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Intramolecular carbolithiation‐cyclization‐electrophilic substitution: solvent effect and mechanistic study
Author(s) -
Rodriguez Cristian,
Nudelman Norma Sbarbati
Publication year - 2014
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.3259
Subject(s) - electrophile , chemistry , intramolecular force , stereocenter , electrophilic substitution , halogen , solvent , computational chemistry , solvent effects , substitution reaction , electrophilic aromatic substitution , combinatorial chemistry , organic chemistry , enantioselective synthesis , alkyl , catalysis
The intramolecular carbolithiation‐cyclization‐electrophilic substitution sequence proves to be a promising strategy for synthetic organic chemists. Our current research in this area focuses on the one‐pot halogen/lithium exchange of 2‐bromophenyl‐3‐phenylprop‐2‐enyl ether, followed by intramolecular carbolithiation, and trapping of the new lithiated cyclic intermediate by several electrophiles, affording 3‐substituted 2,3‐dihydrobenzofurans with some diastereoselectivity. Within this context, a study on the product distribution solvent dependence was carried out using different types of solvents, namely: polar coordinating, polar non‐coordinating, and non‐polar solvents. The results show that the coordinating features of the solvent affect specially the carbolithiation step, whereas the halogen/lithium exchange seems to be barely affected. Theoretical calculations were carried out to investigate the unexpected diastereoselectivity of the tandem reaction , where two stereocenters are generated. Insights gained from our mechanistic investigations enabled us to propose an inversion of configuration at the lithiated intermediate prior to the reaction, being the electrophile the likely cause for the observed distereoselectivity. Copyright © 2013 John Wiley & Sons, Ltd.