Expeditious Microwave-Assisted Synthesis of 5-Alkoxyoxazoles from α-Triflyloxy Esters and Nitriles

Abstract

A rapid and general access to diversely substituted 5-alkoxyoxazoles 2 (i.e., R(1), R(2) = alkyl, phenyl) from easily accessible α-triflyloxy/hydroxy esters 1 and nitriles with good yields (41-76%) is reported. The versatility of the cyclization is shown for a range of substrates with high selectivity toward triflates over mesylates and proved to be compatible with sensitive functional groups. As an illustration of this transformation, the first synthesis of the recently isolated hydroxypyridine methyl multijuguinate 4 was achieved in four steps through a hetero Diels-Alder reaction of the 5-alkoxyoxazole and acrylic acid, followed by a protodecarboxylation reaction.

Fluorophore-Assisted Click Chemistry through Copper(I) Complexation

“…the desired product was obtained as a yellow oil (620 mg, 2.90 mmol, 67%). The 1 H RMN analysis is in agreement with the one described in the literature [33]: 1 53 mmol) in dry THF (20 mL) was added dropwise. After 15 min at 0 • C, the solution was allowed to warm at room temperature and further stirred for 3 h. Then, the mixture was cooled to 0 • C, and water (5 mL), a solution of aqueous NaOH (5 M, 5 mL), and water (15 mL) were added successively.…”

“…The fluorescent chelating agent 1 was prepared from commercial L-aspartic acid diethyl ester hydrochloride (Scheme 1). First, the reported oxazole ester 2 obtained in two steps [33], was reduced into the corresponding alcohol derivative 3 in 46% isolated yield. The hydroxyl group was then converted into mesylate intermediate 4, which was subsequently displaced with azide ion to afford compound 5 in 74% over two steps.…”

5‐Alkoxyoxazole – A Versatile Building Block in (Bio)organic Synthesis

“…Alternative protocols that involve mild and effective cyclodehydration processes instead of the traditional monomolecular Robinson–Gabriel cyclodehydration reaction, which requires harsh conditions and long reaction times, have recently emerged (Scheme , a). Other methods based on bimolecular processes include the metal‐catalyzed decomposition of α‐diazo esters 3 and 4 in the presence of nitriles and oximes, respectively (Scheme , b and c),, and a Ritter‐type reaction that involves a nitrile and α‐oxo tosylate or α‐triflyloxy ester 5 , as recently reported by Taylor and our group, respectively (Scheme , d).…”

Maleimide-based metal-free ligation with dienes: a comparative study

“…12,14 This cyclic diene was, however, isolated along with 6 % of its aromatized analog, benzyl carbamate (Figure S37), as an inseparable mixture, whatever the purification method used (normal-phase flash chromatography, RP-HPLC or recrystallization in water). These past years, our team reported the preparation of 5-ethoxyoxazole dienes from commercial αhydroxy-or α-amino esters for the total synthesis of natural compounds, [27][28][29][30] and for bioconjugation purposes. 8,31,32 Importantly, the azaphthalimide linkers generated from corresponding 5-ethoxyoxazoles revealed fluorescence behaviors, especially in aqueous media (Figure S2).…”