Other Supported Coupling Reagents

Triazines, such as 2,4,6-trichloro[l,3,5]triazine and 2-chloro-4,6-dimethoxy [l,3,5]triazine are known selective coupling reagents for amide synthesis [73]. 

59 with NMM generated the supported morpholinium salt 60, which reacted with aliphatic and aromatic carboxylic acids to give the resin loaded with the carboxylate 61, which can even be dried and stored. Reaction of anchored activated ester 61 with amines in the presence of NMM gave the corresponding amides in good yields (60-87%). 

Poly (ethylene glycol) (PEG) 4000 has been employed for the preparation of a PEG-anchored version of the previous dichlorotriazine reagents after its reaction with 2,4,6-trichloro[l,3,5]triazine in the presence of NMM [75]. This polymeric reagent (64) has been used for the preparation of anchored benzoic acid derivatives in the presence of NMM and THF as solvent, the supported activated esters being precipitated by addition of ether. Their further reaction with aliphatic and aromatic amines as bases afforded the corresponding amides in good yields, although sec- 

6-Trichloro[l,3,5]triazine has also been attached to the Wang resin. Reaction of the resulting supported dichlorinated triazine with 2-(2-aminoethoxy)ethanol and further treatment again with an excess of 2,4,6-trichIoro[l,3,5]triazine afforded resin 65, which has been shown to be effective in the conversion of carboxylic acids into acid chlorides, using triethylamine as base in dichloromethane or acetone as solvent [78]. The obtained acid chlorides can be easily transformed into ester or amides after removal of the resin by filtration and addition of an alcohol or an amine. From the isolated yields of the esters or amides it could be deduced that the yields of the obtained acid chlorides are around 70-90%. However, a chiral amino acid was completely racemized under this resin treatment. 

A special case of acylation of amines occurs when using the chiral supported 1,2-disulfonamide 66 (0.58mmolg 1 loading), which can be considered the first polymeric reagent employed in the kinetic resolution of primary amines through enantioselective acetylation of one of the enantiomers in the racemic mixture [79]. The Merrifield-derived chiral scaffold could be quantitatively recovered and recycled. 

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More recently, automated gene synthesizers have been developed that operate on principles similar to the Merrifield solid-phase technique for peptides. A protected nucleotide is covalently bonded to a polymer. Other protected nucleotides are then added sequentially to the chain, using a coupling reagent. Eventually, the protecting groups are removed, and the synthetic oligonucleotide is then detached from the solid support. 

Iron-catalyzed cross-coupling reactions of various acyl chlorides or thioesters with Grignard reagents have been pioneered by Marchese et al. and other research groups.322 These transformations provide general and convenient access to a wide range of ketones and have been further extended to the use of a supported iron(lll) complex.323... 

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