Regioselective C–H Activation of Substituted Pyridines and other Azines using Mg- and Zn-TMP-Bases

Abstract

The metalation of substituted pyridines, diazines and related N-heterocycles using TMPMgCl·LiCl, TMP2Mg·2LiCl, TMPZnCl·LiCl or TMP2Zn·2LiCl2·2MgCl2 (TMP = 2,2,6,6-tetramethylpiperidyl) in the presence or absence of a Lewis acid is reviewed. Contents 1 Introduction2 Magnesiation of Pyridines and Related Azines2.1 Magnesiations using TMPMgCl·LiCl2.2 Magnesiations using TMP2Mg·2LiCl and Related Bases2.3 BF3·OEt2 Promoted Metalations of Pyridines3 Zincation of Pyridines and Related Azines using TMPZnCl·LiCl and TMP2Zn·2LiCl·2MgCl2 4 Metalation of Pyridines using other TMP-Bases5 Magnesiation and Zincation of Diazines6 Conclusion

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

“…Inspired by reports of Knochel’s [19–20] and our group [21–23] on direct metalation of substituted isoquinolines at C-1 and in continuation of our recent work on the synthesis of aromatic oxoaporphine, oxoisoaporphine and pyridoacridine alkaloids [17–18 21–22] using direct ring metalations of heterocycles with the hindered amide base TMPMgCl∙LiCl as crucial step, the Knochel–Hauser base was again the metalation reagent of our choice.…”

Generation of organo-alkaline earth metal complexes from non-polar unsaturated molecules and their synthetic applications

“…[4][5][6][7][8] Deprotonative magnesiation of (hetero)arenes has also been developed for the direct preparation of arylmagnesium reagents, while it commonly needs prefunctionalization at a suitable position of the (hetero)arene substrates (Scheme 1C). 9,10 Recently, synthesis and structural characterization of various molecular magnesium(II) hydrides has successfully been achieved. 11 Employment of sterically hindered ligands (L) is the key to stabilize molecular magnesium(II) hydrides [L-Mg-H] kinetically from their Schlenk equilibrium to homoleptic magnesiumanionic ligand complexes [MgL 2 ] and insoluble magnesium hydride [MgH 2 ] n of the bulk lattice due to its higher lattice energy.…”

“… 4–8 Deprotonative magnesiation of (hetero)arenes has also been developed for the direct preparation of arylmagnesium reagents, while it commonly needs prefunctionalization at a suitable position of the (hetero)arene substrates ( Scheme 1C ). 9,10 …”

Recent Advances in Cross-Couplings of Functionalized Organozinc Reagents

“…Thus, secondary and tertiary amines of types 4 and 5 can be prepared via these electrophilic amination reactions using various functionalized organozinc reagents of type 6 (Scheme 2). Besides, we will also cover in this short review novel stereoselective cross-couplings of organozinc reagents involving stereoselective I/Li-exchange reactions 5 as well as regioselective magnesiations of N-aryl azoles and related aromatic and heterocyclic substrates 6 followed by Negishi crosscouplings after transmetalation with ZnCl2 or Cu-catalyzed cross-couplings.…”