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Synthesis 2018; 50(18): 3634-3652
DOI: 10.1055/s-0036-1591954
short review
© Georg Thieme Verlag Stuttgart · New York

Unravelling Factors Affecting Directed Lithiation of Acylamino­aromatics

Keith Smith*
a   School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK   Email: smithk13@cardiff.ac.uk
,
Mohammed B. Alshammari
b   Chemistry Department, College of Sciences and Humanities, Prince Sattam bin Abdulaziz University, P.O. Box 83, Al-Kharij 11942, Saudi Arabia
,
Gamal A. El-Hiti*
c   Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia   Email: gelhiti@ksu.edu.sa
› Author Affiliations
Further Information

Publication History

Received: 13 February 2018

Accepted: 15 February 2018

Publication Date:
27 March 2018 (online)

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Published as part of the Special Section on the Main Group Metal Chemistry Symposium

Abstract

Ureas, pivalamides, and carbamates are widely used as directing metalation groups (DMGs) due to their good directing ability, low cost, ease of access, and ease of removal. Lithiation of substituted benzenes having such directing metalation groups using various alkyllithiums in anhydrous solvent at low temperature provides the corresponding lithium intermediates, but lithiation may take place at various sites. Reactions of the lithium reagents obtained in situ with various electrophiles give the corresponding derivatives, typically substituted at the site(s) where initial lithiation occurred, often in high yields. However, it is often difficult to predict what reagents and/or conditions might be needed to give specific products or to draw general conclusions about the factors that influence the reactions, especially when the reagents, temperature, and solvents used in reported reactions are not directly comparable. In this review, therefore, we attempt to unravel the various factors that influence the lithiation of various simple aromatic compounds containing urea, pivalamide, and carbamate groups.

1 Introduction

2 Lithiation with DMG Attached Directly to the Phenyl Ring

2.1 Influence of the DMG

2.2 Influence of Substitution on the Phenyl Ring

3 Lithiation with the DMG Separated by a CH2 Group from the Phenyl­ Ring

3.1 Effect of the DMG

3.2 Influence of Substitution on the Phenyl Ring

4 Lithiation with the Phenyl Ring and DMG Separated by Two or More CH2 Groups

4.1 Effect of the DMG and Its Distance from the Phenyl Group

4.2 Effect of Substituents on the Phenyl Ring

5 Conclusions

Keywords

lithium reagents - directed lithiation - ureas - pivalamides - carbamates - electrophiles - lateral lithiation