Effiziente Synthese funktionalisierter zinkorganischer Verbindungen durch direkte Insertion von Zink in organische Bromide und Iodide

Abstract

Eine Menge Verbindungen: Ein breites Spektrum an funktionalisierten (hetero)aromatischen und aliphatischen Zinkreagentien kann problemlos in Tetrahydrofuran hergestellt werden. Zur Anwendung kommt dabei eine durch Lithiumchlorid vermittelte Zinkinsertion (siehe Schema; All=Allyl).

Fischer Indole Synthesis with Organozinc Reagents

“…Thus, the reaction of ethyl 4-bromobutanoate (7 a, 1.1 equiv) with zinc dust (2 equiv), ZnBr 2 (2 equiv), [12] and LiCl (1.1 equiv) in THF produces the expected alkylzinc halide 6 a in 90 % yield (50 8C, 1 h). [13] The addition of a solution of 6 a (1 equiv) in THF to the functionalized aryldiazonium tetrafluoroborate 5 a (1.25 equiv, À60 8C to 258C) is thought to produce an azo compound of type 4 B, which isomerizes to the unsaturated hydrazine 4 A. Me 3 SiCl (1 equiv) is added and the reaction mixture is heated using microwave irradiation (125 8C, 90 min) to furnish after standard workup the polyfunctional indole 1 a in 90 % yield.…”

“…The benzylic zinc reagent 6 d [16] reacted with 4-methoxybenzenediazonium tetrafluoroborate (5 e) providing, after microwave irradiation (125 8C, 90 min), the expected 2-phenylindole derivative 1 m in 46 % yield (Table 1, entry 11). Secondary cycloalkylzinc halides such as 6 e-g [13,12] add to functionalized aryldiazonium salts (5 a-g) furnishing after microwave irradiation (125 8C, 0.5-2 h) the polysubstituted indole derivatives 1 n-v in 68-92 % yield (Table 1, entries 12-20). For electron-rich substrates conventional heating rather than microwave irradiation was also successful, but under these conditions the cyclization to give the indole derivatives required longer reaction times.…”

Reaction Mechanism for the LiCl‐Mediated Directed Zinc Insertion: A Computational and Experimental Study

“…Koszinowski et al detected Li + ZnRClHal À (Hal = halide), which had been proposed by Knochel as the active species for the LiCl-mediated zinc insertion, [2] in the reaction mixture by using ESI-MS. [4, 1f] However, the reaction pathway and mechanism of Li + ZnRClHal À formation are still far from being settled. Herein, we report an experimental/computational study on the LiCl-mediated zinc insertion, and we address the questions of the generation mechanism of Li + ZnRClHal À , the role of LiCl, and the origin of the regioselectivity in the reaction.…”

Fischer‐Indolsynthese mit Organozinkreagentien

“…in THF das erwartete Alkylzinkhalogenid (6 a) in 90 % Ausbeute (50 8C, 1 h). [13] Die Zugabe einer THF-Lösung von 6 a (1 ¾quiv.) zu dem funktionalisierten Aryldiazoniumtetrafluoroborat (5 a; 1.25 ¾quiv., À60 8C bis 25 8C) ergibt eine Azoverbindung des Typs 4 B, die zum ungesättigten Hydrazin 4 A isomerisiert.…”

“…11). Sekundäre Cycloalkylzinkhalogenide wie 6 e-g [12,13] addieren an funktionalisierte Aryldiazoniumsalze (5 a-g) und ergeben nach Mikrowellenbestrahlung (125 8C, 0.5-2 h) die mehrfach substituierten Indolderivate 1 n-v in 68-92 % Ausbeute (Tabelle 1, Nr. [12][13][14][15][16][17][18][19][20] …”