The Heck reaction in the production of fine chemicals

Abstract

An overview is given of the use of the Heck reaction for the production of fine chemicals. Five commercial products have been identified that are produced on a scale in excess of 1 ton/year. The herbicide Prosulfuron(tm) is produced via a Matsuda reaction of 2-sulfonatobenzenediazonium on 3,3,3-trifluoropropene. The sunscreen agent 2-ethylhexyl p-methoxy-cinnamate has been produced on pilot scale using Pd/C as catalyst. Naproxen(tm) is produced via the Heck reaction of 2-bromo-6-methoxy-naphthalene on ethylene, followed by carbonylation of the product. Monomers for coatings are produced via a Heck reaction on 2-bromo-benzocyclobutene. A key step in the production of the antiasthma agent Singulair(tm) is the use of the Heck reaction of methyl 2-iodo-benzoate on allylic alcohol (18) to give ketone (20). The high cost of palladium has spurred much research aimed at the development of more active palladium catalysts. Ligandless catalysts are very attractive for production, but work only on reactive substrates. Palladacycles are much more stable than Pd-phosphine complexes and can be used at higher temperatures. The same effect has been reached with pincer ligands. Bulky ligands lead to coordinatively unsaturated Pd-complexes, which are highly active for the Heck reaction. Recycle of palladium catalysts is also very important to reduce cost. Immobilization of catalysts by attaching ligands to solid support is not very useful, because of leaching and reduced activity. In ligandless Heck reactions the catalyst can be precipitated on carriers such as silica, dicalite, or celite. This material can be restored to its original activity by treatment with I2 or Br2.Key words: homogeneous catalysis, palladium, arylation, olefination, ligandless, catalyst recycle.