ChemInform Abstract: One Pot Stereoselective Synthesis of Isoxazolines from N‐Phenyl‐α‐chloro Nitrone.

Abstract

Isoxazole derivatives R 0240One Pot Stereoselective Synthesis of Isoxazolines from N-Phenyl-α-chloro Nitrone. -(CHAKRABORTY*, B.; KAFLEY, S.; CHHETRI, M. S.; Indian J.

α-N-Methyl/Phenyl Furan Derivatives as Dipolarophiles for Synthesis of Spiro Isoxazolidine Derivatives with α-Chloro and Simple Nitrones

“…N-Phenylhydroxylamine was prepared following standard methods available in the literature and has been used already for the reported synthesis of aldehydes and in cycloaddition reactions involving α-amino, α-chloro nitrones in aqueous phase and in organic solvents. [3][4][5][6][7][8][12][13][14][15] General procedure for synthesis of aldehyde and furan derivatives 2 To a stirred solution of nitrone 1 (R=Me; 500mg, 3.0198 mmol) in dry ether (25 ml) was added pyridine (1 equivalent) and stirred at RT with a magnetic stirrer under N 2 atmosphere for 1 h while the formation of transient nitrone 1a (not isolated) was monitored by TLC (R f = 0.38). Benzyl chloride (292.mg, 1 equiv) was added at this stage and the reaction mixture was stirred for another 3 h until the intermediate compound 1b (not isolated) was developed (monitored by TLC; R f = 0.40).…”

“…In general, the reactions are very clean and high yielding compared to other cycloaddition reactions of α-chloro and α-amino nitrones. 1,[3][4][5][6][7][8][13][14][15] The products are characterised from their spectroscopic (IR, 1 H NMR, HRMS, 13 C NMR) data. No catalyst or co-organic solvent is required.…”

“…2 The synthetic potential of α-chloro nitrones (1) has been proved not only in cycloaddition reactions but also in the synthesis of novel dipolarophiles (2) when treated with alkyl halides. 3 α-N-methyl/phenyl furan derivatives (2) were isolated as side-products and in single E isomeric forms (almost 20%) in the reported oxidation reaction of alkyl halides to aldehydes and ketones using α-chloro nitrones [4][5][6][7][8] (Scheme 2). The novel 5-spiro isoxazolidines (3)(4)(5)(6)(7)(8) were predominantly obtained regioselectively in high yields (78-88%) as single isomers in the reactions of α-chloro, α-amino and simple nitrones.…”

“…3 α-N-methyl/phenyl furan derivatives (2) were isolated as side-products and in single E isomeric forms (almost 20%) in the reported oxidation reaction of alkyl halides to aldehydes and ketones using α-chloro nitrones [4][5][6][7][8] (Scheme 2). The novel 5-spiro isoxazolidines (3)(4)(5)(6)(7)(8) were predominantly obtained regioselectively in high yields (78-88%) as single isomers in the reactions of α-chloro, α-amino and simple nitrones. This could be due to the fact that the nitrone (LUMO)-dipolarophile (HOMO) interactions are strong enough to dominate the reaction [9][10][11] and lead to the formation solely of 5-spiro cycloadducts (3)(4)(5)(6)(7)(8) via an exo approach of the nitrone 1 (all the reported nitrones have a Z configuration) to the furan derivatives 2 (transition state 1).…”

“…The novel 5-spiro isoxazolidines (3)(4)(5)(6)(7)(8) were predominantly obtained regioselectively in high yields (78-88%) as single isomers in the reactions of α-chloro, α-amino and simple nitrones. This could be due to the fact that the nitrone (LUMO)-dipolarophile (HOMO) interactions are strong enough to dominate the reaction [9][10][11] and lead to the formation solely of 5-spiro cycloadducts (3)(4)(5)(6)(7)(8) via an exo approach of the nitrone 1 (all the reported nitrones have a Z configuration) to the furan derivatives 2 (transition state 1). At the outset of this work it was unclear whether the side-products obtained during aldehyde and ketone synthesis could be employed as efficient dipolarophiles.…”