Deprotonative Magnesation and Cadmation of [1,2,3]Triazolo[1,5-a]pyridines

Abstract

[1,2,3]Triazolo[1,5-a]pyridine and 3-substituted derivatives were regioselectively metalated at the 7 position using either Bu3MgLi or (TMP)3CdLi, the former at −10 °C and the latter at room temperature. The lithium arylmagnesates (R = H, Me, Ph) proved to react with iodine (34−75%) or 3,4,5-trimethoxybenzaldehyde (32−51%). Attempts to obtain the cross-coupling products using 2-bromopyridine under palladium catalysis failed, a result attributed to the low stability of these compounds. The corresponding lithium arylzincates reacted in 17−60% yield under the same reaction conditions. The lithium arylcadmates were either trapped with iodine (38−76%, R = H, Me, Ph, CN, 2-thienyl) or involved in palladium-catalyzed cross-coupling reactions with 2-bromopyridine (26−67%, R = H, Me, Ph). For R = 2-pyridyl, 3-(6-iodo-2-pyridyl)-[1,2,3]triazolo[1,5-a]pyridine was isolated in 73% yield. (TMP)3CdLi also proved suitable for the clean dideprotonation of two substrates (R = H, 2-thienyl), a result demonstrated by quenching with iodine (66−75%).

Regio‐ and Chemoselective Metalation of Arenes and Heteroarenes Using Hindered Metal Amide Bases

“…[93,128] Thus, by using cadmium base 102, a substituted triazolopyridines such as 103 produces the cadmium reagent 104 (25 8C, 2 h). [129] Subsequent iodolysis furnished the iodotriazolopyridine 105 in 65 % yield (Scheme 22). [93,128,130] Ethyl isonicotinate is regioselectively cadmated using TMP 3 CdLi (102; 25 8C, 2 h) to furnish, after iodolysis, the substituted nicotinate 106 in 65 % yield.…”

“…[128,131] Furthermore, the use of TMEDA-solvated TMP 3 CdLi (102) improves and simplifies the reaction protocol, since CdCl 2 ·TMEDA is less hygroscopic than CdCl 2 . [129,131] Remarkably, a range of substituted ferrocenes are converted into organocadmium species by TMP 3 CdLi (102). Thus, the ferrocene 107 leads, after cadmation with 102 (1 equiv, 25 8C, 2 h) and subsequent iodolysis, to the diiodoferrocene 108 in 82 % yield (Scheme 22).…”

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).…”

Microwave‐Assisted 1,3‐Dipolar Cycloaddition: an Eco‐Friendly Approach to Five‐Membered Heterocycles

“…synthesis of 202, Scheme 72). [131] A similar synthetic strategy was applied to the synthesis of 1,3-dioxol- anes with aldehydes acting as dipolarophiles. [132] The mechanisms of 1,3-dipolar cycloadditions between carbonyl ylides and aldehydes or imines have been theoretically investigated by DFT methods.…”

“…[132] The mechanisms of 1,3-dipolar cycloadditions between carbonyl ylides and aldehydes or imines have been theoretically investigated by DFT methods. [131] Scheme 72.…”