Deprotonative metalation of five-membered aromatic heterocycles using mixed lithium-zinc species.
Deprotonation of benzoxazole, benzothiazole, benzo[b]thiophene, benzo[b]furan, N-Boc-protected indole and pyrrole, and N-phenylpyrazole using an in situ mixture of ZnCl(2).TMEDA (0.5 equiv) and lithium 2,2,6,6-tetramethylpiperidide (1.5 equiv) in THF at room temperature is described. The reaction was evidenced by trapping with iodine, regioselectively giving the expected functionalized derivatives in 52-73% yields. A mixture of mono- and disubstituted derivatives was obtained starting from thiazole. Cross-coupling reactions of 2-metalated benzo[b]thiophene and benzo[b]furan with heteroaromatic chlorides proved possible under palladium catalysis. A reaction pathway where the lithium amide and zinc diamide present in solution behave synergically was proposed for the deprotonation reaction, taking account of NMR and DFT studies carried out on the basic mixture.
Synthèse et ElectroSynthèse Organiques, UMR 6510 CNRS, Université de Rennes 1, Bâtiment 10A, Case 1003, Campus Scientifique de Beaulieu, 35042 Rennes, France.
Jean-Martial
JM
L'Helgoual'ch
Anne
A
Seggio
Floris
F
Chevallier
Mitsuhiro
M
Yonehara
Erwann
E
Jeanneau
Masanobu
M
Uchiyama
Florence
F
Mongin
D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D006846:Hydrocarbons, Halogenated / Q000138:chemical synthesis* / Q000737:chemistry; D008094:Lithium / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry*
D006571:Heterocyclic Compounds; D006846:Hydrocarbons, Halogenated; D009942:Organometallic Compounds; D008094:Lithium; D015032:Zinc