First published on April 28, 2010
Girard et al, Molecules, doi:10.3390/molecules15053087
After a 2006 report (Org. Lett. 8, 1689) on a solid phase supported Copper (1+) catalyst for alkyne-azide click reaction ), this article showcases the use of the catalyst system in an automated synthesis of a 96 product-sized triazole library.
Several interesting things. First, they use the automated chemical synthesis station for high-throughput (ChemSpeed ASW-2000). Second, HNMR monitoring of the click reaction was an elegant kinetics measurement. Third, the stability and recycled use of the catalyst are impressive – 5 cycles over 5 days!
At least two questions can be asked. First, Cu(1+) leaching may still be a problem in certain applications / systems / solvents. Second, the resin swelling was not considered in the solvent effect for the click reaction.
An ideal solid-supported catalyst needs have the following: Cu(1+) should be chelated in a kinetically / thermodynamically stable complex for zero leaching yet highly reactive in catalysis; the immobilization should allow reaction components to access the catalyst easily; the resin should be insensitive to solvent choice, preferably including water.
A long way to go!