Titanium-Catalyzed Intermolecular Hydroamination Route to Pyrroles

Significance

Based on previous results (L. Ackermann Synlett 2007, 507) two methodologies have been developed for the regioselective preparation of fully substituted pyrroles via titanium-catalyzed intermolecular hydroamination of a dia­stereoisomeric mixture of chloroenynes 2. This is the first report of such a pyrrole synthesis using a mixture of chloroenynes (E/Z)-2 for which an expected mechanism has been proposed. However, since derivatives 2 are often tedious to prepare, the use of the easily prepared α-haloalkynols 1 is an advantage of this method. The final pentasubstituted pyrroles are obtained via electrophilic aromatic substitution reactions within a one-pot protocol.