Despite advances in the Suzuki–Miyaura cross-coupling process,[1] the need for an operationally simple and general system remains. The minimum criteria for an optimum system that must be met include: 1) a broad substrate scope, 2) the ability to make truly hindered biaryls, 3) the ability to operate at low levels of catalyst for a range of substrates not just with the most simple examples (eg, other than phenyl boronic acid),[2] and 4) the ability to operate at room temperature. Moreover, it is most desirable to develop protocols that do not necessitate the use of a glovebox. Herein we report a catalyst system based on a new ligand that meets the above four criteria, has unprecedented scope, reactivity, and stability, uses only commercially available, air-stable components, and is experimentally simple to employ. Our previous work on cross-coupling methodology demonstrated that dialkylphosphanylbiphenyls were excellent supporting ligands. We have reported that these can be prepared by the addition of an aryl Grignard reagent to an insitu-generated benzyne intermediate, followed by trapping of the newly formed organomagnesium complex with ClPR2.[3] The thought process that led to the design of the new ligand 1 is shown in Scheme 1.

Mechanistic studies in our laboratory indicated that the elimination of ortho hydrogens on the bottom ring (that not bearing the dialkylphosphanyl group) was important for catalyst activity and longevity.[4] We believe that this is due to two effects: 1) prevention of cyclometalation [5](to form a palladacycle), which diminishes catalyst lifetime, and 2) increased steric bulk relative to complexes with two ortho hydrogens. We also feel that it is important that the two methoxy groups are smaller in size than two alkyl groups as in our previously reported ligands. Moreover, the lone pairs of the alkoxy groups might interact with the Pd center and/or add electron density to the ligand backbone. The latter could be important as the interaction of the metal with the bottom ring is well documented [6] and could help stabilize intermediate complexes.[2c, 7] Furthermore, the 1, 3-dimethoxybenzene moiety offers the advantage that it can be installed by means