Efficient synthesis of bridged δ-lactams from δ-bromo-2-methoxypyridine using magnesium 'ate' complexes as key reagents

摘要

Oragnic compounds with structural motif of the piperidine ring are widespread in nature and in biologically active species. In the past decade organomagnesium 'ate' complexes of the [R3Mg]Li type have attracted considerable attention as useful reagents applied in the synthesis of functionalised azaheterocycles. Among them [Bu3Mg]Li (1a) has been used as halogen-magnesium exchange reagent and lithium allyldibutylmagnesiate (1b) has beed found a powerful allylating agent. Recently, la has been also used as a base in a symmetrical double alkylation of β,γ-unsaturated lactams.In the present communication noncriogenic synthesis of δ-functionalised 2-methoxypyridines 2 via bromine-magnesium exchange reaction using la is presented. It is also demonstrated that introduction of allyl substituents into piperidine ring by addition of lb to the corresponding δ-functionalised 2-pyridones 3, optionally followed by double alkylation at C-α, leads to lactams 4, which are finally transformed to variously bridged δ-lactams 5-8 by ring closing metathesis (RCM).