2-Isoxazolines with an electron-acceptor substituent at C(5) in reactions with nucleophilic reagents

Abstract

Depending on the substituent at position 5 of the heterocycle, reaction of 2-isoxazolines with K-selectride, molybdenum hexacarbonyl, dimsyl sodium, and butyl lithium gave 1,3-cyclodecomposition, aromatization of the isoxazoline ring, or reduction of the functional groups in the substituted isoxazolines.We described previously the reaction of 3-R-5-(4-pyridyl)-2-isoxazols with K-selectride (KBH(s-Bu) 3 ) and other organometallic reagents (butyl lithium, dimsyl sodium, and molybdenum hexacarbonyl) which occurred by decomposition of the isoxazoline ring at the N-O and C (3) -C (4) bonds to give nitriles and 4-vinylpyridine [1-4]. However, 2-isoxazolines with phenyl, 2-pyridyl, or 2-oxo-1-pyrrolidyl substituents at C (5) did not give products of cyclodecomposition in such reactions [2, 5]. Similar 1,3-cyclodecomposition under the influence of bases was known for a series of 5-acylisoxazolines and 5-nitroisoxazolines [6, 7]. Only products of 1,4-cyclodecomposition were isolated from reactions of 2-isoxazolines with metal polycarbonyls [8,9].The decomposition of the heterocycle of 2-isoxazolines at two bonds is formally the reverse of the synthesis of the heterocycle and not infrequently complicates the typical decomposition of the ring of 2-isoxazolines, which normally occurs at one of the bonds of the N-O-C unit. It is generally considered that 1,3-cyclodecomposition under the influence of bases goes via the generation of an anion at the C (5) atom of the ring [6,7,10]. However, the most acidic hydrogens are at C (3) in 3-substituted 2-isoxazolines and at C (4) in 3-unsubstituted isoxazolines [11,12]. 5-endo-Deprotonation is generally uncharacteristic but may occur when there are an electron-acceptor substituents at C (5) , capable of creating a considerable increase in the acidity of the H-5 proton and facilitating the stabilization of the anion formed.To determine the limit of the applicability of the 1,3-cyclodecomposition reaction it was expedient to compare the reactions of 2-isoxazolines, having electron-acceptor substituents at C (5) , with typical bases, on the one hand, and with nucleophilic organometallic reagents, on the other hand. The cryptobasic reducing agent K-selectride has a nucleophilic character. Molybdenum hexacarbonyl reacts with 2-isoxazolines with the intermediate formation of a vinyl-nitrene complex with delocalization of the π-d electrons from the metal into the C=N-O π-orbital of the heterocycle, which makes easy rupture of the N-O bond possible [10,13].