James A. Golen

A Labile and Catalytically Active Imidazol‐2‐yl Fragment System

N-heterocyclic carbenes (NHCs) and their complexes are excellent catalysts for a broad array of organic transformations, where the NHC ligands impart useful electronic and steric properties to metal centers. In these systems, with commonly used ancilliary NHC ligands that are substituted at nitrogen atom(s) by alkyl, aryl, or other groups, all catalytic transformations take place at the metal center, which is stabilized and/or activated by the NHC ligand. However, transformations that may possibly involve both the metal center and at one ring nitrogen of the NHC ligand are much less common, 5c,e–g] and are limited to protic NHC complexes or their conjugated bases. Thus, the N H function of a protic NHC complex (A or D ; Scheme 1) could

Platinum-Catalyzed Enantioselective Tandem Alkylation/Arylation of Primary Phosphines. Asymmetric Synthesis of P-Stereogenic 1-Phosphaacenaphthenes

Enantioselective tandem alkylation/arylation of primary phosphines with 1-bromo-8-chloromethylnaphthalene catalyzed by Pt(DuPhos) complexes gave P-stereogenic 1-phosphaacenaphthenes (AcePhos) in up to 74% ee. Diastereoselective formation of four P-C bonds in one pot with bis(primary) phosphines gave C2-symmetric diphosphines, including the o-phenylene derivative DuAcePhos, for which the rac isomer was formed with high enantioselectivity. These reactions, which appear to proceed via an unusual metal-mediated nucleophilic aromatic substitution pathway, yield a new class of heterocycles with potential applications in asymmetric catalysis.

Enabling Bifunctionality and Hemilability of N‐Heteroaryl NHC Complexes

N-Heterocyclic carbene (NHC) complexes have been shown to be extremely versatile and stable catalysts for reactions as diverse as olefin metathesis, transfer hydrogenation, and C-C coupling reactions. NHCs are attractive ligACHTUNGTRENNUNGands due to their strong s-donating ability, poor back bondACHTUNGTRENNUNGing,[2a–h] and relative air, moisture, and thermal stability of their complexes. Electronic and steric optimization of the properties of NHC-metal complexes is possible through NHC ligand design. Further improvement of catalyst performance through NHC functionalization has been studied using a variety of pendant groups, including heterocycle, phosphine, amine, and imine donor functions. In many cases the added ligand creates a stable chelate or pincer, whereas in other cases a hemilabile system and its temporary ligand loss (as in 2) favor catalysis. In contrast, this paper introduces a fundamentally different approach, where a substituent on an NHC ligand will act as a hydrogen bond acceptor (3) or base (4), which could facilitate catalysis (Scheme 1). Some recent studies on NHC metal complexes have raised the possibility of pendant nitrogen involvement, though as far as we are aware, no direct evidence was presented in these studies. In particular, for 5 a, decoordination of the pyrimidine (cf. 1!2) would make a basic nitrogen available near the metal active site (cf. 2!3 or 4). However, the NMR spectrum of 5 a was reported to remain sharp even at 110 8C, suggesting that decoordination and rotation about the pyrimidine NHC bond is a process with a high activation barrier. Therefore, in order to fully realize the potential of NHC ligands with pendant heterocyclic bases their ability to chelate with a metal must be decreased (Scheme 1), and we hypothesized that this could be achieved by introducing a large substituent R. Here we report successful strategies toward achieving this aim, which should be of general application to NHC chemistry.

Hydrogen‐Bonding Pincer Complexes with Two Protic N‐Heterocyclic Carbenes from Direct Metalation of a 1,8‐Bis(imidazol‐1‐yl)carbazole by Platinum, Palladium, and Nickel

Pincer protic N-heterocyclic carbene (PNHC) complexes were synthesized by direct metalation, the formation of a metal carbon bond from an unfunctionalized CH bond in a single synthetic step. Significantly, direct metalation succeeded even for a first-row metal, nickel. The chloride complexes were isolated and then converted to the acetate, triflate, or in the platinum case, a hydride analogue. Crystal structures and (1) H, (13) C, and (15) N NMR data, as well as IR spectra, document the effects of intramolecular hydrogen bonding and the planar but flexible pincer framework. Anti-Markovnikov addition of OH bonds to alkynes, including catalyzed alkyne hydration, were demonstrated on the Pt triflate analog.

Isomeric Trimethylene and Ethylene Pendant-armed Cross-bridged Tetraazamacrocycles and in Vitro/in Vivo Comparisions of their Copper(II) Complexes

Ethylene cross-bridged tetraamine macrocycles are useful chelators in coordination, catalytic, medicinal, and radiopharmaceutical chemistry. Springborg and co-workers developed trimethylene cross-bridged analogues, although their pendant-armed derivatives received little attention. We report here the synthesis of a bis-carboxymethyl pendant-armed cyclen with a trimethylene cross-bridge (C3B-DO2A) and its isomeric ethylene-cross-bridged homocyclen ligand (CB-TR2A) as well as their copper(II) complexes. The in vitro and in vivo properties of these complexes are compared with respect to their potential application as 64Cu-radiopharmaceuticals in positron emission tomography (PET imaging). The inertness of Cu-C3B-DO2A to decomplexation is remarkable, exceeding that of Cu-CB-TE2A. Electrochemical reduction of Cu-CB-TR2A is quasi-reversible, whereas that of Cu-C3B-DO2A is irreversible. The reaction conditions for preparing 64Cu-C3B-DO2A (microwaving at high temperature) are relatively harsh compared to 64Cu-CB-TR2A (basic ethanol). The in vivo behavior of the 64Cu complexes was evaluated in normal rats. Rapid and continual clearance of 64Cu-CB-TR2A through the blood, liver, and kidneys suggests relatively good in vivo stability, albeit inferior to 64Cu-CB-TE2A. Although 64Cu-C3B-DO2A clears continually, the initial uptake is high and only about half is excreted within 22 h, suggesting poor stability and transchelation of 64Cu to proteins in the blood and/or liver. These data suggest that in vitro inertness of a chelator complex may not always be a good indicator of in vivo stability.

Structural and Electronic Properties of Old and New A2[M(pinF)2] Complexes

Seven new homoleptic complexes of the form A2[M(pin(F))2] have been synthesized with the dodecafluoropinacolate (pin(F))(2-) ligand, namely (Me4N)2[Fe(pin(F))2], 1; (Me4N)2[Co(pin(F))2], 2; ((n)Bu4N)2[Co(pin(F))2], 3; {K(DME)2}2[Ni(pin(F))2], 4; (Me4N)2[Ni(pin(F))2], 5; {K(DME)2}2[Cu(pin(F))2], 7; and (Me4N)2[Cu(pin(F))2], 8. In addition, the previously reported complexes K2[Cu(pin(F))2], 6, and K2[Zn(pin(F))2], 9, are characterized in much greater detail in this work. These nine compounds have been characterized by UV-vis spectroscopy, cyclic voltammetry, elemental analysis, and for paramagnetic compounds, Evans method magnetic susceptibility. Single-crystal X-ray crystallographic data were obtained for all complexes except 5. The crystallographic data show a square-planar geometry about the metal center in all Fe (1), Ni (4), and Cu (6, 7, 8) complexes independent of countercation. The Co species exhibit square-planar (3) or distorted square-planar geometries (2), and the Zn species (9) is tetrahedral. No evidence for solvent binding to any Cu or Zn complex was observed. Solvent binding in Ni can be tuned by the countercation, whereas in Co only strongly donating Lewis solvents bind independent of the countercation. Indirect evidence (diffuse reflectance spectra and conductivity data) suggest that 5 is not a square-planar compound, unlike 4 or the literature K2[Ni(pin(F))2]. Cyclic voltammetry studies reveal reversible redox couples for Ni(III)/Ni(II) in 5 and for Cu(III)/Cu(II) in 8 but quasi-reversible couples for the Fe(III)/Fe(II) couple in 1 and the Co(III)/Co(II) couple in 2. Perfluorination of the pinacolate ligand results in an increase in the central C-C bond length due to steric clashes between CF3 groups, relative to perhydropinacolate complexes. Both types of pinacolate complexes exhibit O-C-C-O torsion angles around 40°. Together, these data demonstrate that perfluorination of the pinacolate ligand makes possible highly unusual and coordinatively unsaturated high-spin metal centers with ready thermodynamic access to rare oxidation states such as Ni(III) and Cu(III).

Thiocyanate-Ligated Heterobimetallic {PtM} Lantern Complexes Including a Ferromagnetically Coupled 1D Coordination Polymer

A series of heterobimetallic lantern complexes with the central unit {PtM(SAc)4(NCS)} have been prepared and thoroughly characterized. The {Na(15C5)}[PtM(SAc)4(NCS)] series, 1 (Co), 2 (Ni), 3 (Zn), are discrete compounds in the solid state, whereas the {Na(12C4)2)}[PtM(SAc)4(NCS)] series, 4 (Co), 5 (Ni), 6 (Zn), and 7 (Mn), are ion-separated species. Compound 7 is the first {PtMn} lantern of any bridging ligand (carboxylate, amide, etc.). Monomeric 1-7 have M(2+), necessitating counter cations that have been prepared as {(15C5)Na}(+) and {(12C4)2Na}(+) variants, none of which form extended structures. In contrast, neutral [PtCr(tba)4(NCS)]∞ 8 forms a coordination polymer of {PtCr}(+) units linked by (NCS)(-) in a zigzag chain. All eight compounds have been thoroughly characterized and analyzed in comparison to a previously reported family of compounds. Crystal structures are presented for compounds 1-6 and 8, and solution magnetic susceptibility measurements are presented for compounds 1, 2, 4, 5, and 7. Further structural analysis of dimerized {PtM} units reinforces the empirical observation that greater charge density along the Pt-M vector leads to more Pt···Pt interactions in the solid state. Four structural classes, one new, of {MPt}···{PtM} units are presented. Solid state magnetic characterization of 8 reveals a ferromagnetic interaction in the {PtCr(NCS)} chain between the Cr centers of J/kB = 1.7(4) K.

Mild, green copper/4-dimethylaminopyridine catalysed aerobic oxidation of alcohols mediated by nitroxyl radicals in water

A novel copper/4-dimethylaminopyridine catalyst system has been found to catalyse the aerobic oxidation of a variety of primary and secondary alcohols in water at room temperature, in the presence of a TEMPO or ABNO nitroxyl radical. A tetranuclear CuII cluster was revealed to be a plausible reactive intermediate.

Synthesis and Characterization of Bismuth(III) and Antimony(III) Calixarene Complexes

A series of calixarene bismuth and antimony complexes have been fully characterized by NMR, X-ray, IR, UV/vis, and elemental analysis. The reactions of SbCl(3) with the monosodium salt of p-tert-butylcalix[4]arene (Bu(t)C4), Bu(t)C4.Na, and the tetralithium salt of para-tert-butylcalix[4]arene, Bu(t)C4.Li(4), afforded two diantimony calix[4]arene complexes Bu(t)C4(SbCl)(2), with different (1)H NMR spectra and different THF coordination, but the same core structures. Other calix[4]arene antimony complexes (HC4(SbCl)(2) 2 and AC4(SbCl)(2) 3, diantimony chloride complexes of calix[4]arene and p-allylcalix[4]arene) and calix[4]arene bismuth complexes (Bu(t)C4(BiCl(2))(2)Li(2) 4, HC4(BiCl(2))(2)Li(2).6DMSO 5, and AC4(BiCl(2))(2)Li(2).4THF 6) were prepared by the reactions of MCl(3) (M = Sb or Bi) with RC4.Li(4) (R = Bu(t), H, or allyl) in a 2:1 molar ratio in THF. The same strategy was applied for Bu(t)C8 (p-tert-butylcalix[8]arene), and the desired bismuth complex [Bu(t)C8(BiCl(2))(4)(mu-Cl)(2)Li(6)][4THF.7DME] 12 was successfully synthesized. Complex 12 contains a planar Bi(4) core with four terminal chlorine atoms, which adopt a syn arrangement with respect to the plane defined by four bismuth atoms, and orient away from each other. A calix[4]arene monobismuth complex 11 was prepared by the reaction of Bi(OBu(t))(3) with the 1,2-disubstituted benzyl ether of calix[4]arene. Complexes 1-6 contain central planar M(2)(mu-O)(2) (M = Sb or Bi) four-membered rings, similar to four-membered rings observed in other calix[4]arene main group metal complexes. Intramolecular bismuth-arene pi interactions are observed in complexes 4-6 and 11 but not 12.

Diverse zinc(II) coordination assemblies built on divergent 4,2′:6′,4′′-terpyridine derivatives: syntheses, structures and catalytic properties

A series of metal–organic architectures (compounds 1–5) based on zinc salts and four 4′-substituted 4,2′:6′,4′′-tpys including two new ligands have been synthesized and structurally characterized. The ligands L1–L4 with various 4′-substituents on 4,2′:6′,4′′-tpy react with Zn(OAc)2·2H2O to yield assemblies 1–4 containing either 1-D polymeric chains (1–3) or a discrete dinuclear complex (4). X-ray structural analysis revealed that although similar 1-D polymeric chains were observed in both 1 and 3, the 3-D packing modes were essentially different. The chains in 1 were stacked to form a network structure with microporous channels that were not present in 3. In contrast, 4 was a discrete dinuclear complex containing a paddle-wheel {Zn2(μ-OAc)4} motif, although another minor component possibly coexists in the bulk sample as revealed by the PXRD studies. Crystals of 5 were prepared from the reaction between L4 and ZnI2 and its X-ray structure revealed a 1-D polymeric chain with a wave-like structure. Phase-pure compounds 1–3 and 5 were tested for the catalytic transesterification of phenyl acetate with alcohols, and the results indicated that 1 was the most active catalyst for this reaction, affording the new ester product in 95% yield at 50 °C under neat conditions, while other catalysts also catalysed the reaction with modest yields. Several different alcohols were examined as substrates for 1-catalysed transesterification and it was found that the size of substrates has important influence on the catalytic efficiency. In addition, amine additives were found to remarkably promote the catalytic efficiency of the less active catalyst 3. The structure–catalytic activity relationship was discussed in detail based on the catalytic data obtained.