Stereochemistry at trivalent nitrogen. VIII. Steric and solvent effects on slow nitrogen inversion in an isoxazolidine

A study of conformational behaviour in some hexahydro-2H-isoxazolo[2,3-a]pyridines

“…Integration of the relevant peaks gives the population trends in these systems (Tables 2 and 3). The proton spectra in toluene-d 6 and CD 3 OD were used in the calculation of the nitrogen inversion barriers in all compounds. The solvent CDCl 3 was avoided since it was found that some of the compounds deteriorated at higher temperatures (~75°C) in the halogen containing solvent.…”

“…Any increase in the barrier in cyclic system is attributed to the extra energy required for breaking of H-bonding prior to inversion. 6 The population of the cis-invertomers is higher in CD 3 OD than in CDCl 3 (Table 2) for the ioxazolidines 3a, 3b and 3c, indicating that the invertomer is more stabilized by hydrogen bonding than the trans invertomer. However, the compound 3d behaves the opposite way.…”

“…The nitrogen inversion barrier is expected to be high when an oxygen atom is directly attached to the nitrogen as in isoxazolidines. 6,7 The inversion barriers observed in the isoxazolidines 3 in toluene-d 6 are in the relatively narrow range 62.1-68.3 kJ mol -1 . This is expected since the steric requirements to attain the sp 2 hybridized transition state (through which the nitrogen inversion occurs) remains more or less similar as the substituents in the immediate vicinity of nitrogen (i.e.…”

“…3 It is often difficult to assign the configuration at various chiral centers of the cycloadducts 3 and 4 by spectroscopic analysis owing to complications arising out of slow nitrogen inversion process involving cis-and trans-fused invertomers. The presence of −N−O− moiety in an organic molecule (as in the case of isoxazolidines 3 and 4) has a distinctive place in conformational analysis [4][5][6] ; oxygen being next to nitrogen raises the barrier to nitrogen inversion to such an extent that the individual invertomers can be identified by NMR spectroscopy. 7 The previous studies 8 of nitrogen inversion have greatly contributed to the understanding of several reaction processes.…”

A study of nitrogen inversion process in some camphor-based isoxazolidines

“…1 The presence of an −N−O− moiety in an organic molecule has a distinctive place in conformational analysis, [2][3][4] oxygen being next to nitrogen raises the barrier to nitrogen inversion (N i ) to such an extent that at temperatures lower than the ambient, individual invertomers can be identified by NMR spectroscopy. 5 The asymmetric nitrone cycloaddition reactions involving camphor-derived intramolecularly H-bonded nitrone (Scheme 1) has been found to be very effective in transferring chirality to the newly created stereocenter at C(5) of the cycloadducts isoxazolidines.…”