SolutionsThe Sonogashira coupling
Exercise 1
Propose a synthesis of diphenylacetylene from iodobenzene and trimethylsilylacetylene. Why is the latter used instead of acetylene?
First Sonogashira coupling (PdCl2(PPh3)2, CuI, Et3N): PhI + HC≡CSiMe3 → PhC≡CSiMe3. Deprotection with K2CO3 in MeOH or with fluoride (TBAF): PhC≡CH. Second coupling with PhI: PhC≡CPh. Acetylene is a gas, difficult to meter, and with its two C–H bonds it would react at both ends; the trimethylsilyl group blocks one of them and is easily removed.
Exercise 2
When a Sonogashira coupling is run without degassing the solvent, a substantial amount of 1,4-diphenylbuta-1,3-diyne is obtained from phenylacetylene. Explain its formation.
It is the Glaser coupling product: oxygen oxidizes the copper(I) acetylide and two alkynyl groups couple with each other (PhC≡C–C≡CPh). It is avoided by working under an inert atmosphere, with degassed solvents, or with copper-free variants.