Combinatorial chemistry Stille couplings

In addition, further automation will be needed in what is still very much a hands-on art. Autoinjectors coupled to complete analytical data systems and readers for 96-well plates are the beginning of what will continue to be a necessary trend of residue chemistry. The application of the techniques of combinatorial chemistry/biochemistry, which has produced screening methodology for handling many variables, might be appropriate to residue chemistry. 

A Stille coupling of a bromopyridine on solid support was described by Snieckus group [101]. Merrifield resin 119 was esterified with 3-bromopyridine-5-carboxylic acid to afford ester 120. The Stille coupling of ester 120 on a solid support led to the expected hetero phenylpyridine 121, which was then cleaved via basic hydrolysis to produce 122. Snieckus work has the potential for application to combinatorial chemistry and high throughput screening. 

Of particular interest to combinatorial chemistry is the use of immobilised functionalised boronic acid templates which are capable of further transformations [20]. For instance, an aryl carboxylic acid 50 can be converted into the corresponding amide 51 (Scheme 12), whilst still being attached to the resin. Benzyl amine and butylamine were coupled efficiently to afford (after cleavage) the corresponding amides 52 in high yield (Scheme 12). 

As far as catalysis is concerned it is already benefiting from new developments such as supercritical fluids, ionic liquids, sol-gel technology, solid phase reactions, parallel and combinatorial chemistry and some of these can be coupled to microwave irradiation. Already a number of very efficient organometallic (mainly iridimn based) catalysts have been produced although we are still some way from the acid, base situation where tritia-tion (or detritiation) rates can be estimated from a knowledge of acid-base strengths. 

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