Economic Large-Scale Synthesis of o- and m-Diphenylphosphinobenzoic Acids

Abstract

An efficient and simple to perform large-scale synthesis of o-and m-diphenylphosphinobenzoic acids is presented. In a single step, both useful carboxylic acid-functionalized phosphines can be accessed starting from the same inexpensive bulk chemicals o-chlorobenzoic acid, triphenylphosphine, and sodium. In both cases the formation of the desired product is controlled by the ratio of the starting materials only. Additionally, X-ray crystallographic data are reported for both products.Phosphines are widely applied and important donor ligands for transition metal catalysis. 1 Of particular use are phosphines equipped with appropriate functional groups, which allow for a modular ligand design through attachment to a variety of chiral and achiral backbones. Interesting examples of this class of ligands are the C2-symmetric Trost ligands, widely applied for asymmetric palladium-catalyzed allylic substitution. 2 These ligands are constructed by a modular design. Thus, chiral diols or diamines are connected through an ester or an amide linkage to the phosphine-binding post, with o-diphenylphosphinobenzoic acid (1, o-DPPBA) being the most important phosphine building block (Figure 1). Additionally, o-DPPBA (1) has found application as mediator in Staudinger ligation reacions 3 as well as catalyst-and reagent-directing group in a number of transition-metalcatalyzed and -mediated reactions. 4 Among them are the directed rhodium-catalyzed hydroformylation, 5c,6 conjugate addition 5 as well as the directed copper-mediated allylic substitution with Grignard reagents. 7 This methodology proved highly reliable for the construction of tertiary and quaternary stereocenters providing exceptional levels of acyclic stereocontrol, which has been applied in several natural product syntheses. 8 A drawback of this methodology has been the rather high costs of commercial o-DPPBA.The regioisomer of o-DPPBA (1) the m-diphenylphosphinobenzoic acid (2, m-DPPBA) is the basis for a variety of ligands (Figure 1), which have been applied for the Heck reaction and in allylic alkylation. 9 Moreover, we recently reported on the use of m-DPPBA (2) as a building block for supramolecular metallopeptide ligands for hydroformylation and asymmetric hydrogenation. 10 Figure 1 The o-and m-diphenylphosphinobenzoic acids 1 and 2Known total syntheses of m-and o-DPPBA (1,2) rely on halogen-lithium exchange reactions, on the use of Grignard reagents 11 or on the applications of transition-metalmediated coupling reactions. 12 Most of these syntheses suffer from low yields, multistep processes, or expensive starting materials. 11-13