Stereoselective synthesis of cis and trans four‐membered cyclic nitrones

Abstract

Abstract. Nitroalkenes 3-5 react with ynamines (1-aminoacetylenes) 6 to yield four-membered cyclic nitrones (2,3-dihydroazete 1-oxides) 7-13. The nitroalkenes 3 and 5c give the cis fourmembered cyclic nitrones 7-11, whereas 4 and 5b yield the truns four-membered cyclic nitrones 12-13 upon reaction with 6. Nitroalkene 4 i reacts with 6c to give a 1: 1 mixture of the cis and tram four-membered cyclic nitrones 9g and 13i. The trans stereochemistry of trans-N, N-diethyl-2,3-dihydro--3-(2-methoxynaphthalenyl)-2-methyl-4-phenyl-2-~etecarboxamide 1 -oxide (13k) was elucidated by means of X-ray analysis. Only from the reaction of I-nitrocyclopentene (5a) with 6c, the initially formed (4 + 2 ) cycloadduct, the nitronic ester 17 has been isolated. The thermal ring contraction of 17 yields 3a,4,5,6-tetrahydro-N, N-dimethyl-3-phenyl-3H-cyclopent [c]isoxazole-3-carboxamide ( 19), the structure of which was established by X-ray analysis. The trans four-membered cyclic nitrones are thermally relatively stable compared with the cis nitrones. The mechanism of the stereoselective formation of the nitrones is related to the conformation of the (4 + 2) cycloadduct 16, which could be correlated with Chem-X and MNDO calculations.

Ring Closure of Nitroalkylmalonates for the Synthesis of Isoxazolines under the Acylation Conditions

“…[13,21] Finally, pathway (d) involves the O-acylation of malonate anion F, cyclization via Michael addition (Q!R), and rearrangement of intermediate S. This route is consistent with the literature data showing some examples of rearrangement of 4H-oxazine-N-oxides of type S into isoxazolines. [22] During the previous studies we observed that mono-ester substituted nitroalkanes did not yield isoxazolines under the acylation conditions. [9] This fact underlines the importance of CH acidity of the substrate.…”

2-(Dichloromethylene)azetidines: Stable Strained Cyclic Enamines

“…2-Methyleneazetidines, as the higher homologues of the more intensively investigated 2-methyleneaziridines, 2 form a class of constrained cyclic enamines which remain rather unexplored due to their limited stability. Only 2methyleneazetidines substituted with electron-withdrawing groups at nitrogen, e.g., N-tosyl, 3 N-acyl, 4 N-alkoxycarbonyl, or N-aryl, 5 or a group which conjugates with the carbon-carbon double bond (e.g., alkoxycarbonyl, nitrile), 6 are stable. It was envisaged that, in contrast with 2methyleneazetidines unsubstituted at the double bond, 7 or with electron-donating groups at the double bond, 8 2-(dichloromethylene)azetidines bearing N-alkyl substituents would be stable.…”