Pyrazoles, 4-lithio- derivatives

In different seetions of this ehapter, pyrazoles and indazoles C-linked to a metal or a metalloid have been deseribed or they will be deseribed in the preparative seetions, ineluding lithio derivatives (Seetion 4.04.2.1.7), pyrazolylmagnesium reagents (Seetion 4.04.2.3.7(iii)), ehloromereury derivatives (Seetion 4.04.2.1.4(vii)) and silylpyrazoles (Section 4.04.3.1.2(ii)). All these compounds are useful intermediates and some of their most characteristic reactions will be dijcussed here. 

Less success has been obtained with removable N-substituents, however, the trityl and THP derivatives of 4-bromopyrazole both giving low yields of products derived from reaction of the lithio derivatives with carbonyl compounds [62CB222 82ACS(B)101]. Magnesium metal has also been used to produce l-methyl-4-(trimethylsilyl)pyrazole by an in situ Grignard reaction on the analogous 4-bromo compound in HMPT (84JOC4687). 

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),... 

Thiophenes furans and pyridines are in general the most readily available of the various hetero-aromatic systems and therefore we have carried out a great deal of metallation and derivatization reactions with these compounds. Furan and thiophene are cheap starting compounds and the stability of their easily obtainable 2-lithio derivatives permits reactions with a variety of electrophilic reagents. Hetero-aromatics with two or more hetero atoms (e.g. thiazoles, pyrazoles, oxazoles) are less readily available, and some of their metal derivatives have a low thermostability (cyclofragmentations). For these reasons their metallation and functionalization reactions have been studied less extensively [1]. 

Aromatic SAMP-hydrazones [45 SAMP = (S)-aminomethoxymethylpyrrolidine] react with the lithio derivative of methoxyaUene to yield enantiopure 3-pyrrolines. Homochiral nitrile imines (46) can be generated in situ by base treatment of hydrazonyl chlorides (47) (46) undergoes diastereoselective formation of furo[3,4-c]pyrazole derivatives [(48), easily separable isomers], via intramolecular cycloaddition. 

Die Einfiihrung der Sulfo-Gruppe bzw. seiner Derivate in die 5-Position gelingt iiber die 5-Lithio-lH-pyrazole mit Schwefeldioxid als Elektrophil1667 2476. 

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