Kremsmair Alexander, Sunagatullina Alisa S, Bole Leonie J, Mastropierro Pasquale, Graßl Simon, Wilke Henrik R, Godineau Edouard, Hevia Eva, Knochel Paul
Department Chemie & Biochemie, Ludwig Maximilians-Universität München, Butenandtstrasse 5-13, Haus F, 81377, München, Germany.
Department für Chemie und Biochemie, Universität Bern, Freiestrasse 3, 3012, Bern, Switzerland.
Angew Chem Int Ed Engl. 2022 Oct 4;61(40):e202210491. doi: 10.1002/anie.202210491. Epub 2022 Sep 5.
A new method for regioselective zincations of challenging N-heterocyclic substrates such as pyrimidines and pyridazine was reported using bimetallic bases TMPZnX⋅LiX (TMP=2,2,6,6-tetramethylpiperidyl; X=Cl, Br). Reactions occurred under mild conditions (25-70 °C, using 1.75 equivalents of base without additives), furnishing 2-zincated pyrimidines and 3-zincated pyridazine, which were then trapped with a variety of electrophiles. Contrasting with other s-block metalating systems, which lack selectivity in their reactions even when operating at low temperatures, these mixed Li/Zn bases enabled unprecedented regioselectivities that cannot be replicated by either LiTMP nor Zn(TMP) on their own. Spectroscopic and structural interrogations of organometallic intermediates involved in these reactions have shed light on the complex constitution of reaction mixtures and the origins of their special reactivities.
报道了一种使用双金属碱TMPZnX⋅LiX（TMP = 2,2,6,6 - 四甲基哌啶基；X = Cl、Br）对具有挑战性的N - 杂环底物（如嘧啶和哒嗪）进行区域选择性锌化的新方法。反应在温和条件下（25 - 70°C，使用1.75当量的碱且无添加剂）进行，生成2 - 锌化嘧啶和3 - 锌化哒嗪，然后用各种亲电试剂捕获。与其他s - 族金属化体系不同，即使在低温下操作，它们的反应也缺乏选择性，而这些锂/锌混合碱实现了前所未有的区域选择性，这是LiTMP或Zn(TMP)单独使用时无法复制的。对这些反应中涉及的有机金属中间体的光谱和结构研究揭示了反应混合物的复杂组成及其特殊反应性的来源。
