Newer Coupling Reagents

There are dozens of new reagents that have been developed and examined for their coupling efficiency. Most are composed of a good leaving group derived from a 

FIGURE 7.29 Abbreviated structures of some new coupling reagents with complete names omitted. Diethylphosphoryl-,106 108 ODhbt, HAPyU,107 dimethylaminium-,109 ditolylphosphinyl-, and 5-aza-Dhbt-.110 

A Chang, YK Ko. Benzotriazol-l-yl diethyl phosphate. A new convenient coupling reagent for the synthesis of amides and peptides. Tetrahedron Lett 26, 1341, 1985. 

A Ehrlich, M Brudel, M Beyermann, R Winter, LA Carpino, M Bienert. Cyclization of all L pentapeptides by means of HAPyU. Peptides 1994. Proceedings of the 23rd Peptide Symposium, Escom, Leiden, 1995, pp 167-168 

J-C Xu. New and highly efficient immonium type peptide coupling reagents synthesis, mechanism and application. Tetrahedron 56, 4437, 2000. 

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Several newer methods take advantage of the highly selective nature of organopaHadium reagents. A palladium acetate-triarylphosphine catalytic system has been employed to induce the coupling of bromobenzene with the desired acrylate ester (13). 

The nitrosochlorination of alkenes has been reviewed.146 The products of nitrosochlorination are often dimers due to the propensity of nitroso groups to couple with one another. For this reason, and because of the advent of newer reagents, modem synthetic uses of NOC1 are scarce. Instances where NOC1 has proven to be a useful reagent include the preparation of a-oximinocarbonyl compounds (Scheme 71)147 and the synthesis of precursors of insect growth regulators (Scheme 72).148... 

The process of separation and quantitation of amino acids has been automated. In one automated method, a single cation exchange resin column separates all the amino acids in the protein hydrolysate. The analyzer is capable of detecting as little as 1-2 nmol of an amino acid and a complete analysis can be obtained in about 4 hours. In newer procedures, the complete analysis can be performed in about Ihour and permit detection of as little as 1-2 nmol of an amino acid. Picomole amounts of amino acids can be determined when the separated amino acids are coupled to fluorescent reagents such as o-phthalaldehyde. Amino acid separation and quantitation can also be accomplished by reverse-phase high-pressure liquid chromatography of amino acid derivatives—a rapid and sensitive procedure. 

Several types of organosilicon compounds can be used in cross coupling, fluoride usually being required to activate the silicon for the transmetallation in the earlier examples. Silanols are newer and more versatile reagents, in particular dimethylsilanols, which are used with bases - either reversible (aUcoxides and cesium carbonate) or irreversible (sodium hydride aud sodium hexamethyldisilazide). lu the latter case, the silauo-ate salts can be isolated and stored. ... 

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