Intramolecular carbolithiation‐cyclization‐electrophilic substitution: solvent effect and mechanistic study†. (10th December 2013)

• Record Type: Journal Article
• Authors: Rodriguez, Cristian; Nudelman, Norma Sbarbati; Nome, Faruk
• Is Part Of: Journal of physical organic chemistry. Volume 27:Number 4(2014:Apr.)
• Page Start: 322
• Page End: 326
• Publication Date: 2013-12-10
• Subjects: Chemistry, Physical organic -- Periodicals; 547.1
• DOI: 10.1002/poc.3259
• Languages: English
• ISSNs: 0894-3230

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">intramolecular</named-content> 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 <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">intramolecular</named-content> carbolithiation, and trapping of the new lithiated cyclic <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">intermediate</named-content> 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.</p> <p>Theoretical calculations were carried out to investigate the unexpected diastereoselectivity of the <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">tandem reaction</named-content>, where two stereocenters are generated. Insights gained from our mechanistic investigations enabled us to propose an <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">inversion</named-content> of configuration at the lithiated <named-content content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">intermediate</named-content><italic>prior</italic> to the reaction, being the electrophile the likely cause for the observed distereoselectivity. Copyright © 2013 John Wiley & Sons, Ltd.</p> </abstract>