Organic Synthesis, Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
J Org Chem. 2011 Aug 19;76(16):6670-7. doi: 10.1021/jo201009m. Epub 2011 Jul 20.
Selective bromine-magnesium exchange on 2-benzyl-5-bromo-4-methoxypyridazin-3(2H)-one could be achieved when MesMgBr was used as reagent. With more nucleophilic RMgCl species (R = Bu, i-Pr, Ph) both nucleophilic addition-elimination at C-4 and bromine-magnesium exchange at C-5 occurred. In 2-benzyl-5-bromopyridazin-3(2H)-one, which does not contain a substituent at C-4, addition could not be suppressed. Less nucleophilic Mg amides (TMPMgCl·LiCl) allowed regioselective C-H magnesiation at the C-4 position in such substrates, as exemplified for 2-benzyl-5-chloro- and 2-benzyl-6-chloropyridazin-3(2H)-one. Quenching of the magnesiated pyridazinones with electrophiles gives access to a variety of hitherto unknown pyridazin-3(2H)-one derivatives.
当使用 MesMgBr 作为试剂时，可以在 2-苄基-5-溴-4-甲氧基哒嗪-3(2H)-酮上实现选择性溴-镁交换。当使用更亲核的 RMgCl 物种（R = Bu、i-Pr、Ph）时，C-4 上的亲核加成-消除和 C-5 上的溴-镁交换都会发生。在 2-苄基-5-溴哒嗪-3(2H)-酮中，由于 C-4 上没有取代基，因此不能抑制加成反应。在这些底物中，亲核性较弱的 Mg 酰胺（TMPMgCl·LiCl）允许在 C-4 位置进行区域选择性 C-H 镁化，例如 2-苄基-5-氯-和 2-苄基-6-氯哒嗪-3(2H)-酮。用亲电试剂淬灭镁化的哒嗪酮可以得到各种以前未知的哒嗪-3(2H)-酮衍生物。
