Enamines palladium catalysis

In a very useful modification, simple ketones with CH2 adjacent to the carbonyl (cyclic ketones work much better than acyclic ketones) and ortfto-iodo-arylamines react under palladium catalysis to give indoles directly. The use of dimethylformamide as solvent and DABCO as the base are crucial to the success of the route. Mechanistically, the sequence certainly proceeds through the enamine. As well as being conceptually and practically simple, this method tolerates functional groups that would be sensitive to the acid of the traditional Fischer sequence. This method can also be applied to aldehydes, thus providing a direct route to 2-unsubstituted indoles, including side-chain-protected tryptophans. ... 

In a sense, pyrrole can be considered enamine-like in its reactivity, and Dzhemilev and co-workers reported that it acts as a carbon nncleophile, reacting twice with bntadiene nnder palladium catalysis to afford... 

The intramolecular Heck reaction of bromo- or iodoaryl enamines 74 is another versatile key step for the synthesis of indoles. Zero-valent palladium catalysis afforded a mixture of indoles 76 and reduced enamines 74 (X=H) via intermediate formation of 75 depending on the base used [35]. 

All of these processes are of limited synthetic utility because of the requirement of the use of stoi chiometric amounts of palladium complexes. However, by judicious choice of reactants and condition the above-mentioned impediments to catalysis can be overcome. For example, an efficient palladium(II) catalyzed cyclization of o-allyl- and o-vinyl-anilines to indoles has been developed (equation 14).28 Be cause arylamines are -106 less basic than aliphatic amines, and because the cyclized product in thi system gave an enamine (indole) stabilized by aromatization, the problems of catalyst poisoning by sub strate or product were circumvented, and catalysis was successfully achieved. The system was quit tolerant of a variety of functional groups and was used to prepare indoloquinones in excellent yieli... 

A simple method for the direct catalytic allylic alkylation of aldehydes and cyclic ketones has been developed.26 The direct catalytic highly chemo- and regio-selective intermolecular a-allyhc alkylation reaction has been mediated by an unprecedented combination of palladium and enamine catalysis which furnishes a-allylic alkylated aldehydes and cyclic ketones in high yield. 

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