself takes place in methanol with piperidine, the hydrochloric acid salt of hydroxylamine and copper bromide.