The diastereocontrolled preparation of a series of 10-aryl-substituted pyrroloisoquinolines is achieved through a synthetic design that involves two key cyclization steps. First, the iodine(III)-mediated reaction of a series of N-benzylpentynamides leads to the generation of the 5-aroylpyrrolidinone skeletons. Finally, after reduction of the generated ketone group into the corresponding carbinol, the effect of a number of different acidic conditions was studied to assist the second cyclization step that occurs through an aromatic electrophilic substitution process. The study of the stereochemical course of this step led us to conclude that it takes place through a S(N)1 mechanism with very high (>95% anti) diastereocontrol.
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