Greener Approaches to Cross-Coupling - New Trends in Cross-Coupling: Theory and Applications - page 680

N-Butyl-N,N,N 0 ,N 0 -tetramethylguanidinium acetate is an IL, but is in
equilibrium with acetic acid and the neutral guanidine. When used as a
solvent for Heck coupling, the free guanidine can serve as a ligand for pal-
ladium. 182 Good yields were obtained with aryl iodides and bromides and
even activated aryl chlorides at 140 1C. As the reaction proceeds, the acetate
anion is replaced by bromide and acetic acid is formed. The IL-Pd solution
could be reused until all of the acetate was consumed. Analysis of the IL-Pd
solution after one reaction cycle showed that about 10% of the original
palladium had been lost after removal of the product by extraction.
14.4 Alternative Reaction Conditions to Improve
Sustainability
14.4.1 Microwave Heating
Microwave irradiation allows for rapid and even heating of reaction mix-
tures, unlike traditional thermal heating. As a result, microwave heating can
provide more ecient thermal promotion of reactions with lower energy
demand. The speed of heating can dramatically accelerate reaction rates
compared with thermal heating. For microwave heating to be effective, the
solvent must have a strong dipole. Water is an ideal solvent for microwave-
promoted reactions because of its strong interaction with microwave
radiation. Microwave heating is often used with catalysts that require high
reaction temperatures (4100 1C) to provide high reaction rates.
Microwave heating was first applied to aqueous-phase palladium-
catalyzed Suzuki coupling of PEG-supported aryl bromides as part of a rapid-
throughput synthesis approach. 183 Using microwave heating, high yields
were obtained with a ligand-free catalyst in PEG-water with a reaction time
of 2-4 min. Suzuki coupling of aryl chlorides catalyzed by Pd/C was carried
out at 120 1C using microwave heating. 115,184 Microwave irradiation gave
rates that were 30 times higher than those with conventional heating and
three times higher than those with ultrasound irradiation in aqueous-phase
Suzuki coupling catalyzed by palladium nanoparticles supported on PVP. 185
Catalyst loadings as low as 2.5 ppm have been used for the Suzuki coupling
of aryl bromides under microwave irradiation. 186 Microwave irradiation has
also been applied to Hiyama, 53 Sonogashira 187 and Heck 188 couplings. a-
Arylation of the protected glycine derivative 30 in water gave amino acid 31
(Scheme 14.28). 88 Copper-catalyzed Sonogashira couplings of aryl iodides
can be carried out in o 1 h under microwave irradiation compared with 24 h
for conventional heating. 189
14.4.2 Ultrasound
Ultrasound irradiation has been shown to accelerate many reactions,
allowing them to be completed with shorter reaction times than with ther-
mal activation. As a result of the shorter reaction times and lower reaction