Stereoselective synthesis of cis and trans four‐membered cyclic nitrones

Abstract

AbstractNitroalkenes 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 trans four‐membered cyclic nitrones 12–13 upon reaction with 6. Nitroalkene 4i reacts with 6c to give a 1:1 mixture of the cis and trans 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‐azetecarboxamide 1‐oxide (13k) was elucidated by means of X‐ray analysis. Only from the reaction of 1‐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.