Amide arylation

More recent developments in the field of the Pirkle-type CSPs are the mixed r-donor/ r-acceptor phases such as the Whelk-Of and the Whelk-02 phases.The Whelk-Of is useful for the separation of underiva-tized enantiomers from a number of families, including amides, epoxides, esters, ureas, carbamates, ethers, aziridines, phosphonates, aldehydes, ketones, carboxylic acids, alcohols and non-steroidal anti-inflammatory drugs.It has been used for the separation of warfarin, aryl-amides,aryl-epoxides and aryl-sulphoxides. The phase has broader applicability than the original Pirkle phases. The broad versatility observed on this phase compares with the polysaccharide-derived CSPs... 

The intermolecular Pd-catalyzed amination of haloindoles [475] and indoleboronic acids [476] and the A -arylation [477] and TV-vinylation of indoles [478] have been described. A method for a tandem carbon-hydrogen functionalization/amide arylation leads to carbazoles, e.g. 410 [479]. 

In addition to aryl oxycarboxylic acids, aryl oxycarboxylic acid amides, aryl oxycarboxylic acid nitriles and, after oxidation, aryl oxyalkanoles can undergo /9-oxidation. 

Many physicochemical properties can be used as a filter to discard unwanted molecules. However, strict filters can be unsatisfactory. For example, a molecule of molecular weight 399 may be accepted, whilst that of 401 rejected. If the latter molecule contained a novel 3D core, and the former was yet another benzodiazepine or aryl-amide-aryl-amine type, one might question the decision. Therefore, researchers adopted more subtle penalty functions. which increase the further away a molecule is from the ideal. Figure 14.4 illustrates the most common penalty functions. 

Other organometaloids also undergo similar reactions. Analogous Cu(OAc)2 mediated reaction of aryltins, arylsiloxanes, arylbismuth compounds, and arylleads with various amines lead to arylated products in good yields. An interesting modification of amine or amide arylation by aryl boronic acids mediated... 

Synthesis of Nitriles from Amides. Aryl carboxamides and other electron-rich amides could be converted to the corresponding nitriles in good yields by treatment with Ag20 and EtI in benzene at reflux (eq 23). This technique is typically compatible with acid-labile moieties or protecting groups (TBDPS, isopropy-lidene). Although this technique was found to be very efficient for the transformation of electron-rich carboxamides, simple aliphatic amides are rarely suitable for this purpose. 

By definition, palladium- and copper-catalyzed aryl amidation, aryl etherification, and aryl thioetherification reactions are transformations designed to construct bonds between heteroatoms and aromatic rings. Thus, it is perhaps not surprising that these... 

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