Structural, Kinetic, and Computational Characterization of the Elusive Arylpalladium(II)boronate Complexes in the Suzuki–Miyaura Reaction

Abstract

The existence of the oft-invoked intermediates containing the crucial Pd-O-B subunit, the "missing link", has been established in the Suzuki-Miyaura cross-coupling reaction. The use of low-temperature, rapid injection NMR spectroscopy (RI-NMR), kinetic studies, and computational analysis has enabled the generation, observation, and characterization of these highly elusive species. The ability to confirm the intermediacy of Pd-O-B-containing species provided the opportunity to clarify mechanistic aspects of the transfer of the organic moiety from boron to palladium in the key transmetalation step. Specifically, these studies establish the identity of two different intermediates containing Pd-O-B linkages, a tri-coordinate (6-B-3) boronic acid complex and a tetra-coordinate (8-B-4) boronate complex, both of which undergo transmetalation leading to the cross-coupling product. Two distinct mechanistic pathways have been elucidated for stoichiometric reactions of these complexes: (1) transmetalation via an unactivated 6-B-3 intermediate that dominates in the presence of an excess of ligand, and (2) transmetalation via an activated 8-B-4 intermediate that takes place with a deficiency of ligand.

Mechanistic Exploration of the Transmetalation and Reductive Elimination Events Involving PdIV–Abnormal NHC Complexes in Suzuki–Miyaura Coupling Reactions: A DFT Study

“…In the alternative route 4 A , 2 A first undergoes a water expulsion reaction, which leads to intermediate 10 A via [2 A ‐10 A ] ≠ (Figure a). A similar water removal step was demonstrated by Thomas and Denmark during the characterization of different Pd‐O‐B‐containing pre‐transmetalation complexes . The activation barrier associated with the step 2 A → 10 A (Δ ≠ G L S‐D3 =31.4 kcal mol −1 ) is higher than that calculated for 2 A → 7 A by 2.7 kcal mol −1 (Figure a).…”

“…In the following step, the crucial transmetalation of 10 A occurs to generate 7 A with simultaneous removal of the O=B(OMe) fragment, which readily oligomerizes to cyclic metaborate ester [OB(OMe)] 3 . The formation of the similar boroxine [OB(OH)] 3 during the transmetalation reaction of the arylpalladium(II) boronate complexes in Suzuki–Miyaura reactions has previously been reported and characterized . The B−O bonds in the ring framework of the planar trimethoxyboroxine ( VI ) have an average bond length of 1.379 Å, whereas the exocyclic B−O bonds are significantly shorter (1.352 Å).…”

DFT Investigation of Suzuki–Miyaura Reactions with Aryl Sulfamates Using a Dialkylbiarylphosphine-Ligated Palladium Catalyst

“…Recently, Denmark and co-workers have comprehensively explored transmetalation in Suzuki–Miyaura reactions. 23 They have shown that the generation of an activated boronate species may not be necessary for transmetalation to occur, with certain conditions allowing for transmetalation directly from the boronic acid. However, for our specific system, the pathway for transmetalation directly from the boronic acid is higher than that shown in Figure 7, meaning that formation of a more active boronate species is required (see the Supporting Information).…”

Exposing the Origins of Irreproducibility in Fluorine NMR Spectroscopy

“…[1] In particular,t he excellent sensitivity of fluorine nuclei and the advent of mild fluorination reagents and procedures [2] over the past decades have resulted in an exponential and interdisciplinary use of 19 FNMR spectroscopy spanning the fields of synthetic and medicinal chemistry, [3] drug screening, [4] and RNAa nd protein function analysis [5] (Figure 1). [1] In particular,t he excellent sensitivity of fluorine nuclei and the advent of mild fluorination reagents and procedures [2] over the past decades have resulted in an exponential and interdisciplinary use of 19 FNMR spectroscopy spanning the fields of synthetic and medicinal chemistry, [3] drug screening, [4] and RNAa nd protein function analysis [5] (Figure 1).…”