Benzyl carbonate Mannich reaction

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

The addition reaction between amines and carbon disulphide has attracted the attention of several research groups because it constitutes a common route to dithiocarbamates. In their latest paper, Fitton and his co-workers, by means of cross-over experiments and the application of optically labelled bases, have further established that the reaction of benzylic, tertiary amines with carbon disulphide proceeds by an inter-molecular addition-elimination-recombination mechanism. On the other hand, Kreutzkamp and his co-workers claim that the insertion reaction of carbon disulphide with tertiary Mannich bases proceeds by an intramolecular mechanism. The synthesis of thiazolidine-2-thiones by the insertion reaction of carbon disulphide with aziridines has been the subject of two recent papers. - One of these deals mainly with the mechanistic and stereochemical aspects of this reaction, which was studied using 2-substituted and cis- and rra/z5 -2,3-disubstituted aziridines as reactants. A mechanism accounting for the stereoselectivity of the reaction has been drawn up by the authors (Scheme 7). 

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