Issue in Honor of Prof. Dr. Manfred Schlosser ARKIVOC 2015 (iv) 19-47 Page 19 © ARKAT-USA, Inc. Directed lithiation of simple aromatics and heterocycles for synthesis of substituted derivatives Gamal A. El-Hiti,* a Keith Smith,* b Amany S. Hegazy, b Mohammed B. Alshammari, c and Ali M. Masmali a a Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia b School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK c Chemistry Department, College of Sciences and Humanities, Salman bin Abdulaziz University, P.O. Box 83, Al-Kharij 11942, Saudi Arabia E-mail: gelhiti@ksu.edu.sa, smithk13@cardiff.ac.uk Dedicated to Professor Manfred Schlosser to mark the scientific achievements within his career DOI: http://dx.doi.org/10.3998/ark.5550190.p008.744 Abstract Directed lithiation of substituted aromatics and heterocycles containing a directing metalating group with alkyllithium in anhydrous tetrahydrofuran or diethyl ether at low temperature provides the corresponding lithium intermediates. Reaction of the lithium reagents obtained in situ with various electrophiles gives the corresponding substituted derivatives in high yields. The process has been applied for various derivatives and has proven to be a convenient method for modification of ring systems. This brief review highlights the importance of directing metalating groups in directed lithiation of simple aromatic compounds and some common heterocycles as a tool for regioselective substitution. Keywords: Lithium reagents, directed lithiation, lithium intermediates, electrophiles, substituted aromatics, heterocycles, synthesis Table of Contents 1. Introduction 2. Directed lithiation of benzenoid compounds 3. Directed lithiation of naphthalenes