Richard Mynott

Elementary Steps of Gold Catalysis: NMR Spectroscopy Reveals the Highly Cationic Character of a "Gold Carbenoid"

What are you? Even though the metal-induced ring opening of 3,3-disubstituted cyclopropenes is known to serve as a genuine carbene generator, the use of Au(I) in this reaction leads to a reactive intermediate with highly cationic character. This result has important implications for gold catalysis in general, which in the past has been commonly attributed to the intervention of gold carbenes.

Indenylidene Complexes of Ruthenium: Optimized Synthesis, Structure Elucidation, and Performance as Catalysts for Olefin Metathesis—Application to the Synthesis of the ADE-Ring System of Nakadomarin A

An optimized and large scale adaptable synthesis of the ruthenium phenylindenylidene complex 3 is described which employs commercially available diphenyl propargyl alcohol 5 as a stable and convenient carbene source. Previous ambiguities as to the actual structure of the complex have been ruled out by a full analysis of its NMR spectra. A series of applications to ring closing metathesis (RCM) reactions shows that complex 3 is as good as or even superior to the classical Grubbs carbene 1 in terms of yield, reaction rate, and tolerance towards polar functional groups. Complex 3 turns out to be the catalyst of choice for the synthesis of the enantiopure core segment 77 of the marine alkaloid nakadomarin A 60 comprising the ADE rings of this target. Together with a series of other examples, this particular application illustrates that catalyst 3 is particularly well suited for the cyclization of medium-sized rings by RCM. Other key steps en route to nakadomarin A are a highly selective intramolecular Michael addition setting the quaternary center at the juncture of the A and D rings and a Takai-Nozaki olefination of aldehyde 73 with CH2I2, Ti(OiPr)4 and activated zinc dust.

Transition metal allyls : IV. The (η3-allyl)2M complexes of nickel, palladium and platinum: reaction with tertiary phosphines

Abstract A series of 1 : 1 adducts have been prepared by treating the bis-η3-allyl complexes of nickel, palladium and platinum with tertiary phosphines. Investigations of their structure in solution as well as in the crystal have shown that both 18-electron (η3-allyl)2ML complexes as well as 16-electron (η1-allyl)-(η3-allyl)ML complexes may be formed.

Supercritical carbon dioxide as solvent and temporary protecting group for rhodium-catalyzed hydroaminomethylation.

Supercritical carbon dioxide (scCO2) acts simultaneously as solvent and temporary protecting group during homogeneously rhodium-catalyzed hydroaminomethylation of ethyl methallylic amine. Cyclic amines are formed as the major products in scCO,, whereas the cyclic amide is formed preferentially in conventional solvents. Multinuclear high-pressure NMR spectroscopy revealed that this selectivity switch is mainly due to reversible formation of the carbamic acid in the solvent CO2, which reduces the tendency for intramolecular ring closure at the Rh-acyl intermediate. These results substantiate the general concept of using scCO2 as a protective medium for amines in homogeneous catalysis and demonstrate for the first time its application for selectivity control.

A correlation between 13C and 59Co NMR data and the catalytic activity of organocobalt complexes in the synthesis of pyridine derivatives

Abstract The correlation between the 13 C and 59 Co NMR spectra of substituted cyclopentadienylcobalt complexes and their catalytic properties in the synthesis of pyridine derivatives is examined. Since the correlations can be expressed as linear relationships, a direct screening of potential catalysts by NMR is possible.

Transition metal allyls ☆: III. The (η3-allyl)2M complexes of nickel, palladium and platinum: structural considerations

Abstract The structures of a series of (η 3 -allyl) 2 M complexes of nickel, palladium and platinum have been investigated with the help of 13 C NMR, 1 H NMR and Raman spectroscopy. The crystal structure of (η 3 -cyclooctatrienyl) 2 Ni has been determined by X-ray methods; the two nickel-bonded η 3 -allyl groups are mutually trans .

A Synthesis-Driven Structure Revision of Berkelic Acid Methyl Ester

Matrix metalloproteinases (MMPs) are a family of zinccontaining endopeptidases involved in homeostasis of the extracellular matrix. Abnormal activity of such enzymes is implicated in pathological processes that result in osteoarthritis, rheumathoid arthritis, and multiple sclerosis, and also plays a decisive role in tumor metastasis. Small-molecule inhibitors of the individual MMPs are therefore highly interesting as prospective complements to the current chemotherapeutic regimens used in clinical settings. A promising lead in this context is berkelic acid, which was isolated from a Penicillium species collected in the very hostile environment of Berkeley Pit Lake, a flooded former copper mine in Butte, Montana. This particular extremophile has adapted to the waters of this lake, which are highly acidic (pH 2.5) and contain a cocktail of heavy-metal salts in remarkably high concentrations. Bioassay-guided fractionation of the CHCl3 extracts of the fungus showed berkelic acid to be the major metabolite responsible for the pronounced inhibition of MMP-3 (GI50 = 1.87 mm). [3] Moreover, the compound exhibits selective and potent activity against the ovarian cancer cell line OVCAR-3 (GI50 = 91 nm). [3] As MMP-3 is upregulated in OVCAR-3 but not in other ovarian cancer cell lines, these preliminary activity and selectivity data are highly encouraging and suggest that berkelic acid and derivatives thereof deserve more intense scrutiny. 4] The remarkable structural attributes of berkelic acid add further to the appeal of this compound. It was assigned the constitution and relative configuration 1 (Scheme 1) mainly on the basis of NMR experiments. Recent model studies directed towards synthesizing berkelic acid appear to corroborate this proposed structure, even though they reached contradictory conclusions as to whether the acetalization that produces the conspicuous chromane spiroketal core is thermodynamically or kinetically controlled. We now report our own investigations on berkelic acid methyl ester (2) which not only resolve this open question but also suggest that the original structure assignment needs to be revised. Since the configuration at the lateral quaternary stereocenter C22 of berkelic acid is unknown, a convergent approach was adopted that should allow both possible isomers to be prepared by incorporating either enantiomer of synthon A at a late stage (Scheme 1). This route utilizes a Michael addition/spiroacetalization cascade intended to convert a linear precursor of type C into the tetracyclic core B of the target in one step. Compound C, in turn, should arise from an aldol condensation between the aromatic nucleus D and the polyketide segment E. The preparation of the required building block D (Scheme 2) commenced with the copper-catalyzed opening of (R)-(+)-2-pentyloxirane (> 99% ee) by the Grignard reagent derived from 3,5-bis(benzyloxy)-1-bromobenzene to give 3. Hydrogenolysis of the benzyl ethers followed by a regioselective Kolbe–Schmitt carboxylation of the resulting phenol 4 furnished acid 5, which was esterified by treatment with diazomethane prior to conversion into bis-TBS ether 8 by exhaustive silylation and selective mono-desilylation. Since the attempted direct formylation of this product was unrewarding, we chose to introduce the required formyl Scheme 1. Retrosynthetic analysis of the structure 1 attributed to berkelic acid.

A Practical NMR‐Based High‐Throughput Assay for Screening Enantioselective Catalysts and Biocatalysts

Two NMR-based approaches for high-throughput screening of enantioselective catalysts and biocatalysts are described. One version makes use of pseudo-enantiomers or pseudo-meso-compounds based on 13C-labeling. A throughput of at least 1400 ee determinations per day is possible by using an appropriate flow-through cell and an autosampler. The other approach is based on traditional diastereomer formation using a chiral reagent or complexing agent. The ee values are accurate to within ±2% and ±5% of the true values.

Developing potentially useful organometallic Lewis acid catalysts: (η-cyclopentadienyl)zirconium trichloride derivatives

Abstract The organometallic Lewis acid (η-cyclopentadienyl)zirconium trichloride ( 2 ) was obtained from bis(cyclopentadienyl)zirconium dichloride ( 1 ) and chlorine by means of a radical induced metal-Cp bond cleavage. Reaction of 2 with tetrahydrofuran gave the CpZrCl 3 -bis(tetrahydrofuran) adduct 3 ; treatment of either 2 or 3 with excess dimethylformamide furnished CpZrCl 3 (dmf) 2 ( 4 ). (η-Methylcyclopentadienyl)bis(tetrahydrofuran)zirconium trichloride ( 7 ) was prepared by treatment of ZrCl 4 (thf) 2 ( 6 ) with one molar equivalent of the (methylcyclopentadienyl)thallium reagent 5 . Complexes 3, 4 and 7 were characterized by X-ray diffraction studies and their dynamic NMR spectra were recorded. Complex 3 crystallizes in space group P 2 1 / n with cell parameters a 8.155(1), b 13.342(2), c 15.775(1) A, β 104.81(1)°, Z = 4, R = 0.041, R w = 0.056. CpZrCl 3 (dmf) 2 ( 4 ) crystallizes in space group P 2 1 / c with cell parameters a 7.790(1), b 15.445(2), c 13.893(1) A, β 93.94(1)°, Z = 4, R = 0.032, R w = 0.052. Complex 7 crystallizes in space group P 2 1 / n with cell parameters a 10.242(2), b 12.836(2). c 13.683(1) A, β106.37 (1)°, Z = 4, R = 0.037, R w = 0.039. The (cyclopentadienyl)bis(tetrahydrofuran)zirconium trichloride adduct 3 selectively catalyzed the Diels-Alder addition of 2,3-dimethylbutadiene and methacrolein at ambient temperature to give 1,3,4-trimethyl-3-cyclohexenyl-1-carbaldehyde ( 13 ). However, the CpZrCl 3 -Lewis acid catalyzed rearrangement of 13 to 1,3,4-trimethylbicyclo[2.2.1]heptan-2-one ( 14 ) does not take place at a significant rate until ca. 150°C.

Transition metal allyls. VI: The stoichiometric reaction of 1,3-dienes with ligand modified zerovalent-nickel systems

Abstract Butadiene and methyl substituted 1,3-dienes react with zerovalent-nickel-ligand complexes in a stoichiometric manner to give octadienediylnickel-ligand complexes. The structure, rearrangement and reactions with CO and P-donor ligands of these species have been studied with the help of 1 H and 13 C NMR spectroscopy. The results provide an insight into the mechanism of the nickel-catalysed cyclodimerization of 1,3-dienes.