A Highly Efficient Palladium(II)/Polyoxometalate Catalyst System for Aerobic Oxidation of Alcohols

A simple catalyst system composed of Pd(OAc)2, phosphomolybdic acid and tetrabutylammonium acetate oxidises a range of alcohols efficiently, with turnover numbers (TONs) of up to 10 000.</p

<em>N,O</em>-Ligated Pd(_II) Complexes for Catalytic Alcohol Oxidation

N,O-ligated Pd(II) complexes show considerable promise for the oxidation of challenging secondary aliphatic alcohols. The crystal structures of the highly active complexes containing the 8-hydroxyquinoline-2-carboxylic acid (HCA) and 8-hydroxyquinoline-2-sulfonic acid (HSA) ligands have been obtained. The (HSA) Pd(OAc)(2) system can effectively oxidise a range of secondary alcohols, including unactivated alcohols, within 4-6 h using loadings of 0.5 mol%, while lower loadings (0.2 mol%) can be employed with extended reaction times. The influence of reaction conditions on catalyst degradation was also examined in these studies

The synthesis of N-heterocycles via copper/TEMPO catalysed aerobic oxidation of amino alcohols

N-Heterocycles can be prepared using alcohol oxidation as a key synthetic step. Herein we report studies exploring the potential of Cu/TEMPO as an aerobic oxidation catalyst for the synthesis of substituted indoles and quinolines. Graphical abstract: The synthesis of N-heterocycles via copper/TEMPO catalysed aerobic oxidation of amino alcohols N-Heterocycles are important scaffolds for many drugs and natural products, and substituted quinolines and indoles are the basis of many top selling pharmaceuticals; for example, Singulair® and Maxalt®. The synthesis of such substituted N-heterocycles can be challenging with many traditional approaches requiring harsh conditions and delivering poor selectivity. An attractive route for the synthesis of N-heterocycles is to utilize alcohols as substrates as they are readily available and easy to handle. There are numerous examples where catalytic transfer hydrogenations or “hydrogen borrowing” methods have been used to prepare N-heterocycles from alcohols. A particularly desirable route for the selective synthesis of substituted N-heterocycles is the intramolecular oxidative cyclization of amino alcohols. Watanabe and co-workers previously employed this route for the synthesis of indoles, using a RuCl2(PPh3)3catalyst. More recently, heterogeneous ruthenium catalysts (Ru/CeO2 and Ru/ZrO2) were used to prepare indole using the same route. Fujita et al. reported the use of a [Cp*IrCl2]2catalyst for the synthesis of indoles, 1,2,3,4-tetrahydroquinolines and 2,3,4,5-tetrahydro-1-benzazepine. For the same starting materials, it was found that when the catalyst was switched to [Cp*RhCl2]2 it produced the corresponding five-, six-, and seven-membered ring lactams. This approach would be greatly improved if we could move away from expensive precious metals and employ more earth abundant metals. Given that oxidation of an alcohol to an aldehyde is the key step in this route, the Cu/TEMPO/O2 system is an attractive alternative.9 This biomimetic system employs a Cu(ii) or Cu(i)9e salt complexed by a ligand such as 2,2-bipyridine, the stable free radical TEMPO (2,2,6,6-tetramethylpiperidinyloxyl), a base and dioxygen as the terminal oxidant. Along with the fact that it employs copper, this system was appealing because it is known to operate under mild conditions and is selective for the oxidation of primary alcohols to aldehydes.9 This feature would increase the scope of this oxidative intramolecular oxidative cyclization and allow us to prepare N-heterocycles using substrates containing secondary alcohol functionality. Furthermore, because it is an aerobic approach we envisaged that this would allow us to obtain quinolines as opposed to tetrahydroquinolines and lactams which were obtained using the Ir and Rh catalysts mentioned earlier. While there have been numerous studies exploring Cu/TEMPO for catalytic alcohol oxidation, these studies have primarily focused on simple model substrates; the catalyst had not been exploited for the synthesis of N-heterocycles

Design of Selective PAK1 Inhibitor G‑5555: Improving Properties by Employing an Unorthodox Low‑p<i>K</i>_a Polar Moiety

Signaling pathways intersecting with the p21-activated kinases (PAKs) play important roles in tumorigenesis and cancer progression. By recognizing that the limitations of FRAX1036 (<b>1</b>) were chiefly associated with the highly basic amine it contained, we devised a mitigation strategy to address several issues such as hERG activity. The 5-amino-1,3-dioxanyl moiety was identified as an effective means of reducing p<i>K</i>_a and logP simultaneously. When positioned properly within the scaffold, this group conferred several benefits including potency, pharmacokinetics, and selectivity. Mouse xenograft PK/PD studies were carried out using an advanced compound, G-5555 (<b>12</b>), derived from this approach. These studies concluded that dose-dependent pathway modulation was achievable and paves the way for further in vivo investigations of PAK1 function in cancer and other diseases

Search for the standard model Higgs boson at LEP

The four LEP Collaborations, ALEPH, DELPHI, L3 and OPAL, have collected a total of 2461 pb(-1) of e(+)e(-) collision data at centre-of-mass energies between 189 and 209 GeV. The data are used to search for the Standard Model Higgs boson. The search results of the four Collaborations are combined and examined in a likelihood test for their consistency with two hypotheses: the background hypothesis and the signal plus background hypothesis. The corresponding confidences have been computed as functions of the hypothetical Higgs boson mass. A lower bound of 114.4 GeV/c(2) is established, at the 95% confidence level, on the mass of the Standard Model Higgs boson. The LEP data are also used to set upper bounds on the HZZ coupling for various assumptions concerning the decay of the Higgs boson. (C) 2003 Elsevier B.V. All rights reserved