Unravelling Factors Affecting Directed Lithiation of Acylamino­aromatics

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 Introduction2 Lithiation with DMG Attached Directly to the Phenyl Ring2.1 Influence of the DMG2.2 Influence of Substitution on the Phenyl Ring3 Lithiation with the DMG Separated by a CH2 Group from the Phenyl­ Ring3.1 Effect of the DMG3.2 Influence of Substitution on the Phenyl Ring4 Lithiation with the Phenyl Ring and DMG Separated by Two or More CH2 Groups4.1 Effect of the DMG and Its Distance from the Phenyl Group4.2 Effect of Substituents on the Phenyl Ring5 Conclusions

Facile, mild and efficient synthesis of azines using phosphonic dihydrazide

“…[24] In the current work, a novel series of azines was produced by simple and efficient synthetic procedures from phosphonic dihydrazide, as part of our research program on the synthesis of novel heterocycles. [25][26][27][28][29] KEYWORDS Phosphonic dihydrazide; azines; nucleophilic substitution reaction; heterocycles; bis(N'arylpropanehydrazonoyl produced in low yields along with 1. Such results are not in agreement with the reported ones.…”

Studies on a catalytic version of the Matteson asymmetric homologation reaction

“…25 However, the process needed a significant (five-fold) excess of the chiral ligand in order to provide a good level of asymmetric induction in the reaction studied, ostensibly because lithium chloride generated in situ competed for the ligand. 25 As part of our interest in the use of organometallic intermediates and in particular boron reagents in organic syntheses, [26][27][28][29][30][31][32] we decided to investigate this procedure in more detail in the hope that we may be able to overcome the difficulties and develop a procedure that was successful with a much smaller quantity of chiral ligand. We now report our results.…”

Reactions between lithiated 1,3-dithiane oxides and trialkylboranes

“…We have been extensively involved in the development of useful synthetic methods that utilize boron and lithium intermediates [22][23][24][25][26][27][28][29][30][31]. We therefore turned our attention towards reactions between trialkylboranes and appropriate lithiated 1,3-dithiane oxides derived from 1, including trans-1,3-dithiane-1,3-dioxide 2, a mixture of cisand trans-2-chloro-1,3-dithiane-1,3-dioxides 3, and 2-substituted 1,3-dithiane-1-oxides 4-6 (Figure 1).…”