Atom Efficient Magnesiation of N‐Substituted Alkyl Indoles with a Mixed Sodium‐Magnesium Base

This study presents the alkali metal mediated magnesiation (AMMMg) of three N‐alkylated indoles with the mixed Na/Mg base [(TMEDA)Na(TMP)2Mg(CH2SiMe3)] 1 (TMEDA = N,N,N′,N′‐tetramethylethylenediamine, TMP = 2,2,6,6‐tetramethylpiperidine). All three magnesiated indoles have been successfully characterised by single‐crystal X‐ray diffraction and solution state NMR studies, whereas iodolysis and Pd‐catalysed cross coupling have been investigated. The steric nature of the N‐alkyl group changes the reactivity and efficiency of 1 to give either atom efficient disodium tetraindol‐2‐ylmagnesiates [(Na‐TMEDA)2Mg(α‐C9H8N)4] 2 and [(Na‐TMEDA)2Mg(α‐C10H11N)4] 3, or [(TMEDA)Na(TMP)(α‐C11H12N)Mg(TMP)] 4, whereby only one indole molecule is selectively deprotonated. Alkali‐metal‐mediated magnesiation has been applied to a series of N‐substituted indoles. The reactive intermediates have been structurally characterised, and their potential use in both in situ iodolysis and Pd‐catalysed cross‐coupling reactions have been explored. The identity of the directing group affected the atom efficiency found.