Deprotonative Metalation of Functionalized Aromatics Using Mixed Lithium–Cadmium, Lithium–Indium, and Lithium–Zinc Species

Abstract

In situ mixtures of CdCl(2)TMEDA (0.5 equiv; TMEDA = N,N,N',N'-tetramethylethylenediamine) or InCl(3) (0.33 equiv) with [Li(tmp)] (tmp = 2,2,6,6-tetramethylpiperidino; 1.5 or 1.3 equiv, respectively) were compared with the previously described mixture of ZnCl(2)TMEDA (0.5 equiv) and [Li(tmp)] (1.5 equiv) for their ability to deprotonate anisole, benzothiazole, and pyrimidine. [(tmp)(3)CdLi] proved to be the best base when used in tetrahydrofuran at room temperature, as demonstrated by subsequent trapping with iodine. The Cd-Li base then proved suitable for the metalation of a large range of aromatics including benzenes bearing reactive functional groups (CONEt(2), CO(2)Me, CN, COPh) or heavy halogens (Br, I), and heterocycles (from the furan, thiophene, pyrrole, oxazole, thiazole, pyridine, and diazine series). Five-membered heterocycles benefiting from doubly activated positions were similarly dideprotonated at room temperature. The aromatic lithium cadmates thus obtained were involved in palladium-catalyzed cross-coupling reactions or simply quenched with acid chlorides.

Transforming LiTMP Lithiation of Challenging Diazines through Gallium Alkyl Trans‐Metal‐Trapping

“…In the crystal, 5 follows the pattern in the TMT diazine series with the GaR 3 and Li(PMDETA) units adjacent on deprotonated C and N atoms, respectively, with a Ga1‐C13‐N1‐Li1 torsion angle of −13.9(4)° (Figure 4). This first Ga TMT reaction of a N‐S heterocycle is competitive with Mongin's LiTMP/CdCl 2 ⋅TMEDA in THF solution approach, which used excess (1.5) base equivalents for a 97 % yield of 2‐iodobenzothiazole after I 2 quenching, though no metallo intermediate was identified 7b, 15…”

Review. Regioselective Functionalization of Pyridines using a Directed Metalation or a Halogen/Metal Exchange

“…The use of the related lithium cadmiate base TMP 3 CdLi allows a smooth metalation of 3-cyanopyridine (24). After iodolysis, the iodopyridine 25 is obtained in 61 % yield (Scheme 7) [34,35].…”

Regio‐ und chemoselektive Metallierung von Arenen und Heteroarenen mit gehinderten Metallamidbasen

“…Infolgedessen konzentrierten sich jüngste Untersuchungen auf Dimetall-TMP-Basen, wie Magnesiate, [84][85][86][87][88] Zinkate, [89,90] Aluminate, [91,92] Cadmate, [93] Chromate, [94] Manganate [95] und Ferrate. [94] Das TMP-Anion in diesen Reagentien ist ausnahmslos der einzige oder zumindest der aktivste Basenligand, der die Metallierung des Substrats ermçglicht.…”

“…[127] Mongin und Uchiyama beschrieben die neue Base TMP 3 CdLi (102), die sie aus CdCl 2 ·TMEDA und TMPLi (1) erhielten. [93] Substituierte Arene und Heteroarene mit empfindlichen Funktionen, beispielsweise Ester-, Cyan-und Ketogruppen, werden regioselektiv metalliert. [93,128] Die Cadmiumbase 102 wandelte substituierte Triazolpyridine wie 103 in das entsprechende Cadmiumreagens 104 um (25 8C, 2 h), [129] dessen Iodolyse anschließend das Iodtriazolpyridin 105 in 65 % Ausbeute lieferte (Schema 22).…”

“…[93] Substituierte Arene und Heteroarene mit empfindlichen Funktionen, beispielsweise Ester-, Cyan-und Ketogruppen, werden regioselektiv metalliert. [93,128] Die Cadmiumbase 102 wandelte substituierte Triazolpyridine wie 103 in das entsprechende Cadmiumreagens 104 um (25 8C, 2 h), [129] dessen Iodolyse anschließend das Iodtriazolpyridin 105 in 65 % Ausbeute lieferte (Schema 22). [93,128,130] Isonicotinsäureethylester wird von 102 (25 8C, 2 h) regioselektiv cadmiert und durch anschließende Iodolyse in die substituierte Isonicotinsäure 106 überführt (65 % Ausbeute).…”