Synthesis of Isoxazoline N-Oxides via [Hydroxy(tosyloxy)iodo]benzene (HTIB)-Mediated Oxidative N−O Coupling

Abstract

An HTIB mediated oxidative N-O coupling strategy for the synthesis of some isoxazoline N-oxide derivatives from β-hydroxyketoximes is described, along with a comparative study of the efficiency of N-O coupling in two different solvents. A plausible mechanism for the conversion is proposed.

Oxidative cyclizations of oximes using hypervalent iodine reagents

“…The cyclization reactions of oximes using hypervalent iodine(III) reagents can proceed with various nucleophiles, such as alkenes, [73][74][75][76] alcohols, [77][78][79][80][81] or amines, 67,82 within the molecule to produce the respective cyclic compounds. For example, Aggarwal and co-workers have reported an efficient synthesis of 2,3-diphenylquinoxaline-1-oxides 56 from benzyl--arylimino oximes 55 using DIB (Scheme 17).…”

“…Reactions of ketoximes in which an N-O bond is formed, giving isoxazole N-oxide derivatives, have been reported. [77][78][79][80] Effective procedures for the preparation of various isoxazole N-oxides from ketoximes have been developed by several research groups. Yao and co-workers have reported the Koser's reagent-induced oxidative heterocyclization reactions of ketoximes in water or methanol producing the corresponding isoxazole N-oxides in good yields.…”

“…Yao and co-workers have reported the Koser's reagent-induced oxidative heterocyclization reactions of ketoximes in water or methanol producing the corresponding isoxazole N-oxides in good yields. 77 The reaction of bisoxime 57 with Koser's reagent in water affords benzodiisoxazole di-N-oxide 58 as the sole product in good yield (Scheme 18). The analogous iodine(III)-mediated reactions of ketoximes with amines as nucleophiles result in N-N bond formation producing the corresponding pyrazolin-5-one N-oxide derivatives.…”

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF3 Stereogenic Center

“…[26] Thereafter, the same group elaborated a strategically distinct approach for the asymmetric synthesis of chiral 5-CF 3 -2-isoxazoline 8 a via its N-oxide. [27] Building on the use of the asymmetric epoxidation adduct 2 a with the already established synthetic method by the same group, [15] the subsequent Zn/ NH 4 Cl-reduction product (R)-11 underwent an oxidative NÀO coupling reaction mediated by [hydroxyl(tosyloxy)iodo]benzene (HTIB) to form N-oxide (R)-12. The desired product (R)-8 a was generated in 96 % yield in enantiomerically pure form by a deoxygenation reaction with P(OMe) 3 .…”

ChemInform Abstract: Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a C—CF3 Stereogenic Center

“…[26] Thereafter,t he same group elaborated as trategically distinct approachf or the asymmetric synthesis of chiral 5-CF 3 -2-isoxazoline 8a via its N-oxide. [27] Building on the use of the asymmetric epoxidation adduct 2a with the already established synthetic methodb yt he same group, [15] the subsequentZ n/ NH 4 Cl-reduction product (R)-11 underwent an oxidative NÀO coupling reaction mediated by [hydroxyl(tosyloxy)iodo]benzene (HTIB) to form N-oxide (R)-12.T he desired product (R)-8a was generated in 96 %y ield in enantiomerically pure form by ad eoxygenation reactionw ith P(OMe) 3 .E nantiopurityw as not eroded in any transformation.I np arallel, an ew synthetic shortcut toward chiral alcohol (R)-11 wasc arried out with ar elatively lower ee value (78 %) through the catalytic asymmetric decarboxylative aldol reaction by using trifluoromethylated ketone 5a and b-keto acid 13 a.F inally,( R )-8a with 78 % ee was afforded by the same series of synthetic procedures as before (Scheme 6). [28]…”