Organolithiums in Synthesis

Reactions of organolithium reagents with quinazoline derivatives

“…The rate and regioselectivity of ortho-lithiation seems to be controlled not only by coordination between the lithium reagent and the heteroatom of the DMG but also by the acidity of the proton at the ortho-position. 12 It is not clear which factor is the principal driving force in ortho-lithiation. However, both of them could play a role for lithiation to be successful.…”

“…[12][13][14][15][16] The rapid expansion of the list of functionalities capable of directing lithiation has made this approach an important strategy for the synthesis of various regiospecifically substituted benzenes and heterocycles. [57][58][59][60][61][62][63][64] The addition of organolithium reagents to the imine bond of pyridine and related nitrogen heterocycles is a well-established reaction.…”

“…12 It is believed that alkyl bromides react with alkyllithiums via the radical mechanism, while aryl bromides react via ate complexes as intermediates. 12,56 Scheme 34. Bromine-lithium exchange of alkyl bromide via radical intermediate.…”

“…1,2 A number of alternative approaches have therefore been developed for regioselective ortho-disubstitution, and lithiation followed by electrophilic substitution is one of the most recognized and efficient. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] Directed lithiation of aromatic compounds 1 comprises deprotonation of a site ortho to a substituent that possesses a heteroatom (e.g. oxygen, nitrogen or sulfur) by use of a base.…”

Mesityllithium

“…[1][2][3] Amongst the other reagents, mesityllithium has occupied an important place because of its non-nucleophilicity, strongly basic nature, clean selective reactivity and easy preparative methods. 2-Bromomesitylene is treated with tert-butyllithium in THF solution, a method that leads to a 1:1 mixture of the reagent and lithium bromide (Scheme 1).…”