Coupling chemistry

Modem cross coupling chemistry is heavily dominated by the use of palladium and nickel complexes as the catalysts, which show an impressively wide scope and an excellent compatibility with many functional groups.2 This favorable application profile usually overcompensates the disadvantages resulting from the high price of the palladium precursors, the concerns about the toxicity of nickel salts, the need for ancillary ligands to render the complexes sufficiently active and stable, and the extended reaction times that are necessary in certain cases. 

These processes have flourished, mainly due to their selectivity and versatility, to the point where cross-coupling chemistry is often the initial thinking of organic chemists in synthetic and retro-synthetic approaches [2]. In fact, nowadays it is difficult to find a contribution in fine chemical or natural product synthesis where these molecular assembly tools are not employed. This is often due to the simple preparation and handling of the reaction partners as well as their relative compatibility with several functional groups. 

The ideal ligand for the cross-coupling reactions should satisfy the requirements of all stages of the catalytic cycle. In practice this is unlikely, as these requirements are not parallel. A careful compromise between various factors is necessary for any particular realization of cross-coupling chemistry. The path of reasoning should be similar for both Pd- and Ni-catalyzed processes however, since very little information is available concerning Ni catalysis, only Pd catalysis will be discussed here. 

Complexes ligated by alkylphosphines had been used rarely as catalysts in cross-coupling chemistry, but several studies suggested that they could catalyze the amination of aryl halides with higher selectivity and activity than catalysts of arylphosphines. Steric hindrance promotes reductive elimination at the expense of /3-hydrogen elimination.54 Therefore, reactions of primary amines and, in... 

This section is designed to provide a general overview of activation and coupling chemistry. Some of the reagents discussed in this chapter are not themselves crosslinking or modification compounds, but may be used to form active intermediates with another functional group. These active intermediates subsequently can be coupled to a second molecule that possesses the correct chemical constituents, which allows bond formation to occur. 

Although there are a number of photo-sensitive coupling chemistries that have been used in modification and conjugation reactions (Chapter 2, Section 7), it has been primarily aryl azides... 

Click chemistry reactant pairs used for surface immobilization have the advantage of being stable to aqueous conditions and long-term storage. Unlike many of the other coupling chemistries... 

The use of periodate coupling chemistry for HRP first was introduced by Nakane and Kawaoi (1974 see also Nakane, 1975). In the first step of their protocol, the few amine groups on HRP were initially blocked with 2,4-dinitrofluorobenzene (DNFB) before periodate oxidation. 

Antibody molecules can be labeled with any one of more than a dozen different fluorescent probes currently available from commercial sources. Each probe option has its own characteristic spectral signals of excitation (or absorption) and emission (or fluorescence). Many derivatives of these fluorescent probes possess reactive functionalities convenient for covalently linking to antibodies and other molecules. Each of the main fluorophore families contains at least a few different choices in coupling chemistry to direct the modification reaction to selected functional groups on the molecule to be labeled. These choices include amine-reactive, sulfhydryl-reactive, and carbonyl-reactive. Examples of some of the more popular varieties of fluorescent probes can be found in Chapter 9. 

For additional information on PEG-based reagents and coupling chemistry, see Chapter 18, which discusses the unique discrete PEG compounds. 

Ghosh, S.S., Kao, P.M., McCue, A.W., and Chappelle, H.L. (1990) Use of maleimide-thiol coupling chemistry for efficient syntheses of oligonucleotide-enzyme conjugate hybridization probes. Bioconjugate Chem. 1, 71-76. 

Scheme 6.19 Scaffold decoration of heterocycles using Suzuki cross-coupling chemistry.

Scheme 6.38 Scaffold decoration and modification of heterocycles using Stille cross-coupling chemistry.

Unsymmetrical 3,4-dihalo-l,2,5-thiadiazoles 118 and 119 were prepared from 3-amino-4-chloro-l,2,5-thiadiazole 117 via a Sandmeyer-like reaction involving successively tert-butyl nitrite and either copper bromide or copper iodide in anhydrous acetonitrile (Scheme 17) <2003H(60)29>. The bromo and iodo thiadiazoles 118 and 119 undergo selective Stille and Suzuki C-C coupling chemistry (see Section 5.09.7.6). 

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