A Convenient Synthetic Method of Isoxazole Derivatives Using Copper(II) Nitrate

Copper Nitrate Mediated Regioselective [2+2+1] Cyclization of Alkynes with Alkenes: A Cascade Approach to Δ2‐Isoxazolines

“…[1] Among those nitration reactions,m ost of them proceed via nitrogen dioxide radicals or via the nucleophilic attack of alkenes or aryl rings at ac ationic intermediate. [2] Although copper nitrate has been disclosed as an effective direct nitration reagent for arenes [3] and ketones, [4] theu se of this simple and inexpensive reagent as an ew and versatile nitrogen and oxygen source to replace the traditionally required agents still remains both challenging and of great value. D 2 -Isoxazoline derivatives represent an important class of five-membered heterocycles [5] and are frequently found in numerous biologically active molecules with antibacterial, [6a] antitubercular, [6b] siderophore, [6c] antidepressant, [6d] and b-galactosidase-inhibiting properties.…”

“…[11] Therefore,t he development of convenient methods for the synthesis of D 2 -isoxazoline scaffolds has invoked ever-growing synthetic efforts over the last decades. [12] Generally, D 2 -isoxazolines are prepared by 1,3-dipolar cycloaddition reactions of olefins and nitrile oxides,w hich are commonly generated in situ from substituted oximes [13] or nitro compounds [4,14] in the presence of various additives. Although these methods are often effective,s ome of them suffer from al imited scope of starting materials,n eed harsh reaction conditions,o rr equire that the substrates are employed as the solvent.…”

Synthetic Diversity from a Versatile and Radical Nitrating Reagent

“…Improvements by Itoh and Horiuchi in 2002 fast‐tracked the synthesis of isoxazolines through a one‐pot protocol from the corresponding alkene or alkyne . The reported method proceeds by means of a stoichiometric heated acidic solution of oxidative ceric(IV) ammonium nitrate with a ketone coupling partner, and was later amended with either Fe(NO 3 ) 3 or Cu(NO 3 ) 2 protocols under equally forcing conditions. These latter strategies provide the most direct access to isoxazolines but are largely hindered by low chemoselectivity.…”

“…[35] All routes requirelinear,m ulti-step, pre-functionalization,e specially for oximes, which are typically prepared under harsh conditions by at wo step-sequence with an oxime and an exogenous oxidantt os et the stage for the nitrile oxide cycloaddition.I mprovements by Itoh and Horiuchi in 2002 fast-tracked the synthesis of isoxazolines throughaone-pot protocolf rom the corresponding alkene or alkyne. [36] The reportedm ethod proceeds by meanso fastoichiometric heated acidic solution of oxidativec eric(IV) ammonium nitratew ith a ketonec oupling partner, [37] and was later amended with either Fe(NO 3 ) 3 [38] or Cu(NO 3 ) 2 [39] protocols under equally forcing conditions. These latter strategies provide the most direct access to isoxazolinesb ut are largely hinderedb yl ow chemoselectivity.…”

Copper Nitrate Mediated Regioselective [2+2+1] Cyclization of Alkynes with Alkenes: A Cascade Approach to Δ2‐Isoxazolines

“…[6e] Furthermore,t hey can also be employed as efficient chiral ligands [7] and eminent building blocks in organic synthesis as the precursors of diverse key synthetic intermediates,s uch as b-amino acids, [8] b-hydroxy ketones, [9] b-hydroxy nitriles, [10] and g-amino alcohols. [12] Generally, D 2 -isoxazolines are prepared by 1,3-dipolar cycloaddition reactions of olefins and nitrile oxides,w hich are commonly generated in situ from substituted oximes [13] or nitro compounds [4,14] in the presence of various additives. [12] Generally, D 2 -isoxazolines are prepared by 1,3-dipolar cycloaddition reactions of olefins and nitrile oxides,w hich are commonly generated in situ from substituted oximes [13] or nitro compounds [4,14] in the presence of various additives.…”