Calculation-assisted regioselective functionalization of the imidazo[1,2- a ]pyrazine scaffold via zinc and magnesium organometallic intermediates.

Autor: Kastrati A; Department Chemie, Ludwig-Maximilians-Universität München Butenandtstrasse 5-13, Haus F 81377 München Germany zipse@cup.uni-muenchen.de knoch@cup.uni-muenchen.de., Kremsmair A; Department Chemie, Ludwig-Maximilians-Universität München Butenandtstrasse 5-13, Haus F 81377 München Germany zipse@cup.uni-muenchen.de knoch@cup.uni-muenchen.de., Sunagatullina AS; Department Chemie, Ludwig-Maximilians-Universität München Butenandtstrasse 5-13, Haus F 81377 München Germany zipse@cup.uni-muenchen.de knoch@cup.uni-muenchen.de., Korotenko V; Department Chemie, Ludwig-Maximilians-Universität München Butenandtstrasse 5-13, Haus F 81377 München Germany zipse@cup.uni-muenchen.de knoch@cup.uni-muenchen.de., Guersoy YC; Department Chemie, Ludwig-Maximilians-Universität München Butenandtstrasse 5-13, Haus F 81377 München Germany zipse@cup.uni-muenchen.de knoch@cup.uni-muenchen.de., Rout SK; Department Chemie, Ludwig-Maximilians-Universität München Butenandtstrasse 5-13, Haus F 81377 München Germany zipse@cup.uni-muenchen.de knoch@cup.uni-muenchen.de., Lima F; Global Discovery Chemistry, Novartis Institutes for BioMedical Research 4057 Basel Switzerland., Brocklehurst CE; Global Discovery Chemistry, Novartis Institutes for BioMedical Research 4057 Basel Switzerland., Karaghiosoff K; Department Chemie, Ludwig-Maximilians-Universität München Butenandtstrasse 5-13, Haus F 81377 München Germany zipse@cup.uni-muenchen.de knoch@cup.uni-muenchen.de., Zipse H; Department Chemie, Ludwig-Maximilians-Universität München Butenandtstrasse 5-13, Haus F 81377 München Germany zipse@cup.uni-muenchen.de knoch@cup.uni-muenchen.de., Knochel P; Department Chemie, Ludwig-Maximilians-Universität München Butenandtstrasse 5-13, Haus F 81377 München Germany zipse@cup.uni-muenchen.de knoch@cup.uni-muenchen.de.
Jazyk: angličtina
Zdroj: Chemical science [Chem Sci] 2023 Sep 28; Vol. 14 (40), pp. 11261-11266. Date of Electronic Publication: 2023 Sep 28 (Print Publication: 2023).
DOI: 10.1039/d3sc02893c
Abstrakt: Straightforward calculations such as determinations of p K a values and N-basicities have allowed the development of a set of organometallic reactions for the regioselective functionalization of the underexplored fused N-heterocycle imidazo[1,2- a ]pyrazine. Thus, regioselective metalations of 6-chloroimidazo[1,2- a ]pyrazine using TMP-bases (TMP = 2,2,6,6-tetramethylpiperidyl) such as TMPMgCl·LiCl and TMP 2 Zn·2MgCl 2 ·2LiCl provided Zn- and Mg-intermediates, that after quenching with various electrophiles gave access to polyfunctionalized imidazopyrazine heterocycles. Additionally, the use of TMP 2 Zn·2MgCl 2 ·2LiCl as base for the first metalation allowed an alternative regioselective metalation. Nucleophilic additions at position 8 as well as selective Negishi cross-couplings complete the set of methods for selectively decorating this heterocycle of the future.
Competing Interests: There are no conflicts to declare.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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