Aryl chlorides biologically active

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

Examples of biologically active aryl chlorides— the drugs bupropion and chlorpheniramine, and 2,4-D and 2,4,5-T, herbicide components of the defohant Agent Orange (Section 18.3)... 

Alkenyl, Alkynyl, Aryl and Related Acids. Vinylphosphonates are an important group of compounds that have found use in organic transformations. They are also useful reagents for the synthesis of biologically active systems. The synthesis of vinylphosphonates is varied. However additional convenient routes to them are always welcome. Four recent reports demonstrated that zirco-nacycles (180), readily available from diethyl 1-alkynylphosphonates, are very useful precursors of different vinylphosphonates. They react with alkynes, aldehydes, ketones acyl chlorides and nitriles to produce, in a highly stereo- and regio-selective manner, substituted vinylphosphonates (181), (182), (183) (184) and (185) respectively (Scheme 46). 

Besides the electron-withdrawing substituent activated aryl chlorides, heteroaryl chlorides are another family of activated chlorides that also holds interesting biological activities. Under this background, there are many procedures that have been developed for the carbonylative transformation of heteroaryl chlorides. In general, the reaction conditions for these methodologies are much milder. 

Diaryliodonium salts are industrially employed as photoinitiators in cationic polymerizations [8-10]. They have been employed as Lewis acids [11], as oxidants (via formation of phenyl radicals) [12, 13], and in the area of macromolecular chemistry [14, 15]. Furthermore, diaryliodonium salts show biological activity in various applications, usually because of their ability to act as radical initiators [3, 16]. Diphenyleneiodonium chloride (DPI) is a cyclic diaryliodonium salt which has found numerous biological applications, often as a NADPH oxidase inhibitor ([17] see also [20 0] in [18]). The applications outlined above do not involve arylations and are hence not covered in this chapter. 

The coupling of iodo aryls with various olefins was conducted in the presence of palladium chloride (2.0 mol%) at ambient temperature under ultrasonic irradiation in water with yields between 43 and 90% [154], In situ formation of palladium nanoparticles was confirmed by transmission electron microscope and X-ray diffraction analyses, and the palladium nanoparticles could be reused for multiple reactions without significant loss of activity. Biologically relevant stilbene derivates, such as resveratrol, piceatannol and pinosilvine, were efficiently prepared with high regioselectivity and complete stereocontrol (TONS up to 10 , 0.01 to 0.50 mol% catalyst) [148], The activity of the oxime-derived palladacycle catalysts was compared in neat water with a DMF-water mixture, with similar... 

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