Toluene Synthesis Lab Report

The synthesis started with the [3+2] cycloaddition between chiral nitrone 128 and allyl cyanide under microwave activation at 110°C in toluene to provide cycloadduct 2 in 96% yield as a single isomer (Scheme 1).The regioselectivity was identical to that observed for diverse terminal alkenes, with attack on the terminal methylene by the electrophilic carbon of the nitrone, presumably due to both steric and electronic reasons.29a-f The stereoselectivity results from the approach of allyl cyanide on the less hindered face of nitrone 1 (opposite to the isopropyl group), the reaction taking place via a transition state placing the cyanomethyl group away of the spirocyclic nitrone according to an exo-approach (Scheme 1). In 1D NOE experiments with …show more content…
The combination of amidoxime 3 and various aldehydes in freshly distilled toluene under reflux for 18h in the presence of molecular sieves and a catalytic amount of p-toluenesulfonic acid (APTS) led to the formation of 3,5-disubstituted-1,2,4-oxadiazoles 4a-f in good yields (51‒70%). The acidiccleavage of the menthone chiral auxiliary30a-d in 4c-e was achieved by acetolysis, in a mixture of Ac2O/AcOH and with a catalytic amount of H2SO4. After neutralization with 5M NaOH added dropwise, the methylamide-isoxazolidines 5c-d were obtained in 60 and 57% yields, respectively, from 4c-d, while the N-acetyl-methylamide-isoxazolidine 5e was obtained in 68% yield from 4e. Acid treatment of the compound 4a led to cleavage and formation of a mixture N-acetyl-methylamide-isoxazolidine 5a and methylamide-isoxazolidine 5’a in 52 and 28% yields, respectively. Unfortunately, the acidic cleavage in compounds 4b,f provided complex mixtures of inseparable products under similar reaction conditions and the desired product 5f, obtained from 4f, could only be detected by mass spectrometry (MS (ESI, +c): m/z = 365.1