SolutionsCross-coupling reactions
Exercise 1
Which coupling would you choose to attach a phenyl group to C4 of ethyl 4-iodobenzoate: Kumada, Negishi or Suzuki? Justify your answer.
Not Kumada, because phenylmagnesium bromide would attack the ester. Both Negishi (PhZnCl, which tolerates the ester) and Suzuki (PhB(OH)2, with a mild base such as K2CO3) would work; in practice Suzuki is preferred, because phenylboronic acid is a stable, commercially available, low-toxicity solid.
Exercise 2
1-Bromo-4-chlorobenzene is treated with one equivalent of phenylboronic acid, Pd(PPh3)4 and Na2CO3. What product is formed? Explain.
4-Chlorobiphenyl. Oxidative addition is much faster into the weaker C–Br bond than into C–Cl, and with a triphenylphosphine catalyst the chloride hardly reacts. The chloride can then be coupled in a second step with a more active catalyst.