Oxidative homologation, method

If, however, PEG-400 is employed as the solvent and phase transfer catalyst, under a nitrogen atmosphere, then the monoacid is obtained in good yield. Since vinylic dibromides are easily synthesized from carbonyl compounds, this constitutes a valuable method for oxidative homologation(19). 

A one-carbon homologation method for converting various aldehydes and ketones (110) into a-halo-esters (112) (Scheme 8) consists of sequential Knoevenagel condensation with malononitrile and oxidation (NaCIO) to give epoxide (111) followed by treatment with HX-EtOH... 

A variety of methods have been put forward for functionalizing pyridines. Sukbok Chang of KAIST described J. Am. Chem. Soc. 2008, 130, 9254) the direct oxidative homologation of a pyridine A-oxide 16 to give the unsaturated ester 18. Jonathan Clay den of the University of Manchester observed (Organic Lett. 2008,10, 3567) that metalation of 19 gave an anion that rearranged to 20 with complete retention of enantiomeric excess. 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

A two-step procedure was required for the preparation of a diverse set of pyrrole-3-carboxylic acid derivatives. The diketone 15 was prepared using a functional homologation of a 6-ketoester 14 with different aldehydes followed by oxidation with PCC. The Paal-Knorr reaction was carried out in AcOH in a sealed tube under microwave irradiation (180 °C, 5-10 min) to give differently substituted pyrroles with a COOMe group in position 3 (Scheme 5). This group was further transformed to expand the diversity of the products prepared with this method [32]. 

The Kojima-Sakai approach, which makes use of trans-cis diester 626, is summarized in Scheme LVII This intermediate was homologated by the Arndt-Eistert method, converted to olefin 627, and oxidatively cleaved to produce ultimately the diester 628. Dieckmann condensation was used to construct the diquinane core which was subsequently transformed to 623 by standard reactions. 

Cyclization of nitro-stabilized radicals provides another method for the generation of cyclic nitronates (221). Oxidation of the aci-foim of nitroalkanes with ceric ammonium nitrate generates the ot-carbon centered radical, which in the presence of an alkene, leads to the homologation of the a-radical. In the case of a tethered alkene of appropriate length, radical addition leads to a cyclic nitronate (Scheme 2.20). 

This homologous Baeyer-Villiger type oxidative ring expansion represents a conceptually new protocol illustrating the substantial value of one-pot, four-component annulations as a flexible and simple new synthetic method. 

Of the 15 experimentally known phases of the higher oxides only five of them have been determined by X-ray and neutron diffraction using the Rietveld refinements method. To understand the thermodynamic behavior and phase reactions it is helpful to have a model of the undetermined structures. Using the experimental electron diffraction data it is possible to determine the symmetry of the unit cell and develops a transformation matrix between the fluorite and ten of the intermediate phases as shown in Table 2. The module theory provides a method for modeling the unknown structures of the homologous series of the lanthanide... 

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