Abstract
The synthesis of eight pyridine-oxazoline ligands, five of which have never been reported
previously, is described. The ligands were prepared in two efficient steps, initially
preparing 2-pyridyl alkylnitriles, followed by their conversion into oxazolines ligands
using chiral amino alcohols and zinc chloride. The 2-pyridyl nitriles are prepared
via a novel SNAr alkylation reaction of 2-bromopyridine with alkyl nitriles using methylmagnesium
chloride as a non-nucleophilic base in conjunction with an amine mediator. This methodology
allows preparation of the existing gem-dimethyl motif and its elaboration beyond previously prepared ligands in fewer steps
with simplicity and scalability. The toleration of variation in the nitrile, halopyridine,
and amino alcohol starting materials allows for other novel bridging substitution
which gives new ligands with enhanced reactivity. The library of bridging ligands
was applied to the Pd-catalysed allylic alkylation of 1,3-diphenylprop-2-enyl acetate
with dimethyl malonate and afforded conversions of up to 100% and enantioselectivities
of up to 68%.
Key words
nitriles - S
NAr alkylation - Grignard reaction - pyridine oxazoline - zinc chloride