Carboxylate directed cross-coupling reactions in the synthesis of trisubstituted benzoic acids.
The carboxylate anion has been used as a directing group to effect selective ortho-substituted derivatives 3 (>99:1 selectivity 50-80% yield). The solvent, base, and equivalents of base are the determining factors for the success of this reaction. The directing effect can be reversed by the appropriate use of phosphine ligands to prepare the para-substituted 4 selectively (ca. 12:1 selectivity).
Houpis
Ioannis N
IN
Johnson and Johnson PRD, API Development, Turnhoutseweg 30, 2340 Beerse, Belgium. yhoupis@its-jnj.com
Huang
Changkang
C
Nettekoven
Ulrike
U
Chen
Jason G
JG
Liu
Renmao
R
Canters
Martine
M