A facile synthesis of 2,5-disubstituted oxazoles via a copper-catalyzed cascade reaction of alkenes with azides

Abstract

A novel and efficient approach to the synthesis of 2,5-disubstituted oxazoles is developed via a 1,3-dipolar cycloaddition/ring cleavage/1,2-H migration/denitrogenation/copper-catalyzed aerobic oxidative dehydrogenative cyclization cascade. The desired products can be obtained from readily available aromatic terminal alkenes and azides employing air as the oxidant under mild conditions, and it offers an attractive alternative method for the synthesis of oxazole derivatives.

Gold‐Catalyzed Synthesis of 2,5‐Disubstituted Oxazoles from Carboxamides and Propynals

“…Under the optimized conditions, KBPh 4 , AgSbF 6 and AgNTf 2 were used as additive to check if they were better than KB(C 6 F 5 ) 4 (entry18-20). It was proved that Ph 3 PAuCl/KB(C 6 F 5 ) 4 was the best catalytic system.…”

“…In order to increase the modularity of the synthetic protocols, efficient intermolecular methods to access 2,5-substituted oxazoles are desirable. For this purpose, many metal catalysts were applied, such as copper, [4] palladium, [5] ruthenium [6] and cobalt. [7] In the field of gold catalysis [8] an elegant strategy was introduced by Zhang's group in which intermediary formed a-oxo gold carbene intermediates, generated by N-oxides, [9] were trapped by nitriles to form 2,5-disubstituted oxazoles via an intermolecular process (Scheme 1, eq.…”

Synthesis of 2,4,5-Trisubstituted Oxazoles with Complementary Regioselectivity from α-Oxoketene Dithioacetals and β-(Methylthio)-β-(het)aryl-2-propenones

“…Oxazole derivatives have also found applications in functional materials, as efficient luminophores for liquids and plastic scintillators, fluorescent probes for biological systems, corrosion inhibitors, components of laser dyes, sensors, receptors, polymers, and ligands for catalysis . This has generated considerable interest in the synthesis of this class of heterocycles in recent years with the development of several efficient synthetic methods. − …”

“…Among recently reported methods, oxidative or photocatalytic [3+2] annulations of benzylamines with prefunctionalized ketones/esters have been well studied as straightforward procedures . Other recent examples include cycloaddition of activated methylene isocyanoacetates with α-ketoacids/esters, − catalytic enantioselective α-addition of isocyanides to alkylidene malonate, Pd catalyzed imidoylative cyclization of α-isocyanoacetamides, Cu­(I) catalyzed cycloaddition of acyl azide with 1-alkynes, gold catalyzed three component annulations of benzylimines, tandem aza-Wittig reaction of acyl chloride and vinyliminophosphoranes, gold catalyzed formal [3+2] cycloadditions of N -ylides, or dioxazoles, or N -(pivalolyloxy)­amides with alkynes, catalytic asymmetric carbonyl-ene reaction of β,γ-unsaturated α-ketoesters with 5-methyleneoxazolines, photoredox catalyzed three component cyclization of 2 H -azirines, methods based on cyclization- isomerization of propargylamides, oxidative annulations of enaminoesters/ketones or amides in the presence of hypervalent iodine reagents, oxidative [2+2+1] cycloannulation of alkynes and nitriles, − and copper mediated oxidative dehydrogenative annulations of aldehydes, amines, and molecular oxygen…”

Synthesis of Substituted Oxazoles by Visible-Light Photocatalysis

“…Due to their significant importance, several methodologies have been developed to construct functionalized oxazole skeletons . In general, the motif is generated by cyclization of acyclic precursors and oxidation of oxazolines . However, there is still significant scope for the development of a single-step method from readily available starting materials under mild reaction conditions.…”