Synthesis of isomeric pyrroloquinolines from 5- and 6-aminoindoles

Abstract

In the case of 2,3-dimethyl-, 2-methyl-, and 2,3,6-trimethyl-5-aminoindoles, as well as 2,3-dimethyl- and 1,2,3-trimethyl-6-aminoindoles, it was shown that the enamino ketones formed in the reaction of 5- or 6-aminoindoles with 1,3-diketones undergo cyclization under the influence of acidic agents to substituted pyrroloquinolines with linear or angular ring fusion. The formation of the latter is limited by steric factors. Thus, the pronounced ortho effect of a substituent attached to the C atom (in the pyrrole ring) or 5-indolylaminovinyl ketones substantially hinders cyclization in the 4 position of the indole and promotes primary or exclusive formation of the linear isomer. Similarly, in the case of enamino ketones obtained from 6-aminoindoles, the substituent attached to the pyrrole nitrogen atom sterically hinders electrophilic attack at C₇, i.e., formation of the angular isomer.