Mechanistic Studies on the Insertion of Carbonyl Substrates into Cu-H: Different Rate-Limiting Steps as a Function of Electrophilicity.

We report mechanistic studies on the insertion reactions of [(NHC)Cu(µ-H)]2 complexes with carbonyl substrates by UV-vis and 1 H NMR spectroscopic kinetic studies, H/D isotopic labelling, and X-ray crystallography. The results of these comprehensive studies show that the insertion of Cu-H with an aldehyde, ketone, activated ester/amide, and unactivated amide consist of two different rate limiting steps: the formation of Cu-H monomer from Cu-H dimer for more electrophilic substrates, and hydride transfer from a transient Cu-H monomer for less electrophilic substrates. We also report spectroscopic and crystallographic characterization of rare Cu-hemiacetalate and Cu-hemiaminalate moieties from the insertion of an ester or amide into the Cu-H bond.

Copper-Oxygen Complexes Revisited: Structures, Spectroscopy, and Reactivity.

A longstanding research goal has been to understand the nature and role of copper-oxygen intermediates within copper-containing enzymes and abiological catalysts. Synthetic chemistry has played a pivotal role in highlighting the viability of proposed intermediates and expanding the library of known copper-oxygen cores. In addition to the number of new complexes that have been synthesized since the previous reviews on this topic in this journal (Mirica, L. M.; Ottenwaelder, X.; Stack, T. D. P. Chem. Rev. 2004, 104, 1013-1046 and Lewis, E. A.; Tolman, W. B. Chem. Rev. 2004, 104, 1047-1076), the field has seen significant expansion in the (1) range of cores synthesized and characterized, (2) amount of mechanistic work performed, particularly in the area of organic substrate oxidation, and (3) use of computational methods for both the corroboration and prediction of proposed intermediates. The scope of this review has been limited to well-characterized examples of copper-oxygen species but seeks to provide a thorough picture of the spectroscopic characteristics and reactivity trends of the copper-oxygen cores discussed.

Copper Complexes of Multidentate Carboxamide Ligands.

The copper coordination chemistry of two multidentate carboxamido ligands derived from HL1 (offering two quinolyl and one carboxamide donor) and H4L2 (with two pyridine(dicarboxamido) units linked by naphthalene spacers) was explored. The former was chosen because upon deprotonation it would provide a monoanionic mer-coordinating N-donor set that would model the putative deprotonated form of the His-brace in copper monooxygenases, while the latter was designed to bind two copper ions and enable comparisons to other systems with different ligand spacers. Upon reaction with Cu(I)-mesityl, HL1 yielded a symmetric dimer (L1Cu)2 in which each bis(quinolyl)amide ligand binds via two N-donors to one Cu(I) ion and via the third to the other Cu(I) center. Monomeric Cu(II) complexes [L 1 Cu(H 2 O) 2 ](OTf) and L 1 2 Cu were also characterized. Treatment of H4L2 with Cu(OTf)2 and excess Me4NOH (in CH3CN, pyridine/H2O, or MeOH) yielded complexes with anions of general formula [L 2 Cu 2 (X)]n-, where X = CH3CONH- (n = 1), CO3 2- (n = 2), or MeO- (n = 1). X-ray structures of these complexes revealed the (L2)4- ligand binding to two Cu(II) ions in an open paddle-wheel geometry, with an additional bridging ligand (X) completing the square planar coordination sphere of each metal ion. The open paddlewheel motif differs from the more 'open' puckered geometry seen with related ligands with different spacer units.

Sterically Induced Ligand Framework Distortion Effects on Catalytic Cyclic Ester Polymerizations.

Aluminum alkoxide complexes supported by salen ligands [salen = N, N'-bis(salicylaldimine)-2-methylpropane-1,2-diamine or N, N'-bis(salicylaldimine)-2,2-dimethylpropane-1,3-diamine] with o-adamantyl substituents have been synthesized and investigated for the polymerization of ε-caprolactone. Geometric analysis of the catalysts used for the reaction reveals the metal coordination geometries to be intermediate between square-pyramidal and trigonal-bipyramidal. A detailed kinetic study accompanied by density functional theory modeling of key mechanistic steps of the reaction suggest that, in addition to the length of the backbone linker, the o-aryl substituents have a significant impact on the catalyst's reactivity. Bulky ortho substituents favorably distort the precatalyst geometry and thereby foster the achievement of the rate-limiting transition-state geometry at low energetic cost, thus accelerating the reaction.

Formally Copper(III)-Alkylperoxo Complexes as Models of Possible Intermediates in Monooxygenase Enzymes.

Reaction of [NBu4][LCuIIOH] with excess ROOH (R = cumyl or tBu) yielded [NBu4][LCuIIOOR], the reversible one-electron oxidation of which generated novel species with [CuOOR]2+ cores (formally CuIIIOOR), identified by spectroscopy and theory for the case R = cumyl. This species reacts with weak O-H bonds in TEMPO-H and 4-dimethylaminophenol (NMe2PhOH), the latter yielding LCu(OPhNMe2), which was also prepared independently. With the identification of [CuOOR]2+ complexes, the first precedent for this core in enzymes is provided, with implications for copper monooxygenase mechanisms.

Why So Slow? Mechanistic Insights from Studies of a Poor Catalyst for Polymerization of ε-Caprolactone.

Polymerization of ε-caprolactone (CL) using an aluminum alkoxide catalyst (1) designed to prevent unproductive trans binding was monitored at 110 °C in toluene-d8 by 1H NMR and the concentration versus time data fit to a first-order rate expression. A comparison of t1/2 for 1 to values for many other aluminum alkyl and alkoxide complexes shows much lower activity of 1 toward polymerization of CL. Density functional theory calculations were used to understand the basis for the slow kinetics. The optimized geometry of the ligand framework of 1 was found indeed to make CL trans binding difficult: no trans-bound intermediate could be identified as a local minimum. Nor were local minima for cis-bound precomplexes found, suggesting a concerted coordination-insertion for polymer initiation and propagation. The sluggish performance of 1 is attributed to a high-framework distortion energy required to deform the "resting" ligand geometry to that providing optimal catalysis in the corresponding transition-state structure geometry, thus suggesting a need to incorporate ligand flexibility in the design of efficient polymerization catalysts.

Mechanism of the Polymerization of rac-Lactide by Fast Zinc Alkoxide Catalysts.

The ring-opening transesterification polymerization (ROTEP) of rac-lactide (rac-LA) using LXZn catalysts (LX = ligand having phenolate, amine, and pyridine donors with variable para substituents X on the bound phenolate donor; X = NO2, Br, t-Bu, OMe) was evaluated through kinetics experiments and density functional theory, with the aim of determining how electronic modulation of the ligand framework influences polymerization rate, selectivity, and control. After determination that zinc-ethyl precatalysts required 24 h of reaction with benzyl alcohol to convert to active alkoxide complexes, the subsequently formed species proved to be active and fairly selective, polymerizing up to 300 equiv of rac-LA in 6-10 min while yielding isotactic (Pm = 0.72-0.78) polylactide (PLA) with low dispersities: D = 1.06-1.17. In contrast to previous work with aluminum catalysts for which electronic effects of ligand substituents were significant (Hammett ρ = +1.2-1.4), the LXZn systems exhibited much less of an effect (ρ = +0.3). Density functional calculations revealed details of the initiation and propagation steps, enabling insights into the high isotacticity and the insensitivity of the rate on the identity of X.

Secondary Sphere Hydrogen Bonding in Monocopper Complexes of Potentially Dinucleating Bis(carboxamide) Ligands.

Reaction of a macrocyclic ligand precursor comprising two bis(carboxamido)pyridine units (H4L4) connected by ethylene linkers with NMe4OH and CuX2 (X = Cl, OAc, or OTf) yielded monocopper complexes [NMe4][(H2L4)Cu(X)] (X = Cl (3), OAc (4), or OH (5)), in contrast to previous work using a related ligand with ortho-phenylene linkers wherein dicopper compounds were isolated. X-ray structures of the complexes revealed hydrogen bonding from the free carboxamide N-H groups in the doubly protonated form of the ligand (H2L4- ) to the monodentate fourth ligand coordinated to the Cu(II) ion. Similar secondary sphere hydrogen bonding interactions were identified in multinuclear compounds [NMe4]2[((H2L4)Cu)n(CO3)] (n = 2 or 3) that were isolated from exposure of 5 to air. Cyclic voltammetry revealed oxidations of 3 and 5 at potentials ~300 mV higher than analogous monocopper complexes of bis(arylcarboxamido)pyridine ligands which lack the intramolecular hydrogen bonds, consistent with removal of electron density from the metal center by the hydrogen bonding array. Another ligand variant (H4L5) with ortho-phenylene linkers and only one bis(carboxamido)pyridine moiety yielded monocopper complexes [NMe4][(H2L5)Cu(OAc)] • DMF (8) and [NMe4][(H2L5)CuCl)] • CH3CN (9), but the X-ray structures revealed a different hydrogen bonding arrangement to the solvate molecules. Nonetheless, a high redox potential for 9 was observed, consistent with intramolecular hydrogen bonding interactions in solution.

Mechanistic Studies of ε-Caprolactone Polymerization by (salen)AlOR Complexes and a Predictive Model for Cyclic Ester Polymerizations.

Aluminum alkoxide complexes (2) of salen ligands with a three-carbon linker and para substituents having variable electron-withdrawing capabilities (X = NO2, Br, OMe) were prepared, and the kinetics of their ring-opening polymerization (ROP) of ε-caprolactone (CL) were investigated as a function of temperature, with the aim of drawing comparisons to similar systems with two-carbon linkers investigated previously (1). While 1 and 2 exhibit saturation kinetics and similar dependences of their ROP rates on substituents X (invariant Keq, similar Hammett ρ = +1.4(1) and 1.2(1) for k2, respectively), ROP by 2 was significantly faster than for 1. Theoretical calculations confirm that, while the reactant structures differ, the transition state geometries are quite similar, and by analyzing the energetics of the involved distortions accompanying the structural changes, a significant contribution to the basis for the rate differences was identified. Using this knowledge, a simplified computational method for evaluating ligand structural influences on cyclic ester ROP rates is proposed that may have utility for future catalyst design.