A Modular Approach to Structurally Diverse Bidentate Chelate Ligands for Transition Metal Catalysis

Abstract

A modular approach to a new class of structurally diverse bidentate P/N, P/P, P/S, and P/Se chelate ligands has been developed. Starting from hydroquinone, various ligands were synthesized in a divergent manner via orthogonally bis-protected bromohydroquinones as the central building block. The first donor functionality (L1) is introduced to the aromatic (hydroquinone) ligand backbone either by Pd-catalyzed cross-coupling (Suzuki coupling) with hetero-aryl bromides, by Pd-catalyzed amination, or by lithiation and subsequent treatment with electrophiles (e.g., chlorophosphanes, disulfides, diselenides, or carbamoyl chlorides). After selective deprotection, the second ligand tooth (L2) is attached by reaction of the phenolic OH functionality with a chlorophosphane, a chlorophosphite, or a related reagent. Some of the resulting chelate ligands were converted into the respective PdX2 complexes (X = Cl, I), two of which were characterized by X-ray crystallography. The methodology developed opens an access to a broad variety of new chiral and achiral transition metal complexes and is generally suited for the solid-phase synthesis of combinatorial libraries, as will be reported separately.

Current methods for the synthesis of 2-substituted azoles

“…165 Bromothiazole 89 is a common 2-haloazole for Suzuki coupling reactions (Scheme 82). [166][167][168] Chemoselective reaction 169 of 2,4-dibromothiazole 101 proceeds selectively at C2 (Scheme 83), as does the 2-bromo-5-chloro derivative 179 (Scheme 84). 170 The first report of an arylated tetrazole formed via the Suzuki coupling 171 has been reported by Yi (Scheme 85), as well as a novel coupling of thioethers of oxazole, thiazole and tetrazole with boronic acids was reported by Liebeskind.…”

Solid-Phase Development of Chiral Phosphoramidite Ligands for Enantioselective Conjugate Addition Reactions

“…The residue was purified by flash chromatography on silica gel (n-hexane/ethyl acetate 3:1, 1 % acetic acid) to yield an oil (309 mg, 0.563 mmol, 69 % CH 2 (CH 2 ) 2 COOH, CH 2 (CH 2 ) 3 COOH), 1.45 (s,9 H;(CH 3 ) 3 C); 13 C NMR (CDCl 3 , 100.6 MHz, mixture of diastereomers): d 178.6 (COOH), 155. 8,155.3,155.0 (CO urethane),144.8,144.2,141.6,141.4 (quart.,Fmoc),127.8,127.7,127.3,125.6,125.3,, 79.9 (C(CH 3 ) 3 ), 67.7 (Fmoc-CH 2 ), 50.9, 50.8 (CH 2 NBoc), 47.5 (Fmoc-CH), 43.3, 42.3 (CH 2 NFmoc), 38.3 (CHCH 2 N), 34.1 (CH 2 COOH), 31.8 (CH 2 (CH 2 ) 4 COOH), 30.3 (CH 2 (CH 2 ) 3 COOH), 28.6 ((CH 3 ) 3 C), 26.5 (CH 2 (CH 2 ) 2 COOH), 25.0 (CH 2 CH 2 COOH); IR (KBr): n Ä 2866 (Bohlmann-band), [29] 1708 cm À1 Coupling of ligand precursors to the solid phase a) Boc-oxa-bispidine system 9: A solution of 0.645 mmol),N,0.859 mmol) and DMAP (10 mg, 0.082 mmol) in CH 2 Cl 2 (8 mL) was added to hydroxymethylpolystyrene (495 mg, 0.87 mmol g À1 , 0.431 mmol) in a syringe reactor. The reactor was shaken overnight, and the resin was washed with CH 2 Cl 2 (3 Â ) and dried in vacuo.…”

A Novel Concept in Combinatorial Chemistry in Solution with the Advantages of Solid-Phase Synthesis: Formation of N-Betaines by Multicomponent Domino Reactions

“…[2] Among the biological phenomena studied so far at single cells or substructures of single cells are individual exocytosis events, [3] oxygen consumption, [4] photosynthetic activity, [5] and ion channel distribution. [6] In these experiments, the electrochemical sensorÐ usually a microdisk electrode with a tip diameter of a few micrometersÐhas to be positioned in close proximity to the object.…”

“…The tip is then retracted for a defined distance allowing, in principal, adjustment of the membrane-to-electrode distance within a range of several hundred nanometers to two micrometers. Although this approach has been successfully used in recent years, [3] there are significant drawbacks, such as a) possible contamination of the electrode surface due to its contact with the cell membrane, b) insufficient reproducibility of the tip-to-cell distance, which becomes even more difficult using smaller microelectrodes, that are hardly visible in the optical microscope, c) eventual deterioration of the cell at the contact point or mechanical depolarization of the cell, and d) the impossibility to investigate sequentially different spots on the same cell.…”

“…A Novel Concept in Combinatorial Chemistry in Solution with the Advantages of Solid-Phase Synthesis: Formation of N-Betaines by Multicomponent Domino Reactions** Lutz F. Tietze,* Holger Evers, and Enno Töpken Dedicated to Professor Ivar Ugi on the occasion of his 70th birthday Combinatorial chemistry is an important method, both in the search for lead structures of pharmacologically active compounds and in their optimization, [1] and it also finds application in supramolecular chemistry, [2] in catalyst development, [3] and in material science. [4] Within this context combinatorial solid-phase synthesis [5] has the advantage of simple automation, since reagents can be used in excess, and impurities and by-products can be removed by simple filtration and washing procedures.…”