Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Main Authors: Mohamed Yacine Ameur Messaoud, Ghenia Bentabed-Ababsa, Madani Hedidi, Aïcha Derdour, Floris Chevallier, Yury S. Halauko, Oleg A. Ivashkevich, Vadim E. Matulis, Laurent Picot, Valérie Thiéry, Thierry Roisnel, Vincent Dorcet, Florence Mongin
• Format: Article
• Language: English
• Published: Beilstein-Institut 2015-08-01
• Series: Beilstein Journal of Organic Chemistry
• Subjects: CH acidity; indoles; iodolysis; mixed lithium–zinc bases; pyrroles
• Online Access: https://doi.org/10.3762/bjoc.11.160
• ISSN: 1860-5397

The synthesis of N-arylated pyrroles and indoles is documented, as well as their functionalization by deprotonative metallation using the base in situ prepared from LiTMP and ZnCl2·TMEDA (1/3 equiv). With N-phenylpyrrole and -indole, the reactions were carried out in hexane containing TMEDA which regioselectively afforded the 2-iodo derivatives after subsequent iodolysis. With pyrroles and indoles bearing N-substituents such as 2-thienyl, 3-pyridyl, 4-methoxyphenyl and 4-bromophenyl, the reactions all took place on the substituent, at the position either adjacent to the heteroatom (S, N) or ortho to the heteroatom-containing substituent (OMe, Br). The CH acidities of the substrates were determined in THF solution using the DFT B3LYP method in order to rationalize the experimental results.