Tetrazoles directed lithiation

No heterocycle containing a C=N bond is as powerful a director as the oxazolines or tetrazoles described above, but their imidazoline analogues 132 direct well if deprotonated to the amidine equivalent 133 of a secondary amide anion (Scheme 61). Pyrazoles 134 also direct lithiation, but need protecting with a bulky Af-substituent to prevent nucleophilic attack by the base (Scheme 62). ... 

Substituted 1,2,3-triazoles, 1,2,4-triazoles and tetrazoles are metallated by n-butyllithium at low temperature at the 5-position. At room temperature 5-lithium derivatives tend to undergo ring opening. No direct lithiation of a 2-substituted 1,2,3-triazole has been reported. 

The ort/io-directing properties of the (aryloxy)tetrazole functionality has been demonstrated for the first time and rapid anionic rearrangement of the resulting lithiated derivative to form 5-(hydroxyaryl)-l-phenyl-l//-tetrazoles has been reported. ... 

Recently the tetrazole moiety has attracted interest as a useful directing group for the lithiation of 5-aryl substituents, with the dianion derivative 62 being obtained in the case of the unsubstituted parent compound and the monolithio species 63 in the case of the 2-trityl derivative (91TL6857 91USP50398I4). With both systems, good yields of products were obtained after reaction with a variety of electrophiles. 

A variety of heterocyclic systems containing unsaturated nitrogen can partake in directed aromatic or heteroaromatic lithiations. Pyrazole (II,D), tetrazole (II,G,2), imidazoline (V,B,2), and pyridine (IV,A,4) derivatives were discussed in the sections indicated. In addition, lithio derivatives of 2-oxazoline 178 (76LA183), 4,4-dimethyl-2-oxazoline 179 (790R1 85T837),... 

A tetrazole can also act as an ortho-dvrocXmg group, as in the lithiation of 5-phenyltetrazole. A tetrazol-5-yl ether similarly directs ort/jo-metaUation, but here the tetrazole migrates from the oxygen to the lithiated carbon. ... 

Tetrazole can be lithiated on the 5-position however, attempts to carry out substitution reactions sometimes fail because the intermediates are easily cleaved and eliminate nitrogen above -50 A series of 1,5-disubstituted tetrazoles were synthesized from a Pd/Cu catalyzed direct arylation of 1-substituted tetrazoles in the presence of tris(2-furyl)phosphine (TFP) and cesium carbonate. ... 

The role of organolithium aggregates and mixed aggregates in organolithium mechanisms has been reviewed. The synthetic utility of the regio- and stereo-selective lithiation of aziridines has been highlighted. " The latest developments on the direct metallation (mainly lithiation chemistry) of various 1,2,3-triazoles, 1,2,4-triazoles, tetrazoles, and 1,3,4-oxadiazoles have been presented. ... 

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