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

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

Elucidating the Role of the Boronic Esters in the Suzuki–Miyaura Reaction: Structural, Kinetic, and Computational Investigations

The Suzuki–Miyaura reaction is the most practiced palladium-catalyzed, cross-coupling reaction because of its broad applicability, low toxicity of the metal (B), and the wide variety of commercially available boron substrates. A wide variety of boronic acids and esters, each with different properties, have been developed for this process. Despite the popularity of the Suzuki–Miyaura reaction, the precise manner in which the organic fragment is transferred from boron to palladium has remained elusive for these reagents. Herein, we report the observation and characterization of pretransmetalation intermediates generated from a variety of commonly employed boronic esters. The ability to confirm the intermediacy of pretransmetalation intermediates provided the opportunity to clarify mechanistic aspects of the transfer of the organic moiety from boron to palladium in the key transmetalation step. A series of structural, kinetic, and computational investigations revealed that boronic esters can transmetalate directly without prior hydrolysis. Furthermore, depending on the boronic ester employed, significant rate enhancements for the transfer of the B-aryl groups were observed. Overall, two critical features were identified that enable the transfer of the organic fragment from boron to palladium: (1) the ability to create an empty coordination site on the palladium atom and (2) the nucleophilic character of the <i>ipso</i> carbon bound to boron. Both of these features ultimately relate to the electron density of the oxygen atoms in the boronic ester

Rapid Injection NMR Reveals η³ ‘π-Allyl’ Cu^III Intermediates in Addition Reactions of Organocuprate Reagents

By using rapid injection NMR, it has now been possible to prepare and characterize the η³ ‘π-allyl’ copper­(III) intermediate that has been proposed for addition reactions of organocopper­(I) reagents and α,β-unsaturated carbonyl compounds

Complexes of the Gilman Reagent with Double Bonds across the π–σ Continuum

By using rapid injection NMR at low temperatures, a variety of π-complexes of lithium dimethylcuprate­(I) with C–C, C–N, and C–S double bonds have been prepared and characterized. Complexation is generally accompanied by large upfield changes in chemical shift for the substrate carbon atoms bonded to copper. In the case of α,β-unsaturated carbonyl compounds, the changes for the carbonyl carbons are much smaller in magnitude, which is consistent with the usual η² representation of these structures. It is possible for one ligand to displace another, and in this way an order of stability can be elucidated. Treatment of selected π-complexes with chlorosilanes or cyanosilanes gives Cu^III intermediates

ExCage

Cyclophanes, especially those where pyridinium units in conjugation with each other are linked up face-to-face within platforms that are held approximately 7 Å apart by rigid linkers, are capable of forming inclusion complexes with polycyclic aromatic hydrocarbons (PAHs) with high binding affinities as a result of a combination of noncovalent bonding interactions, including face-to-face [π···π] stacking and orthogonal [C–H···π] interactions. Here, we report the template-directed, catalyst-assisted synthesis of a three-fold symmetric, extended pyridinium-based, cage-like host (<b>ExCage</b>⁶⁺) containing a total of six π-electron-deficient pyridinium units connected in a pairwise fashion by three bridging <i>p</i>-xylylene linkers, displayed in a trigonal (1,3,5) fashion around two opposing and parallel 1,3,5-tris­(4‑pyridinium)­benzene platforms. The association constants (<i>K</i>_a) of eight complexes have been measured by isothermal titration calorimetry (ITC) in acetonitrile and were found to span the range from 2.82 × 10³ for naphthalene up to 5.5 × 10⁶ M^–1 for perylene. The barriers to decomplexation, which were measured in DMF-<i>d</i>₇ for phenanthrene, pyrene, triphenylene, and coronene by dynamic ¹H NMR spectroscopy undergo significant stepwise increases from 11.8 → 13.6 → 15.5 → >18.7 kcal mol^–1, respectively, while complexation experiments using rapid injection ¹H NMR spectroscopy in DMF-<i>d</i>₇ at −55 °C revealed the barriers to complexation for pyrene and coronene to be 6.7 and >8 kcal mol^–1, respectively. The kinetic and thermodynamic data reveal that, in the case of <b>ExCage</b>⁶⁺, while the smaller PAHs form complexes faster than the larger ones, the larger PAHs form stronger complexes than the smaller ones. It is also worthy of note that, as the complexes become stronger in the case of the larger and larger PAHs, the Rebek 55% solution formula for molecular recognition in the liquid state becomes less and less relevant