May 2023

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%.

Hydrogels with an interpenetrating polymer network (IPN) structure composed of poly(N-isopropylacrylamide) (poly-NIPAM) gel and a gel containing polyethylene glycol (PEG) chains were synthesized. They showed a typical temperature-responsive volume change in water owing to the constructed poly-NIPAM gel component. Oxidative coupling of 2-naphthol with IPN cryogels and a conventional catalyst, the CuCl2 complex of N,N,N′,N′-tetramethylenediamine, was conducted in water under an O2 atmosphere; the IPN gel prepared from PEG with a larger molecular weight of 11000 afforded a product with a good yield of 73% (91% conv.) during the reaction in basic media. The hydrogel effectively promoted the reaction but hardly produced any product without the catalyst, acting as a reactor vessel in the water. Owing to the low durability of the PEG gel component for hydrolysis, a limitation was also suggested during experiments on the recyclability of the hydrogel.

The Matteson homologation is the perfect approach for the synthesis of polyketide–peptide natural products such as the emericellamides. In only four steps, the polyketide fragment with three stereogenic centers can be obtained as a single stereoisomer. The peptide fragment is easily available via solid-phase peptide synthesis.

A short synthesis of the A-Ring of Goniodomin A was developed via radical cyclization using vinyl sulfoxide. We found that optically inactive sulfoxides are applicable to the cyclization and Pummerer rearrangement with high stereoselectivity.