An Alternative Route to 2-Substituted Indoles via N-Aminal-Directed Lithianion.
Alan R. Katrizky, Ping Lue, Ya Xiong Chen, J. Org. Chem. Vol. 55. 3688-3691, 1990
The directing effect of (dialkylamino)methyl (aminal) groups in carbocyclic metalation chemistry is well known. Recently, we have found that aminal groups can also be successfully employed as protecting groups for the NH of heterocyclic compounds and as directing groups for the subsequent lithiation of heterocyclic compounds. This methodology works well for a variety of NH-containing heterocycles, including carbazole, imidazole, benzimidazole, and pyrazole. In all these cases, the aminal group is easily introduced and directs the lithiation to the appropriate site. The removal of the aminal groups is then achieved by gentle warming with aqueous HCl during the workup. Overall, the methodology provides an efficient two-step route to the synthesis of a variety of substituted heterocycles.