Deprotonative cadmation of functionalized aromatics

Abstract

This communication describes the deproto-metalation of a large range of aromatics including heterocycles using a newly developed lithium-cadmium base; the reaction proceeds at room temperature with an excellent chemoselectivity and efficiency, and proved to be regioselective in most cases.

Carboxylation of indoles and pyrroles with CO2 in the presence of dialkylaluminum halides

“…9 It has been a hot and fascinating topic that the alkali metal-mediated magnesiation, 20 zincation, 20,21 alumination, 22 cupration, 23 and cadmation 24 of aromatic compounds, including indoles and pyrroles, have been achieved by using ate bases [20][21][22][23][24] or a neutral base. 21b It should be noted that Me 2 AlCl metalated 1-methylindole (1a) at the 3-position (vide supra), while an ate base, i-Bu 3 Al(TM-P)Li, metalates 1-(Boc)indole at the 2-position.…”

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

“…[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).…”

“…[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). [130] Detaillierte NMR-spektroskopische Untersuchungen und DFT-Rechnungen bestätigen die Struktur von 102 als eigentliches Metallierungsreagens.…”

“…[130] Detaillierte NMR-spektroskopische Untersuchungen und DFT-Rechnungen bestätigen die Struktur von 102 als eigentliches Metallierungsreagens. [128,131] Des Weiteren vereinfacht die Verwendung von TMEDA-solvatisiertem TMP 3 CdLi (102) …”

Structurally Defined Potassium‐Mediated Zincation of Pyridine and 4‐R‐Substituted Pyridines (R=Et, iPr, tBu, Ph, and Me2N) by Using Dialkyl–TMP–Zincate Bases

“…Often superior in terms of functional-group tolerance, compatibility with more organic substrates, and milder experimental conditions than classical lithiation methods, these new metalations, which are zinc–hydrogen exchange reactions assisted by the presence of a charge-balancing alkali metal cation, can be interpreted as “alkali-metal-mediated zincations” (AMMZn) [2]. A range of other mildly electropositive, soft metals including aluminum,[3] cadmium,[4] iron,[5] magnesium,[6,1] and manganese[7] have similarly been transformed into powerful selective metalating agents through this special alkali-metal-mediated phenomenon. Two widely studied reagents in the context of AMMZn are TMP based, one being the lithium–zincate [Li(tmp)Zn( t Bu) 2 ] (TMP=2,2,6,6-tetramethylpiperidide) developed by Kondo and Uchiyama[8, 2c ] and the other is the sodium analogue [(tmeda)Na(μ- t Bu)(μ-tmp)Zn( t Bu)] (TMEDA= N , N , N′ , N′ -tetramethylethylenediamine) made by our own group, [2b] whereas Knochel has recently introduced an efficient zincating reagent by mixing the lithium–magnesiate Mg(tmp) 2 ⋅ 2LiCl with the halide ZnCl 2 [9]…”